Methylation of the suppressor of Cytokine Signaling 1 Gene (SOCS1) in Philadelphia-negative myeloproliferative neoplasms.

OBJECTIVE: Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation is initiated by mutations in the JAK2 gene. This activation is in turn, a vital pathogenetic mechanism in myeloproliferative neoplasms (MPNs). However, several factors affect the pathogenesis of MPNs other than the JAK2 gene mutations, such as the downregulation of cytokine signaling (SOCS) proteins, which are potent inhibitors of the JAK/STAT pathway. Therefore, we hypothesized that the regulation of SOCS protein system might be a possible pathogenetic mechanism of MPNs through activating the JAK/STAT pathway. PATIENTS AND METHODS: Our study aimed to investigate the status of the Suppressors of cytokine signaling 1 (SOCS1) in 125 MPNs specimens at the level of mutated points. The acquired mutations, aberrant expression, and/or CpG island hypermethylation of SOCS1 were analyzed among Philadelphia-negative myeloproliferative neoplasm patients. RESULTS: SOCS1 was identified in 20.0% of all patients with Philadelphia-negative myeloproliferative neoplasm. At the diagnosis, the prevalence of methylation was 41.0% for Polycythaemia Vera (PV), 27.7% for Essential Thrombocythaemia (ET), and 6.6% for Primary Myelofibrosis (PMF). The methylation was not detected in 20 healthy adult people. A significant association was found between disease groups (p=.077). The presence of methylated SOCS1 was found to be significantly correlated with age (p=.005), total RBCs count (p=.019), hemoglobin (Hb) concentration (p=.002), and Hematopoietic cell transplant (HCT) (p=.007) in PV patients. However, the presence of methylated SOCS1 was found to be significantly associated with age (p=.012), total RBCs count (p=.022), Hb concentration (p=.024), HCT (p=.033), and platelets count (p=.037) in ET patients. Moreover, the presence of methylated SOCS1 was significantly associated with Hb concentration (p=.046) and HCT (p=.040) in PMF patients. CONCLUSIONS: We concluded that the activation of the JAK/STAT signaling pathway in alternative or with JAK2 mutations leads to SOCS1 hypermethylation, which could represent a potential therapeutic target.

[Recommendations on organization, design, characteristics and operation of neonatology services]. / Recomendaciones de organización, diseño, características y funcionamiento de servicios o unidades de neonatología.

Neonatal care has undergone important advances involving the technology for treatment and mo nitoring, the design of care spaces, the incorporation of support professionals, and, especially, the strengthening of an organizational model in networks with centers of different levels of care. Neona tal units should be located in centers with maternity services and, ideally, with pediatric ones of an equivalent level of care. This document defines the admission and transfer criteria according to the level of care and among the different levels, respectively. The evidence recommends an individual room design due to the associated benefits such as decreased occurrence and better control of health care-associated infections, improved breastfeeding, and better interaction with parents. The sugges ted room sizes favor the implementation of the family-centered care model. These recommendations establish the possibility of performing emergency surgical procedures in the neonatal unit and define the safety criteria of the physical plant. In addition, they define the human resources according to the level of care, recognizing the time dedicated to non-direct patient care activities, , and the re quirements of non-medical professionals such as psychologists, physical and respiratory therapists, occupational therapists, speech therapists, pharmacists, dietitians, and social workers. Neonatal care should be led by the neonatologist allowing the participation of general pediatricians with training and demonstrated experience in neonatal care. Midwives and neonatal nurses should have accredited formation in such area. The purpose of this document is to update the "Recommendations on the Organization, Characteristics and Operation of Neonatology Services or Units" to serve as an orien tation and guide for the design and management of neonatal care in public and private health care centers in the country.

Síndrome hipotónico del recién nacido / Hypotonic syndrome in the newborn

Background: The Newborn Hypotonic Syndrome (NHS) is a clinical entity that presents up to 28 days after birth. The main symptom is a significant decrease in muscular tone, but its severity is determined by the lack of muscular strength. NHS is a relatively frequent entity, so it becomes an important diagnosis problem. There is few information in literature regarding its incidence. Method: Retrospective study performed between May 2000 - April 2006, including patients with diagnosis of NHS in a Neonatal Intesive Care Unit. Results: 2 158 newborns, of which 113 (5.2 percent) had NHS. 83 percent of cases were attributed to central causes, such as hipoxic-isquemic encephalopathy (49 percent) and genetic disorders (15 percent). 17 percent of cases corresponded to peripheral causes, including hypermagnesemia (68 percent) and myopathic diseases (21 percent). Conclusions: 1) NHS is a relatively frequent clinical entity; 2) Central causes are the most prevalent; 3) It is possible to study the etiology of NHS with a systematic approach.

Introducción: El síndrome hipotónico del recién nacido (SHRN) es un cuadro clínico que se presenta hasta los 28 días de vida extrauterina. Su síntoma definitorio es la disminución significativa en tono muscular, pero su gravedad se relaciona a asociación a falta de fuerzas. Es un cuadro aparentemente poco frecuente en este grupo etáreo, pero que plantea un problema diagnóstico importante. Existe escasa información en la literatura respecto a su frecuencia real. Objetivo: Evaluar la incidencia de SHRN, su etiología y aprobación diagnóstica. Método: Estudio retrospectivo con revisión de fichas clínicas, desde mayo 2000 a abril 2006, incluyendo pacientes ingresados con diagnóstico de SHRN a unidad de intermedio-intensivo de servicio de recién-nacidos de un hospital universitario (SRNU). Resultados: El número total de RN ingresados a SRNU fue 2158, en 5,2 por ciento (113) el motivo de ingreso, principal o secundario, correspondió a SHRN. Del total de SHRN, 83 por ciento correspondió a causas centrales, destacando encefalopatía hipóxico-isquemica (ehi) (49 por ciento) y genetopatía (15 por ciento). Las causas periféricas correspondieron a 17 por ciento, destacando hipermagnesemia (68 por ciento) y miopatías (21 por ciento). Conclusiones: Con los datos obtenidos, es posible concluir para este estudio: 1) El SHRN es una entidad clínica relativamente frecuente; 2) Las causas centrales son las más frecuentes; 3) Es posible estudio escalonado orientado a encontrar etiología específica del SHRN.

Oxigenación con membrana extracorpórea en pacientes pediátricos: Comunicación de los 3 primeros casos tratados / Extracorporeal membrane oxygenation (ECMO): Consolidation of a neonatal-pediatric program in Chile and report of three cases

Extracorporeal membrane oxygenation (ECMO) improves survival in neonatal and pediatric patients with reversible severe respiratory or cardiac failure, in whom intensive treatment fails. Since 1999, a multidisciplinary team is trained to form the first neonatal-pediatric ECMO center in Chile, according to the norms of the Extracorporeal Life Support Organization (ELSO). During 2003 the first three patients were admitted to the program: a male newborn with pulmonary hypertension, a 38 days old female operated for a total anomalous pulmonary venous connection and a 3 months old male with a severe pneumonia caused by respiratory syncytial virus. They remained in ECMO for five, seven and nine days respectively and all survived to the procedure. No neurological complications were observed after one and a half year of follow up. This consolidates the first national neonatal-pediatric ECMO program, associated to ELSO. Up to date, twelve patients have been admitted to the program.

Tratamiento de la asfixia perinatal con hipotermia corporal total (caso clínico) / Treatment of perinatal asphyxia with total body hypothermia: a clinical case

El manejo del RN de termino asfixiado, ha mejorado gracias a la mayor disponibilidad de terapia intensiva, sin embargo, es poco lo que se ha progresado en su neuroprotección. Caso clínico: Recién nacido (RN) gravemente asfixiado, sometido a hipotermia corporal total. Madre de 38 años, diabética, inducida a las 38 semanas, desarrolla signos de sufrimiento fetal agudo. Se extrae un recién nacido con un peso de 4.545 g. Apgar 1-3-5. Requiere intubación y ventilación mecánica por apnea, un gas arterial a los 30 min muestra acidosis metabólica severa. A las 2 h de vida presenta signos de encefalopatía hipóxica isquémica grave y depresión difusa del voltaje en el electroencefalograma. Se somete a hipotermia corporal total a una temperatura rectal de 33° C a 34° C, durante 72 h no hubo efectos colaterales importantes. Se da de alta a los 10 días en buenas condiciones neurológicas. El seguimiento se realiza por 2 años. El test de Bailey da un puntaje de 82 en la escala motora y 95 en la escala mental. Este caso demuestra que este tipo de tratamiento es factible de realizar, si se selecciona adecuadamente al paciente, se inicia precozmente y cuentan con las condiciones de equipamiento y enfermería especializadas.

Epignathus: reporte de un caso y revisión de la literatura / Epignathus: a case report and review of the literature

Epignathus es una forma infrecuente de teratoma de localización orofaríngea que protruye por la boca y se asocia a una alta tasa de mortalidad causada por obstrucción severa de la vía aérea en el período neonatal. La clave del éxito del manejo de la obstrucción es a través del diagnóstico prenatal precoz y la ejecución controlada del EXIT (ex-utero intrapartum treatment), procedimiento utilizado para asegurar la vía aérea fetal. Describimos un caso de epignathus gigante y la aplicación del EXIT para el manejo de la vía aérea a través de la preservación del intercambio gaseoso uteroplacentario.

Steroid therapy for idiopathic retroperitoneal fibrosis: dose and duration.

PURPOSE: Idiopathic retroperitoneal fibrosis is an uncommon disease of unknown etiology that may involve the ureters and other retroperitoneal structures. Surgical ureterolysis as well as medical treatment with steroids have been used to treat these patients. However, there is no agreement as to the dose and duration of steroid. We adopted a regimen of long-term steroid use in this prospective study. MATERIALS AND METHODS: We treated 12 patients with idiopathic retroperitoneal fibrosis with a regimen of steroids during a 10-year period. Tissue diagnosis was established by biopsy of all lesions and ureteral obstruction was managed with insertion of a nephrostomy tube or a ureteral stent. The initial dose of prednisolone was 60 mg. on alternate days for 2 months and was tapered during the following 2 months to a daily dose of 5 mg. The total duration of prednisolone use was 2 years. RESULTS: Of the 12 patients 11 who completed this treatment regimen have been followed for a duration of 26 to 132 months (median 63.1) after discontinuation of treatment. Good response in the form of relief of symptoms and regression of the mass occurred in 9 cases and there were 2 failures. In 1 case the retroperitoneal mass did not regress and surgical ureterolysis was required. In the 2nd case symptoms recurred after discontinuation of steroid and a further small dose of steroids was required. Function deteriorated in 1 of 19 functioning renal units. No steroid related serious side effects developed. CONCLUSIONS: This regimen of steroid may be used as the primary mode of treatment for the majority of patients with idiopathic retroperitoneal fibrosis with minimal complications. Patients with idiopathic retroperitoneal fibrosis should be followed periodically for the rest of their lives.

Hernia diafragmática congénita: frontera entre ciencia básica y clínica / Congenital diafragmatic hernia: the frontier between basic and clinical science

El recién nacido con hernia diafragmática congénita (HDC) representa hoy un gran reto. La herniación precoz de vísceras como el hígado, antes de las 24 semanas de gestación provoca hipoplasia pulmonar severa, incompatible con la vida. Esto ha motivado a investigar las señales moleculares que modulan la hipoplasia pulmonar y a desarrollar nuevas terapias in utero. El modelo más usado en investigación es el modelo de HDC inducido por nitrofen en ratas. Este modelo ha permitido el estudio de factores de crecimiento, mediadores de óxido nítrico y endotelina, surfactante, cofactores y el estudio de los efectos de la oclusión traqueal in utero, tanto en el parénquima como en la vasculatura pulmonar. El factor de crecimiento de fibroblastos (FGF) aparece como factor de crecimiento destacado para el desarrollo del parénquima pulmonar, mientras que el factor de crecimiento vascular endotelial (VEGF), endotelina-1 y sus receptores son importantes para el desarrollo vascular en HDC. Para recién nacidos con HDC de alta mortalidad se han ideado protocolos de intervención in utero. Los intentos de corrección completa in utero fracasaron, pero la investigación básica respaldó el uso de técnicas de oclusión traqueal en fetos humanos. Tanto en animales como en fetos humanos se ha demostrado que la oclusión traqueal produce un dramático crecimiento pulmonar y que su vasculatura pulmonar regresa a lo normal. Actualmente se están evaluando estas técnicas de oclusión traqueal in utero por vía endoscópica mediante estudios clínicos controlados en fetos con un riesgo de morir cercano al 100 por ciento. Factores de crecimiento como VEGF y FGF serían buenos candidatos para terapia génica in utero. Quizás en el futuro, la combinación de oclusión traqueal y terapia génica in utero puedan dar un nuevo enfoque al manejo de esta devastadora enfermedad

The impact of internal spermatic artery ligation during laparoscopic varicocelectomy on recurrence rate and short post operative outcome.

OBJECTIVE: To prospectively compare the recurrence rate and short postoperative outcome after randomized laparoscopic varix ligation with internal spermatic artery (ISA) preservation versus laparoscopic varix ligation with ISA ligation. MATERIAL AND METHODS: Twenty-five patients with 35 varicocele who required varix ligation for infertility in 13 patients, scrotal pain in 15 patients and scrotal swelling in 2 patients who underwent one of two procedures: laparoscopic varix ligation with ISA prservation (Group A) or laparoscopic varix ligation with ISA ligation (Group B) were postoperatively evaluated for short post operative outcome and underwent percutaneous spermatic venograms to detect recurrence. Fisher's Exact Test was used for statistical analysis. RESULTS: Recurrence through parallel collaterals was noted in 39% and 5.9% in Group A and Group B respectively as demonstrated on percutaneous spermatic venous venography (PSV) (statistically significant p = 0.0408). Preoperative pain completely resolved in all patients in Group B and persisted in 45% in Group A. However, this was not statistically significant (p = 0.088). No testicular atrophy or hydrocele formation was noted in either group. CONCLUSIONS: Laparoscopic varix ligation with ISA ligation has lower recurrence rate than laparoscopic varix ligation without ISA ligation and may provide better varicocele related pain control with no increase in hydrocele or testicular atrophy rate. We recommend ISA ligation routinely during laparoscopic varix ligation.

Prostatic carcinoma: a nutritional disease? Conflicting data from the Kingdom of Saudi Arabia.

PURPOSE: The incidence of prostate cancer in Saudi Arabia has been reported to be low at 1.4 to 2.1/100,000 person-years. We prospectively evaluated the true incidence of this disease and its association with dietary factors. MATERIALS AND METHODS: From 1994 to 1997 inclusive Saudi men older than 50 years treated at our institution for various presenting symptoms and diseases were randomly selected from various departments. They were examined prospectively with digital rectal examination, and total and free prostate specific antigen measurement. Transrectal ultrasound and prostatic biopsy were performed when either test was abnormal. Nutrition questionnaires and detailed interviews with a nutritionist were completed to assess the type of diet, and amount of saturated and polyunsaturated fat consumption of patients with prostatic carcinoma and controls. RESULTS: For the 2,270 Saudi men screened we noted an incidence of 3.1/100,000 person-years. Our nutritional survey revealed that recent fat consumption was greater than 120 gm. per person daily, of which about 40% was from meat and dairy products. Saturated fat comprised about 50% of the total fat intake. There was no difference in the amount of fat in the diet of men with and without prostatic carcinoma. CONCLUSIONS: The incidence of prostatic carcinoma in the Kingdom of Saudi Arabia is low despite a high saturated fat diet in recent years. This finding contradicts most western clinical studies, which indicate a positive association of a high fat diet with prostatic carcinoma.

Prospective phase II trial of alternating intravesical Bacillus Calmette-Guérin (BCG) and interferon alpha IIB in the treatment and prevention of superficial transitional cell carcinoma of the urinary bladder: preliminary results.

BACKGROUND AND OBJECTIVE: Evaluate the efficacy and toxicity of alternating intravesical instillation of Bacillus Calmette-Guerin(BCG) and Interferon alpha2-b (IFN) in the treatment and prevention of recurrence of superficial transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Patients with Ta, T1 tumors and carcinoma in situ, either recurrent (TaG1, T1G1) or primary/recurrent TaG2 TaG3, T1G2, T1G3 and Tis (T: Tumor stage, G: grade) are eligible. All patients received intravesical BCG 81 mg on Weeks 1, 3, 5 and 7 and IFN 100 million units on Weeks 2, 4, 6 and 8. Cystoscopy performed 4 weeks after completion of therapy, and every 3 months thereafter. RESULTS: There was a total of 37 patients. Thirteen had TaG2, 13 T1G2, 1 T1G1, 4 TaG1, 1 TaG3, 3 T1G3 and 7 Tis (5 concurrent with other above tumors). Index lesion cleared in 7/10 patients. With a median follow-up of 26.2 month, 22 patients (59%) failed above therapy. Median time to treatment failure was 7 months. Seven, 6 and 9 patients recurred at a higher, lower and same stage or grade respectively. No grade 3 or 4 toxicity was encountered. CONCLUSIONS: Alternating intravesical BCG and IFN is effective and well tolerated therapy for superficial TCC of urinary bladder.

Incidence and pattern of varicocele recurrence after laparoscopic ligation of the internal spermatic vein with preservation of the testicular artery.

OBJECTIVES: To determine the incidence and pattern of recurrence of varicocele after laparoscopic internal spermatic vein ligation with testicular artery preservation. METHODS: In a prospective study, 16 patients who underwent 20 laparoscopic varix ligation were evaluated postoperatively for recurrence by clinical physical examination and percutaneous spermatic venography. RESULTS: No significant complications were encountered with the surgical or radiological procedure. Clinical recurrence was detected by physical examination in 20% of cases, while percutaneous spermatic venography detected recurrence in 45% of cases. The sensitivity and specificity of clinical physical examination for detecting varicocele recurrence was 33% and 90.9%, respectively with an accuracy rate of 65%. Recurrences were through parallel collaterals or medial transverse collaterals in 88.8% and 11.2%, respectively. Parallel collaterals joined the spermatic vein in mid or high retroperitoneum in seven patients while it joined the renal vein in one patient. There were no low retroperitoneal parallel collaterals. CONCLUSIONS: Laparoscopic ligation of internal spermatic vein with preservation of testicular artery is a procedure that is associated with low morbidity and quick recovery. It is able to achieve its surgical objective in only 55% of cases, however. Such information should be taken into consideration during patient counselling when selecting the operative technique of choice for varicocele ligation.

Maternal urological injuries associated with vaginal deliveries: change of pattern.

Injury to the maternal lower urinary tract is related to the standard of obstetric care and to different techniques utilized in delivery. In comparison with operative delivery, maternal urinary tract injury in association with vaginal delivery had always been exceptionally rare. However, with the recent progress in obstetric care and the introduction of new concepts such as vaginal delivery after caesarian section (VDAC), the pattern of maternal urological injuries associated with vaginal deliveries might have changed. In a retrospective study it was found that significant injuries to the lower urinary tract occurred in seven females in the course of vaginal delivery in the period between 1992 and 1994 in two major hospitals in the Riyadh area. These included rupture of the posterior bladder wall, trigone and bladder neck. Distal ureteric and urethral injuries, as well as bladder contusion were also encountered. Two patients developed vesico-uterine and vesico-vaginal fistulas. History of previous caesarian section was present in 4 patients. All deliveries were with cephalic presentation and six patients received oxytocin for induction or acceleration of labour. Episiotomy was done in 6 patients and instrumental delivery was performed in 3 patients. Gross haematuria immediately after delivery was the most common presentation, followed by urinary incontinence. Flank pain and fever were associated with ureteric injury and were delayed for few days. Urological injury should be suspected after vaginal delivery in females with previous caesarian section, if instrumental delivery is applied, and in patients with deep vaginal tears. The presence of gross haematuria, incontinence and flank pain should indicate full urological evaluation.

Bacteremia por kingella kingae en una prescolar / Kingella kingae bacteremia in a preschool girl

Se reporta por primera vez en el país una bacteremia causada por K. kingae en un paciente pediátrico, con evolución favorable. Se revisa la literatura respecto a las expresiones clínicas de K. kingae y las características microbiológicas que permiten su aislamiento e identificación enunciándose recomendaciones para optimizar su estudio

Immediate recurrence of simple renal cyst after laparoscopic unroofing.

A large simple cyst arising from the lower pole of the left kidney was unroofed with a laparoscopic transperitoneal approach, but was seen to recur in the immediate postoperative period. The possible causes of this recurrence and the limitations of the laparoscopic procedure are discussed. Technical modifications are recommended in order to reduce the risk of recurrence.

Double-blind randomized crossover study comparing intracorporeal prostaglandin E1 with combination of prostaglandin E1 and lidocaine in the treatment of organic impotence.

OBJECTIVES: To study the efficacy of lidocaine 1% in relieving pain associated with intracorporeal prostaglandin E1 and to assess its effect on the pharmacological erection. METHODS: Twenty-two patients who had previously experienced pain with intracorporeal prostaglandin E1 injections were submitted to a double-blind randomized crossover study to evaluate comparatively the effects of intracorporeal prostaglandin E1 alone and in combination with lidocaine. The signed rank test was used for statistical analysis of the results. RESULTS: With prostaglandin E1 monotherapy (20 micrograms) 86.3% of patients experienced pain and 27.2% had an adequate erection. With combination therapy (prostaglandin E1 20 micrograms plus lidocaine 1% 1 cc) 45.4% of patients experienced pain and 57.8% of patients had improvement of pain compared with prostaglandin E1 monotherapy. The adequate erectile response rate with combination therapy was 63.6%; in addition, 31.8% of patients noted enhancement in the duration of erection. The signed rank test was significant for the pain response (P < 0.01) and for the degree of erection (P < 0.01). The signed rank test was not, however, significant for the increase in duration of erection after combination therapy. No significant side effects were noted after either injection. CONCLUSIONS: Lidocaine 1% can be safely and usefully combined with intracorporeal prostaglandin E1 in the treatment of erectile dysfunction with alleviation of pain and enhancement of erectile effect.

Spermatic cord torsion in adults.

A five year retrospective review of 15 cases of spermatic cord torsion in male patients 18-years or older was performed. Eighty percent of patients were correctly diagnosed at time of initial presentation while 20% of patients were misdiagnosed as epididymitis. Fifty three percent of cases has history of similar previous attacks. The average delay prior to presentation was 7 hours. Absence of fever was the rule occurring in all patients. Leucocytosis and significant pyuria were commonly encountered occurring in 33% and 27% of patients respectively. Our orchidectomy rate was 20%. Our data suggest that while, in adult patients presenting with scrotal pain, the absence of pyuria make the diagnosis of epididymitis unlikely as a cause of the condition, the presence of significant pyuria even if associated with leucocytosis does not exclude spermatic cord torsion and further studies with Doppler examination and Radionuclide Scans are necessary to establish the diagnosis.