Perspectives in Pediatric Pathology, Chapter 6. Male Undermasculinization.

Normal male development requires three conditions: (1) adequate differentiation of the fetal testis; (2) synthesis and secretion of testicular hormones; and (3) effective action of these hormones on target organs. This requires the combined action of the inhibitory anti-müllerian hormone (AMH, secreted by Sertoli cells) to block the development of the uterus and fallopian tubes from the müllerian duct, together with the trophic stimulus of testosterone (a Leydig cell product), which leads to virilization of the wolffian ducts. Additionally, the development of external genitalia depends on the conversion of testosterone to dihydrotestosterone by the enzyme 5-α-reductase.

Perspectives in Pediatric Pathology, Chapter 20. Adolescent Varicocele.

Varicocele is characterized by elongation, dilatation, and tortuosity of the veins draining the testis and its covers, causing circulatory reflux along the inner spermatic vein [ 1 ]. Varicocele results in progressive testicular lesions and, if untreated, can lead to testicular atrophy [ 2 ]. Varicocele is considered the most frequently identified cause of male infertility [ 3 ].

Perspectives in Pediatric Pathology, Chapter 5. Gonadal Dysgenesis.

One of the most challenging areas in pediatric testicular pathology is the appropriate understanding and pathological diagnosis of disorders of sexual development (DSD), and in particular, the issue of gonadal dysgenesis. Here we present the main concepts necessary for their understanding and appropriate classification, with extensive genetic correlations.

Essential requirements for setting up a stem cell processing laboratory.

The Graft Processing subcommittee of the Worldwide Network for Blood and Marrow Transplantation wrote this guideline to assist physicians and laboratory technologists with the setting up of a cell processing laboratory (CPL) to support a hematopoietic stem cell transplant program, thereby facilitating the start-up of a transplant program in a new location and improving patient access to transplantation worldwide. This guideline describes the minimal essential features of designing such a laboratory and provides a list of equipment and supply needs and staffing recommendations. It describes the typical scope of services that a CPL is expected to perform, including product testing services, and discusses the basic principles behind the most frequent procedures.

Non-microfluidic methods for imaging live C. elegans.

There are many challenges to live Caenorhabditis elegans imaging including the high motility of the animals and sustaining their viability for extended periods of time. Commonly used anesthetics to immobilize the C. elegans for imaging purpose prevents feeding of the animals and can cause cellular physiologic changes.

Mysteries of α1-antitrypsin deficiency: emerging therapeutic strategies for a challenging disease.

The classical form of α1-antitrypsin deficiency (ATD) is an autosomal co-dominant disorder that affects ~1 in 3000 live births and is an important genetic cause of lung and liver disease. The protein affected, α1-antitrypsin (AT), is predominantly derived from the liver and has the function of inhibiting neutrophil elastase and several other destructive neutrophil proteinases. The genetic defect is a point mutation that leads to misfolding of the mutant protein, which is referred to as α1-antitrypsin Z (ATZ).

Interval exercise training in cystic fibrosis -- effects on exercise capacity in severely affected adults.

The aims of the present study were to investigate the effects of IT on lung function power (P) and oxygen uptake (VO2) at peak performance (peak) and ventilatory anaerobic threshold (VAT) in CF patients who were unable to participate in a standard exercise program (SEP) and to compare these IT responses with corresponding effects in CF patients performing SEP. 20 patients (FEV1 25.5 ± 7.

Innate immune signaling in the pathogenesis of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a challenging disease to treat, and caring for patients afflicted by it remains both frustrating and difficult. While NEC may develop quickly and without warning, it may also develop slowly, insidiously, and appear to take the caregiver by surprise. In seeking to understand the molecular and cellular processes that lead to NEC development, we have identified a critical role for the receptor for bacterial lipopolysaccharide (LPS) toll like receptor 4 (TLR4) in the pathogenesis of NEC, as its activation within the intestinal epithelium of the premature infant leads to mucosal injury and reduced epithelial repair.

PanIN-specific regulation of Wnt signaling by HIF2α during early pancreatic tumorigenesis.

Hypoxia promotes angiogenesis, proliferation, invasion, and metastasis of pancreatic cancer. Essentially, all studies of the hypoxia pathway in pancreatic cancer research to date have focused on fully malignant tumors or cancer cell lines, but the potential role of hypoxia inducible factors (HIF) in the progression of premalignant lesions has not been critically examined. Here, we show that HIF2α is expressed early in pancreatic lesions both in human and in a mouse model of pancreatic cancer.

Mechanisms of gut barrier failure in the pathogenesis of necrotizing enterocolitis: Toll-like receptors throw the switch.

Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal causes in premature infants, and its overall survival has not improved in the past three decades. While the precise cause of NEC remains incompletely understood, we and others have shown that a major predisposing factor in the development and propagation of NEC is a breakdown of the intestinal barrier which leads to bacterial translocation and systemic sepsis. In seeking to identify the causes involved, we and others have also determined that activation of the receptor for bacterial endotoxin, namely toll-like receptor 4 (TLR4), is required for the development of intestinal barrier failure leading to NEC.

Smad signaling pathways regulate pancreatic endocrine development.

Expansion of the pancreatic endocrine cell population occurs during both embryonic development and during post-natal pancreatic growth and regeneration. Mechanisms of the expansion of endocrine cells during embryonic development are not completely understood, and no clear mechanistic link has been established between growth of the embryonic endocrine pancreas and the islet cell replication that occurs in an adult animal. We found that transforming growth factor-beta (TGF-β) superfamily signaling, which has been implicated in many developmental processes, plays a key role in regulating pancreatic endocrine maturation and development.

Chronic granulomatous disease presenting as aseptic ascites in a 2-year-old child.

Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency syndrome that results from abnormal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function. This defect leads to recurrent catalase-positive bacterial and fungal infections as well as associated granuloma formation. We review the case of a 2-year-old boy who presented with ascites and fever of an unknown origin as manifestations of CGD.

Midterm survival of infants requiring postoperative extracorporeal membrane oxygenation after Norwood palliation.

This study reports the mid-term survival for neonates undergoing extracorporeal membrane oxygenation (ECMO) after Norwood palliation at a single center. Limited data exist on the mid-term survival of patients undergoing ECMO after Norwood palliation. We reviewed our ECMO experience from July 1994 to October 2008 and compared two groups: patients who required ECMO after Norwood palliation and patients who underwent Norwood palliation without ECMO.

Relationship between the electromyographic activity of the paratubal muscles and eustachian tube opening assessed by sonotubometry and videoendoscopy.

Objective: To determine the role played by the tensor veli palatini and levator veli palatini muscles (mTVP and mLVP, respectively) in eustachian tube (ET) opening.

Design: Prospective study.

Setting: Research laboratories at a tertiary care hospital.

Development of an algorithm for the diagnosis of otitis media.

Background: The relative importance of signs and symptoms in the diagnosis of otitis media has not been adequately evaluated. This has led to a large degree of variation in the criteria used to diagnose otitis media, which has resulted in inconsistencies in clinical care and discrepant research findings.

Methods: A group of experienced otoscopists examined children presenting for primary care.

Discontinuation of prolonged infusions of dexmedetomidine in critically ill children with heart disease.

Purpose: To describe changes in hemodynamic variables, sedation, and pain score after discontinuation of prolonged infusions of dexmedetomidine in a pediatric population of critically ill cardiac patients.

Methods: Retrospective case series of patients who received continuous infusions of dexmedetomidine for longer than 3 days in a pediatric cardiac intensive care unit from 2008 to 2010.

Results: Sixty-two patients, age 5.

Cytomegalovirus infection in pediatric immunocompromised hosts.

Disease caused by cytomegalovirus (CMV) infection can clinically manifest in a variety of ways in the immunodeficient host and lead to significant morbidity and mortality. Infections can be primary, occur as a result of reactivation of latent virus, or infection with a new strain of CMV. Cell-mediated immunity is the main defense against CMV disease.