Solitary iliac branch endoprosthesis placement for iliac artery aneurysms.

BACKGROUND: Isolated iliac artery aneurysms (IAAs), accounting for 2% to 7% of all abdominal aneurysms, are often treated with the use of iliac branched endografts. Although outside the manufacturer's instructions for use, iliac branched devices can be used solely, without the adjunctive placement of an endovascular aneurysm repair device, for the treatment of an isolated IAA. In the present study, we have described the outcomes of the use of the Gore iliac branched endoprosthesis (IBE; W.L. Gore & Associates, Flagstaff, Ariz), without the support of an infrarenal endovascular aneurysm repair device, for the exclusion of an isolated IAA. The present study was an international multicenter retrospective cohort analysis. METHODS: All the patients who had undergone treatment with a solitary IBE for IAA exclusion from January 11, 2013 to December 31, 2018 were retrospectively reviewed. The primary outcome was technical success. The secondary outcomes included mortality, intraoperative and postoperative complications, and reintervention. RESULTS: A total of 18 European and American centers participated, with a total of 51 patients in whom 54 IAAs were excluded. The technical success rate was 94.1%, with an assisted technical success rate of 96.1%. No 30-day mortality occurred, with 98.1% patency of the internal and external iliac artery found at 24 months of follow-up. At 24 months of follow-up, 81.5% of the patients were free of complications and 90% were free of a secondary intervention. CONCLUSIONS: Treatment with a solitary IBE is a safe and, at midterm, an effective treatment strategy for selected patients with a solitary IAA.

Insect Immunity to Entomopathogenic Nematodes and Their Mutualistic Bacteria.

Entomopathogenic nematodes are important organisms for the biological control of insect pests and excellent models for dissecting the molecular basis of the insect immune response against both the nematode parasites and their mutualistic bacteria. Previous research involving the use of various insects has found distinct differences in the number and nature of immune mechanisms that are activated in response to entomopathogenic nematode parasites containing or lacking their associated bacteria. Recent studies using model insects have started to reveal the identity of certain molecules with potential anti-nematode or antibacterial activity as well as the molecular components that nematodes and their bacteria employ to evade or defeat the insect immune system. Identification and characterization of the genes that regulate the insect immune response to nematode-bacteria complexes will contribute significantly to the development of improved practices to control insects of agricultural and medical importance, and potentially nematode parasites that infect mammals, perhaps even humans.

Jump Squat is More Related to Sprinting and Jumping Abilities than Olympic Push Press.

The aim of this study was to test the relationships between jump squat (JS) and Olympic push press (OPP) power outputs and performance in sprint, squat jump (SJ), countermovement jump (CMJ) and change of direction (COD) speed tests in elite soccer players. 27 athletes performed a maximum power load test to determine their bar mean propulsive power (MPP) and bar mean propulsive velocity (MPV) in the JS and OPP exercises. Magnitude-based inference was used to compare the exercises. The MPV was almost certainly higher in the OPP than in the JS. The MPP relative to body mass (MPP REL) was possibly higher in the OPP. Only the JS MPP REL presented very large correlations with linear speed (r>0.7, for speed in 5, 10, 20 and 30 m) and vertical jumping abilities (r>0.8, for SJ and CMJ), and moderate correlation with COD speed (r=0.45). Although significant (except for COD), the associations between OPP outcomes and field-based measurements (speed, SJ and CMJ) were all moderate, ranging from 0.40 to 0.48. In a group composed of elite soccer players, the JS exercise is more associated with jumping and sprinting abilities than the OPP. Longitudinal studies are needed to confirm if these strong relationships imply superior training effects in favor of the JS exercise.

Treatment of Aortoiliac Occlusive Disease with the Endologix AFX Unibody Endograft.

OBJECTIVE/BACKGROUND: Aorto-bifemoral bypass remains the gold standard for treatment of aortoiliac occlusive disease (AIOD) in patients with advanced (TASC D) lesions, but has significant associated morbidity and mortality. Treatment with a unibody stent-graft positioned at the aortic bifurcation is a potential endovascular option for the treatment of AIOD. The current study examines the safety, efficacy, and early patency rates of the Endologix AFX unibody stent-graft for treatment of AIOD. METHODS: A multicenter retrospective review was conducted of patients treated exclusively for AIOD with the AFX device. Primary, assisted primary, and secondary patency rates were noted. Clinical improvement was assessed using Rutherford classification and ankle brachial index. Mean duration of follow-up was 22.2 ± 11.2 months. Ninety-one patients (56 males [62%]) were studied. RESULTS: Sixty-seven patients (74%) presented with lifestyle-limiting intermittent claudication and the remaining 24 (26%) had critical limb ischemia. Technical success was 100%. Complications included groin infection (n = 4 [4%]), groin hematoma (n = 4 [4%]), common iliac rupture (n = 4 [4%]), iliac dissection (n = 4 [4%]), and thromboembolic event (n = 3 [3%]; one femoral, one internal iliac artery, and one internal iliac with bilateral popliteal/tibial thromboemboli). Thirty-day mortality was 1% (1/91) resulting from a case of extensive pelvic thromboembolism. At 1 year, 73% of patients experienced improvement in Rutherford stage of -3 or greater compared with baseline. Nine patients (10%) required 16 secondary interventions. At all time points, primary patency rates were > 90%, assisted patency rates were > 98%, and secondary patency rates were 100%. CONCLUSION: This is the largest study to examine the use of the Endologix AFX unibody stent-graft for the treatment of AIOD. Use of the AFX stent-graft appears to be a safe and effective endovascular treatment for complex AIOD.

Ultrasound description of Pecs II (modified Pecs I): a novel approach to breast surgery.

OBJECTIVE: The Pecs block (pectoral nerves block) is an easy and reliable superficial block inspired by the infraclavicular block approach and the transversus abdominis plane blocks. Once the pectoralis muscles are located under the clavicle the space between the two muscles is dissected to reach the lateral pectoral and the medial pectoral nerves. The main indications are breast expanders and subpectoral prosthesis where the distension of these muscles is extremely painful. MATERIAL AND METHODS: A second version of the Pecs block is described, called "modified Pecs block" or Pecs block type II. This novel approach aims to block at least the pectoral nerves, the intercostobrachial, intercostals III-IV-V-VI and the long thoracic nerve. These nerves need to be blocked to provide complete analgesia during breast surgery, and it is an alternative or a rescue block if paravertebral blocks and thoracic epidurals failed. This block has been used in our unit in the past year for the Pecs I indications described, and in addition for, tumorectomies, wide excisions, and axillary clearances. RESULTS AND CONCLUSIONS: The ultrasound sequence to perform this block is shown, together with simple X-ray dye images and gadolinium MRI images to understand the spread and pathways that can explain the benefit of this novel approach.

Experience and technique for the endovascular management of iatrogenic subclavian artery injury.

BACKGROUND: Inadvertent subclavian artery catheterization during attempted central venous access is a well-known complication. Historically, these patients are managed with an open operative approach and repair under direct vision via an infraclavicular and/or supraclavicular incision. We describe our experience and technique for endovascular management of these injuries. METHODS: Twenty patients were identified with inadvertent iatrogenic subclavian artery cannulation. All cases were managed via an endovascular technique under local anesthesia. After correcting any coagulopathy, a 4-French glide catheter was percutaneously inserted into the ipsilateral brachial artery and placed in the proximal subclavian artery. Following an arteriogram and localization of the subclavian arterial insertion site, the subclavian catheter was removed and bimanual compression was performed on both sides of the clavicle around the puncture site for 20 min. A second angiogram was performed, and if there was any extravasation, pressure was held for an additional 20 min. If hemostasis was still not obtained, a stent graft was placed via the brachial access site to repair the arterial defect and control the bleeding. RESULTS: Two of the 20 patients required a stent graft for continued bleeding after compression. Both patients were well excluded after endovascular graft placement. Hemostasis was successfully obtained with bimanual compression over the puncture site in the remaining 18 patients. There were no resultant complications at either the subclavian or the brachial puncture site. CONCLUSION: This minimally invasive endovascular approach to iatrogenic subclavian artery injury is a safe alternative to blind removal with manual compression or direct open repair.

Multidimensional characterization of carotid artery stenosis using CT imaging: a comparison with ultrasound grading and peak flow measurement.

PURPOSE: Clinical decision making for carotid surgery depends largely upon stenosis grade. While digital subtraction angiography remains the gold standard for stenosis grading, many physicians use less invasive modalities. The purpose of this study was to compare the results of multidimensional Computed tomography (CTA) with ultrasound (US) grading and peak flow velocity (PSV). METHODS: 37 stenosed carotid arteries were studied retrospectively in 36 consecutive patients. US grading and PSV were compared to multidimensional CTA analysis (diameter, area and volumetric measurements), performed by a medical software company. Calculations of stenosis percentage on CTA were made using the NASCET and ECST methodology. Diameter measurements were also performed by a neuroradiologist. RESULTS: All CTA diameter, area and volume measurements had only modest correlation with PSV (r<0.5) and ultrasound grading (p<0.5). There was concordant classification of stenosis grades in only 40-60% of cases. CTA diameter, area and volume measurements had good correlation (0.69

An alloantibody to a high-prevalence MNS antigen in a person with a GP.JL/Mk phenotype.

The low-prevalence MNS blood group antigenTSEN is located at the junction of glycophorin A (GPA) to glycophorin B (GPB) in several hybrid glycophorin molecules. Extremely rare people have RBCs with a double dose of the TSEN antigen and have made an antibody to a high-prevalence MNS antigen. We report the first patient who is heterozygous for GYP.JL and Mk. During prenatal tests,an alloantibody to a high-prevalence antigen was detected in the serum of a 21-year-old Hispanic woman. The antibody detected an antigen resistant to treatment by papain, trypsin, alpha-chymotrypsin, or DTT. The antibody was strongly reactive by the IAT with all RBCs tested except those having the MkMk, GP.Hil/GP.Hil, or GP.JL/GP.JL phenotypes. The patient's RBCs typed M+N-S+/-s-U+, En(a+/-), Hut-, Mi(a-), Mur-, Vw-, Wr(a-b-), and were TSEN+, MINY+. Reactivity with Glycine soja suggested that her RBCs had a decreased level of sialic acid. Immunoblotting showed the presence of monomer and dimer forms of a GP(A-B) hybrid and an absence of GPA and GPB. Sequencing of DNA and PCR-RFLP using the restriction enzyme RsaI confirmed the presence of a hybrid GYP(AB). The patient's antibody was determined to be anti-EnaFR. She is the first person reported with the GP.JL phenotype associated with a deletion of GYPA and GYPB in trans to GYP.JL.

Expression and role of laminin-1 in mouse pancreatic organogenesis.

Previous studies have suggested that basement membrane alone may induce ductal differentiation and morphogenesis in the undifferentiated embryonic pancreas. The mechanism by which this induction occurs has not been investigated. Studies of other organ systems such as the lungs and mammary glands, where differentiation has been shown to be induced by basement membrane, have suggested a major role for laminin as a mediator of ductal or tubular morphogenesis and differentiation. We first defined the ontogeny of laminin-1 in the developing mouse pancreas. To determine the specific role of basement membrane laminin in pancreatic ductal morphogenesis and differentiation, we microdissected 11-day mouse embryonic pancreatic epithelium free from its surrounding mesenchyme and then suspended the explants in a 3-dimensional organ culture to allow us to assay cell differentiation and morphogenesis. When the pancreatic epithelium buds off the foregut endoderm, the pancreatic mesenchyme diffusely expresses laminin-1. This laminin subsequently organizes to the interface between the epithelium and the mesenchyme by E12.5. As gestation progresses, epithelial cells in direct contact with laminin-1 seem to differentiate into ducts and acini, whereas those spared intimate contact with laminin-1 appeared to organize into islets. Although basement membrane gel could induce pancreatic ductal morphogenesis of embryonic pancreatic epithelium, this induction was blocked when we added neutralizing antibodies against any of the following: 1) laminin (specifically laminin-1), 2) the "cross-region" of laminin-1, and 3) the alpha6 moiety of the integrin receptor, which is known to bind laminins. Immunohistochemistry, however, showed that pancreatic duct cell-specific differentiation (carbonic anhydrase II) without ductal morphogenesis was still present, despite the blockage of duct morphogenesis by the anti-laminin-1 neutralizing antibodies. Interestingly, there appeared to be a decrease in carbonic anhydrase II expression over time when the epithelia were grown in a collagen gel, rather than in a basement membrane gel. The pattern of laminin-1 expression in the embryonic pancreas supports the conclusion that laminin-1 is important in the induction of exocrine (ducts and acini) differentiation in the pancreas. Furthermore, our data demonstrate that 1) pancreatic ductal morphogenesis appears to require basement membrane laminin-1 and an alpha6-containing integrin receptor; 2) the cross-region of basement membrane laminin is a biologically active locus of the laminin molecule necessary for pancreatic ductal morphogenesis; 3) duct-specific cytodifferentiation, in the form of carbonic anhydrase II expression, is not necessarily coupled to duct morphogenesis; and 4) the basement membrane gel may contain components (e.g., growth factors) other than laminin-1 that can sustain both carbonic anhydrase II expression and, possibly, the capacity to form ducts, despite the absence of duct structures.

Mapping a social network of heterosexuals at high risk for HIV infection.

OBJECTIVE: To determine how heterosexuals at risk for HIV infection interconnect in social networks and how such relationships affect HIV transmission. DESIGN: Cross-sectional study with face-to-face interviews to ascertain sociosexual connections; serologic testing. PARTICIPANTS: Prostitute women (n = 133), their paying (n = 129) and non-paying (n = 47) male partners; injecting drug users (n = 200) and their sex partners (n = 41). Participants were recruited in sexually transmitted disease and methadone clinics, an HIV-testing site, and through street outreach in Colorado Springs, Colorado, USA. MAIN OUTCOME MEASURES: Reported behaviors, risk perceptions, sociosexual linkages, and HIV prevalence. RESULTS: Respondents were well informed, but reported engaging in high-risk behaviors frequently. Nevertheless, over 70% of respondents perceived themselves to be at low risk for HIV infection. The 595 respondents identified a social network of 5162 people to which they belonged. Network analytic methods indicated 147 separate connected components of this network; eight of the 19 HIV-positive individuals in the network were located in smaller components remote from the largest connected component. CONCLUSION: The isolated position of HIV-positive individuals may serve as a barrier to HIV transmission and may account for the lack of diffusion of HIV in heterosexual populations in this region. Network analysis appears useful for understanding the dynamics of disease transmission and warrants further development as a tool for intervention and control.

Pulse simulations of a mirrored counterpropagating-QPM device.

A basic mirrored counterpropagating quasi-phase-matched device is studied with a pulsed input fundamental plane wave using the method of lines and the relaxation method. Several examples are given under varying spatial pulse length to device length ratios. An approximate upper bound on the device length is established from this study for practical pulsed applications; the largest usable length is approximately the same as the spatial length of the pulse.

Distribution of beta-amyloid and amyloid precursor protein in the brain of spawning (senescent) salmon: a natural, brain-aging model.

Brain amyloid precursor protein (APP), a normal constituent of neurons, glial cells and cerebrospinal fluid, has several proposed functions (e.g., in neuronal growth and survival). It appears, however, that altered processing of APP is an initial or downstream step in the neuropathology of brain aging, Alzheimer's disease (AD), and Down's syndrome (DS). Some studies suggest that proteolytic cleavage of APP, producing beta-amyloid (Abeta(1-42)), could have neurotoxic or neuroprotective effects. In this study, we utilized antibodies to human APP(695) and Abeta(1-42,) and Congo red staining, to search for amyloid deposition in the brain of semelparous spawning kokanee salmon (Oncorhynchus nerka kennerlyi). Intracellular APP(695) immunoreactivity (APP-ir) was observed in brain regions involved in gustation (glomerulosus complex), olfaction (putative hippocampus, olfactory bulb), vision (optic tectum), the stress response (nucleus preopticus and nucleus lateralis tuberis), reproductive behavior (nucleus preopticus magnocellularis, nucleus preopticus periventricularis, ventral telencephalon), and coordination (cerebellum). Intra- and extra-neuronal Abeta(1-42) immunoreactivity (Abeta-ir) were present in all APP-ir regions except the nucleus lateralis tuberis and Purkinje cells of the cerebellum (coordination). Thus, the relationship between APP and Abeta deposition during brain aging could shed light on the processing of APP into Abeta, neurodegeneration, and possible protection of neurons that are functioning in spawning but senescent salmon. Pacific salmon, with their predictable and synchronized life history, could provide research options not available with the existing models for studies of brain aging and amyloidosis.

Basement membrane exposure defines a critical window of competence for pancreatic duct differentiation from undifferentiated pancreatic precursor cells.

We previously showed that the undifferentiated pancreatic epithelium can differentiate into islets, ducts, or acini depending on its milieu and that laminin is necessary for pancreatic duct formation. Therefore we wanted to study the plasticity of laminin-induced duct differentiation the better to understand mechanisms of pancreatic duct lineage selection induced by basement membrane. Mouse embryonic pancreases were dissected at gestational day 11 (E11.5), and epithelium was isolated from its surrounding mesenchyme. Some epithelia were cultured in a collagen gel devoid of laminin. These epithelia were "rescued" at days 1-7 of culture by transferring them to a laminin-rich matrix (Matrigel) for 7 additional days. Other epithelia were instead first cultured in Matrigel, and then placed into collagen. Immunohistochemistry was performed for insulin, amylase, and carbonic anhydrase II. Pancreatic epithelia rescued from collagen into laminin during days 1-4 after harvest were still able to form ducts, whereas epithelia deprived of laminin for longer than this 4-day window were not. Pancreatic epithelia exposed to laminin for as little as 1 day, and then placed into collagen, still retained the ability to make ducts. Thus there is a clear cut-off in the development of the pancreatic epithelium at E11.5, after which laminin appears necessary to induce duct formation. We believe that such "windows of competence" in embryonic development imply that developmental programs in the embryo allow some flexibility.

Ontogeny of activin B and follistatin in developing embryonic mouse pancreas: implications for lineage selection.

Activin, a member of the transforming growth factor-beta superfamily, has been shown to be a critical regulator in exocrine and endocrine pancreas formation. The purpose of our study was to describe the ontogeny of activin B and its inhibitor, follistatin, in developing pancreas and to elucidate potential mechanisms for exocrine and endocrine lineage selection. Mouse embryonic pancreata were dissected at various ages (day 10 [E10.5] to birth [E18.5]), sectioned, and immunostained for activin B (one of two existing isomers, A and B), follistatin, insulin, and glucagon. In addition, reverse transcriptase-polymerase chain reaction was employed to determine the messenger RNA expression of follistatin in isolated pancreatic epithelia and mesenchyme of various ages. Activin B was first detected at E12.5 in epithelial cells coexpressing glucagon. At E16.5 these coexpressors appeared as clusters in close proximity to early ducts. By E18.5 activin B was localized to forming islets where cells coexpressed glucagon and were arranged in the mantle formation characteristic of mature alpha cells. Follistatin was found to be ubiquitous in pancreatic mesenchyme at early ages by immunohistochemical analysis, disappearing sometime after E12.5. Follistatin reappeared in E18.5 islets and remains expressed in adult islets. Follistatin messenger RNA was first detected in epithelium at E11.5, preceding its protein expression in islets later in gestation. We propose that mesenchyme-derived follistatin inhibits epithelium-derived activin at early embryonic ages allowing for unopposed exocrine differentiation and relative suppression of endocrine differentiation. At later ages the decrease in the amount of mesenchyme relative to epithelium and the subsequent drop in follistatin levels liberates epithelial activin to allow differentiation of endocrine cells to form mature islets by the time of birth.

Successful limb reperfusion using prolonged intravascular shunting in a case of an unstable trauma patient--a case report.

When peripheral vascular injuries present in conjunction with life threatening emergencies, controlling hemorrhage from a peripheral blood vessel may take initial priority, however, sacrificing a limb to preserve life is a well-established dictum. The use of intravascular shunts has allowed arterial and venous injuries to be controlled and temporized while treating other injuries. Typically, intravascular shunts are used for short time periods while orthopedic injuries are repaired or other life threatening injuries are managed. The following case demonstrates the long-term use of an intravascular arterial shunt to treat a traumatic transection of the common femoral artery and vein in a patient with an open pelvic fracture from blunt trauma. A 20-year-old woman fell between a subway platform and an oncoming train. She sustained a crush injury to her lower extremity and pelvis as she was pinned between the train and platform. The patient presented with active hemorrhage from a groin laceration, quickly became hemodynamically unstable, and was brought to the operating room. In addition to a pelvic fracture with massive pelvic hematoma she sustained a complete transection of the bifurcation of the common femoral artery (CFA), the common femoral vein (CFV), and associated orthopedic injuries. Vascular shunts were placed in the common femoral artery and vein. The patient became hypotensive from an expanding retroperitoneal hematoma. Pelvic bleeding was controlled with angioembolization and the venous injury was repaired. At this time the patient became cold, acidotic, and coagulopathic. It was thought unsafe to proceed with the arterial repair and it was elected to keep her arterial shunts in place and perform a planned reexploration in 24 hours after correcting her physiologic status. The patient returned to the operating room for an elective repair of her CFA the following day. Her shunt had remained patent throughout this time. She underwent a reverse saphenous vein graft from her CFA to her SFA. After a prolonged hospital course she was ultimately transferred to a rehabilitation center with intact pulses in both lower extremities. This case demonstrates the effectiveness of prolonged (>6 hours) use of an intravascular shunt as part of damage control surgery for peripheral arterial and venous injuries. In a patient who would otherwise undergo an amputation for their injury, the risk of shunt thrombosis, or infection, during damage control resuscitation may not be a contraindication for placement.

An in vitro mouse model of cleft palate: defining a critical intershelf distance necessary for palatal clefting.

It is unclear whether cleft palate formation is attributable to intrinsic biomolecular defects in the embryonic elevating palatal shelves or to an inability of the shelves to overcome a mechanical obstruction (such as the tongue in Pierre Robin sequence) to normal fusion. Regardless of the specific mechanism, presumably embryonic palatal shelves are ultimately unable to bridge a critical distance and remain unapproximated, resulting in a clefting defect at birth. We propose to use a palate organ culture system to determine the critical distance beyond which embryonic palatal shelves fail to fuse (i.e., the minimal critical intershelf distance). In doing so, we hope to establish an in vitro cleft palate model that could then be used to investigate the contributions of various signaling pathways to cleft formation and to study novel in utero treatment strategies. Palatal shelves from CD-1 mouse embryos were microdissected on day 13.5 of gestation (E13.5; term = 19.5 days), before fusion. Using a standardized microscope ocular grid, paired palatal shelves were placed on a filter insert at precisely graded distances ranging from 0 (in contact) to 1.9 mm (0, 0.095, 0.19, 0.26, 0.38, 0.48, 0.57, 0.76, 0.95, and 1.9 mm). A total of 68 paired palatal shelves were placed in serum-free organ culture for 96 hours (n = 68). Sample sizes of 10 were used for each intershelf distance up to and including 0.48 mm (n = 60). For intershelf distances of 0.57 mm and greater, two-paired palatal shelves were cultured (n = 8). All specimens were assessed grossly and histologically for palatal fusion. Palatal fusion occurred in our model only when intershelf distances were 0.38 mm or less. At 0.38 mm, eight of 10 palates appeared grossly adherent, whereas six of 10 demonstrated clear fusion histologically with resolution of the medial epithelial seam and continuity of the palatal mesenchyme. None of the 18 palates fused when placed at intershelf distances of 0.48 mm or greater. Using our selected intershelf distances as a guideline, we have established an approximate minimal critical intershelf distance (0.48 mm) at which we can reliably expect no palatal fusion. Culturing palatal shelves at intershelf distances of 0.48 mm or greater results in nonfusion or clefting in vitro. This model will allow us to study biomolecular characteristics of unfused or cleft palatal shelves in comparison with fused shelves. Furthermore, we plan to study the efficacy of grafting with exogenous embryonic mesenchyme or candidate factors to overcome clefting in vitro as a first step toward future in utero treatment strategies.

Immunolocalization of fibroblast growth factor receptors 1 and 2 in mouse palate development.

Recent evidence has implicated mutations of fibroblast growth factor receptors (FGF-R) in the pathogenesis of craniosynostotic syndromes. Cleft palate can be a component of such syndromes. The expression of FGF-R1 and FGF-R2 has been delineated in normally developing cranium, where they seem to regulate cellular differentiation and proliferation, respectively. The specific role of fibroblast growth factor signaling in mammalian palate development is unclear. The authors investigated the patterns of expression of FGF-R1 and FGF-R2 throughout mouse palatal development in the embryo. Time-dated CD-1 mouse heads (n = 135) were harvested at embryonic ages 12.5, 13.5, 14.5, 15.5, and 16.5 days (term gestation = 19.5 days), fixed in paraformaldehyde, embedded in paraffin, and sectioned. In addition, paired palatal shelves (n = 30) were isolated by means of microdissection from embryonic day--13.5 embryos, grown on Millipore filters in serum-free medium in vitro for 24, 48, 72, or 96 hours and processed for histological analysis. Immunohistochemical analysis for FGF-R1 and FGF-R2 was performed on the in vivo and in vitro specimens. FGF-R1 and FGF-R2 were found to be specifically expressed in the epithelium of the developing palatal shelves from the time of their outgrowth from the maxillary processes through completion of fusion in vivo and in vitro. Expression of both receptors was particularly strong during the phases of medial epithelial-medial epithelial contact between the individual shelves, through the formation of the medial epithelial seam, to the ultimate dissolution of the seam. Such a pattern of expression seems to implicate fibroblast growth factor signaling in the regulation of the critical phase of fusion of the bilateral shelves. The expression of both FGF-R1 and FGF-R2 in the lateral palatal mesenchyme, where such secondary structures as tooth primordia and bone begin to appear, also suggests a role for fibroblast growth factor signaling in the induction of ongoing differentiation and maturation of the palate after fusion. These data suggest that fibroblast growth factor signaling may play a role in the epithelial-mesenchymal interactions that dictate fusion and maturation of the developing palate. Furthermore, the data are consistent with the correlation of cleft palate formation with aberrant fibroblast growth factor signaling.

Defective fibroblast growth factor signaling allows for nonbranching growth of the respiratory-derived fistula tract in esophageal atresia with tracheoesophageal fistula.

BACKGROUND/PURPOSE: The fistula tract in esophageal atresia with tracheoesophageal fistula (EA-TEF) appears to arise from a trifurcation of the embryonic lung bud. Subsequently, it does not branch like the other bronchi, which also arise from the lung bud. Previous results have implied that aberrant mesenchymal-epithelial signaling in the developing foregut, possibly involving fibroblast growth factors, may allow for the nonbranching growth of the fistula, and the ultimate development of the fistula tract in TEF. METHODS: Adriamycin injections into pregnant rat dams induced EA-TEF formation in rat embryos. Control and Adriamycin-exposed embryos were harvested on the 13th gestational day, and the developing foregut was isolated with microdissection. mRNA was isolated from the developing fistula tract, embryonic lung, and normal embryonic esophagus. Reverse transcription-polymerase chain reaction (RT-PCR) for the IIIb splice variant of the FGF2R receptor was performed. Foregut specimens also were processed for histologic analysis, and immunofluorescence for FGF1 was performed. RESULTS: FGF2R-IIIb is specifically absent from the developing fistula tract in TEF, whereas it is present in the normal developing lung and esophagus. FGF1 also is uniquely absent from the developing fistula tract, but it is present in the normal lung mesenchyme. CONCLUSIONS: FGF1, FGF7, and FGF10 are critical mesenchymal factors that mediate proliferation and branching morphogenesis by the developing respiratory epithelium. The absence of FGF2R-IIIb, the obligate common receptor for FGF7 and FGF10, from the fistula tract, and the absence of FGF1 in the fistula tract mesenchyme, collectively imply the absence of a specific FGF signaling pathway in the developing fistula tract. This absence of FGF signaling could explain the lack of branching by the developing fistula tract as it grows caudally in the abnormally developing embryo. Downregulation of these components of the FGF signaling pathways may allow for a patterned compensation by the embryo for the proximal foregut atresia in this anomaly. This compensation may then reestablish gastrointestinal continuity as the fistula tract connects to the developing stomach.

Retinoid signaling directs secondary lineage selection in pancreatic organogenesis.

BACKGROUND/PURPOSE: Retinoid signaling plays an important role in many differentiation pathways. Retinoid signaling has been implicated in the induction of differentiation by pancreatic ductal cancer cell lines and in patients with pancreatic cancer. The authors wished to better understand the role of retinoid signaling in pancreatic development. METHODS: Embryonic pancreas was harvested from mice at serial gestational ages and immunohistochemical analysis was performed for retinoic acid receptors (RAR-alpha, RAR-beta, RAR-gamma), and retinoid X receptors (RXR-alpha, RXR-beta, and RXR-gamma). Also, early embryonic pancreases were cultured for 7 days with exogenous 9-cis retinoic acid (9cRA) or all-trans retinoic acid (atRA) and analyzed histologically and immunohistochemically. RESULTS: Retinoid receptors were expressed in a lineage-specific distribution, with stronger expression for many in the exocrine compartment. The receptors were not often expressed until late gestation. Exogenous 9cRA induced predominantly ducts instead of acini, plus more mature endocrine (islet) architecture. Exogenous atRA induced predominantly acini instead of ducts, with no apparent endocrine effect. CONCLUSIONS: Retinoids may have an important role in pancreatic differentiation, with a particular effect on secondary lineage selection between ductal and acinar phenotype. Because the control of ductal versus acinar differentiation has been implicated strongly in the pathogenesis of pancreatic ductal carcinoma, these results may lay the groundwork for studies in the mechanism of induced differentiation of pancreatic ductal cancer by retinoids.

Left subclavian artery coverage during TEVAR: is revascularization necessary?

Thoracic endovascular aortic repair (TEVAR) has rapidly become a viable and accepted treatment option for atherosclerotic aortic aneurysms as well as a variety of other aortic pathologies including ulcers, dissection, coarctation and disruption. Left subclavian artery (LSA) coverage is often necessary to achieve proximal seal in up to 40% of patients treated with TEVAR. The management of the LSA in this cohort of patients remains controversial. Studies in support of routine pre-operative LSA revascularization show that coverage of the LSA during TEVAR is associated with an increased risk of stroke, paraplegia and arm ischemia. Other studies show that intentional coverage of the LSA without revascularization is not associated with increased morbidity and lends support to those who advocate more selective LSA revascularization during TEVAR (i.e. in those patients with patent LIMA-coronary bypass, dominant or isolated left vertebral artery, or a functioning left upper extremity (LUE) dialysis arteriovenous fistula). This paper is intended to review the literature comparing routine and selective LSA revascularization after TEVAR to determine the best management strategy.