Rare case of divided phrenic nerve variation: a cadaveric case report.

The phrenic nerve innervates the respiratory diaphragm, the primary muscle active during ventilation. The canonical path of the phrenic nerve originates from the cervical spine at C3-C5 spinal nerves and travels inferiorly through the neck and thoracic cavity to reach the diaphragm. During a cadaver dissection, a variation of the phrenic nerve was discovered in a 93-year-old male specimen. A traditional origin of the phrenic nerve was noted; however, the nerve branched into medial and lateral components at the level of the superior trunk of the brachial plexus. The branches reconnected at the apex of the aortic arch and continued inferiorly to innervate the ipsilateral diaphragm. This case study describes a rare type of branching of the phrenic nerve and explores its potential impact on clinical procedures.

Association between nutritional risk status and both diaphragmatic dysfunction and diaphragm atrophy in medical intensive care unit patients / Asociación entre el estado de riesgo nutricional y la disfunción diafragmática y la atrofi a del diafragma en pacientes de la unidad de cuidados intensivos médicos

Aim: critical illness often leads to malnutrition and diaphragmatic dysfunction (DD), common in intensive care units (ICU). Ultrasonography (US) is a potent tool for detecting DD. This study examines the connection between malnutrition risk and DD in ICU patients using ultrasonographic diaphragm measurements in medical ICU patients. Methods: we assessed nutritional risk using risk screening tools and mid-upper arm circumference measurements (MUAC). Diaphragm atrophy (DA) and DD were evaluated by measuring diaphragmatic excursion (DE), thickness, and thickening fraction (TF) by US. We then compared these diaphragmatic measurements in patients based on their nutritional risk scores. Results: of the fifty patients studied, 54 % to 78 % were at risk of malnutrition, 28 % exhibited diaphragm atrophy (DA), and 24 % showed DD upon ICU admission. Malnutrition risk diagnosed by all nutritional risk screening tools was significantly more frequent in patients with DD, while diagnosed by MUAC was considerably higher in patients with DA. A total of 16 patients (32 %) died during their ICU stay, with DD, DA, and malnutrition risks (as identified by the mNUTRIC Score) being more prevalent among non-survivors (p < 0.05). Malnutrition risk (as determined by the mNUTRIC Score) was an independent risk factor for DD [OR (95 % CI): 6.6 (1.3-34), p = 0.03]. Conclusion: malnutrition risk may be significantly associated with DD and DA in medical ICU patients upon ICU admission.(AU)

Objetivo: las enfermedades graves a menudo conducen a desnutrición y disfunción diafragmática (DD), comunes en las unidades de cuidados intensivos (UCI). La ultrasonografía (US) es una herramienta poderosa para detectar la DD. Este estudio examina la conexión entre riesgo de desnutrición y DD en pacientes de UCI utilizando mediciones ultrasonográficas del diafragma.Métodos: evaluamos el riesgo nutricional utilizando herramientas de evaluación de riesgos y mediciones de la circunferencia del brazo en su punto medio superior (MUAC). La atrofia del diafragma (DA) y la DD se evaluaron midiendo la excursión diafragmática (DE), el grosor y la fracción de engrosamiento (TF) por ecografía. Luego, comparamos estas mediciones diafragmáticas en pacientes según sus puntuaciones de riesgo nutricional. Resultados: de los cincuenta pacientes estudiados, entre el 54 % y el 78 % estaban en riesgo de desnutrición, el 28 % presentaban atrofia del diafragma (DA) y el 24 % mostraban DD al ingreso en la UCI. El riesgo de desnutrición diagnosticado por todas las herramientas de evaluación del riesgo nutricional fue significativamente más frecuente en los pacientes con DD, mientras que el diagnosticado por el MUAC fue considerablemente mayor en los pacientes con DA. Un total de 16 pacientes (32 %) fallecieron durante su estancia en la UCI, siendo la DD, la DA y los riesgos de desnutrición (según lo identificado por la puntuación mNUTRIC) más prevalentes entre los no sobrevivientes (p < 0,05). El riesgo de desnutrición (según lo determinado por la puntuación mNUTRIC) fue un factor de riesgo independiente de la DD [OR (95 % CI): 6,6 (1,3-34), p = 0,03]. Conclusión: en este estudio se encontró una asociación significativa entre el riesgo de desnutrición y la disfunción diafragmática, así como con la atrofia diafragmática al ingreso en la UCI.(AU)

Congenital Diaphragmatic Hernia - Diagnosis After Intra-Thoracic Cholecystitis.

Congenital diaphragmatic hernia due to diaphragmatic agenesis is extremely rare. We report the case of a 53-year-old female patient with a congenital right diaphragmatic hernia due to a right hemidiaphragm agenesia diagnosed in the context of acute intrathoracic cholecystitis. She was admitted to the Emergency Department for diffuse abdominal pain, nausea and vomiting with 2 days of evolution. Thoracic and abdominal radiography showed hydro-aerial levels in the right hemithorax. The computed tomography showed a right diaphragmatic hernia with signs of incipient incarceration. The patient underwent surgery consisting of a right exploratory thoracotomy, reduction of the hernial contents, closure of the defect with a double-sided prosthesis anchored in a pericardial patch, and pericardial reconstruction with a polypropylene prosthesis, with a remarkable evolution. This case shows a rare late presentation of a congenital hemidiaphragm agenesia in adulthood, with a special focus on the indications and surgical techniques used for its correction.

The role of genes and environment in the etiology of congenital diaphragmatic hernias.

Structural birth defects are a common cause of abnormalities in newborns. While there are cases of structural birth defects arising due to monogenic defects or environmental exposures, many birth defects are likely caused by a complex interaction between genes and the environment. A structural birth defect with complex etiology is congenital diaphragmatic hernias (CDH), a common and often lethal disruption in diaphragm development. Mutations in more than 150 genes have been implicated in CDH pathogenesis. Although there is generally less evidence for a role for environmental factors in the etiology of CDH, deficiencies in maternal vitamin A and its derivative embryonic retinoic acid are strongly associated with CDH. However, the incomplete penetrance of CDH-implicated genes and environmental factors such as vitamin A deficiency suggest that interactions between genes and environment may be necessary to cause CDH. In this review, we examine the genetic and environmental factors implicated in diaphragm and CDH development. In addition, we evaluate the potential for gene-environment interactions in CDH etiology, focusing on the potential interactions between the CDH-implicated gene, Gata4, and maternal vitamin A deficiency.

Embryology and anatomy of congenital diaphragmatic hernia.

Prenatal and postnatal treatment modalities for congenital diaphragmatic hernia (CDH) continue to improve, however patients still face high rates of morbidity and mortality caused by severe underlying persistent pulmonary hypertension and pulmonary hypoplasia. Though the majority of CDH cases are idiopathic, it is believed that CDH is a polygenic developmental defect caused by interactions between candidate genes, as well as environmental and epigenetic factors. However, the origin and pathogenesis of these developmental insults are poorly understood. Further, connections between disrupted lung development and the failure of diaphragmatic closure during embryogenesis have not been fully elucidated. Though several animal models have been useful in identifying candidate genes and disrupted signalling pathways, more studies are required to understand the pathogenesis and to develop effective preventative care. In this article, we summarize the most recent litterature on disrupted embryological lung and diaphragmatic development associated with CDH.

Confiabilidad interevaluador de la medición de la excursión diafragmática y fracción de engrosamiento diafragmático mediante ultrasonografía en voluntarios sanos / Inter-rater reliability of the measurement of diaphragmatic excursion and fraction of diaphragmatic thickening by ultrasonography in healthy volunteers

Antecedentes y objetivo: Determinar la confiabilidad interevaluador en la medición ultrasonográfica (US) de la excursión diafragmática (ED) y la fracción de engrosamiento diafragmático (FED) realizada por profesionales de salud no médicos en voluntarios sanos. Participantes y métodos: Estudio observacional prospectivo en un hospital de tercer nivel en Cali, Colombia. Se realizaron mediciones a 30 voluntarios sanos escogidos mediante muestreo a conveniencia, sin antecedentes de enfermedades pulmonares, con edades entre los 18-60 años. Previamente se realizó una prueba piloto con 8 voluntarios sanos. Las mediciones US de ED y FED se basaron en protocolos publicados anteriormente. Cada evaluador observaba independientemente varios ciclos de respiración tranquila normal durante 3minutos para establecer una línea de base. Para evaluar la confiabilidad interevaluador en las mediciones de ED y FED se utilizó el índice de correlación intraclase (ICC), con intervalos de confianza del 95% y un p<0,05. Resultados: Se identificó concordancia sustancial en la medición de la ED en las ventanas esplénica y hepática debido a que el ICC fue mayor a 0,6 (p<0,05). La medición de la FED en la ventana hepática mostró concordancia leve tanto en el modo 2D como en el modo M (p>0,05). En la ventana esplénica la medición de la FED en el modo 2D se identificó concordancia regular y para el modo M se encontró una concordancia leve (p>0,05). Conclusiones: La US diafragmática constituye un método reproducible con aceptable confiabilidad interevaluador para la medición del grosor inspiratorio/espiratorio y con confiabilidad pobre para la medición de FED.(AU)

Background and objective: To determine the inter-rater reliability in the ultrasonographic (US) measurement of the diaphragmatic excursion (DE) and the diaphragm thickness fraction (DTF) performed by non-medical health professionals in healthy people. Participants and methods: Prospective observational study in a third level hospital in Cali, Colombia. Measurements were made to 30 healthy volunteers chosen by convenience sampling, without a history of lung diseases, with ages between 18-60 years. A pilot test was previously carried out with 8 healthy volunteers. US measurements of DE, and DTF were based on previously published protocols. Each assessor independently observed several cycles of normal quiet breathing for 3minutes to establish a baseline. The Intraclass Correlation Index (ICC) was used to evaluate the inter-rater reliability in the measurements of DE and DTF, with 95% confidence intervals and a P<.05. Results: Substantial agreement was identified in the measurement of DE in the splenic and hepatic windows because the ICC was greater than 0.6 (P<.05). The measurement of the DTF in the hepatic window showed slight agreement in both 2D and M modes (P>.05). In the splenic window, the measurement of the DTF in the 2D mode was found to be moderate agreement and for the M mode a slight agreement was found (P>.05).Conclusions: The diaphragmatic US constitutes a reproducible method with acceptable inter-rater reliability for the measurement of inspiratory/expiratory thickness, and with little reliability for the measurement of DTF.(AU)

Parvovirus B19 Intrauterine Infection and Eventration of the Diaphragm.

Parvovirus B19 infection in pregnancy may have a poor outcome for the fetus. Ocular anomalies, brain damage with hydrocephalus and central nervous system (CNS) scarring, cleft lip and hypospadias, as well myocarditis and congenital heart disease have been reported. We present a case of a preterm female neonate born with ascites, hydrothorax and congenital diaphragmatic eventration (CDE), with a prenatal diagnosis of congenital diaphragmatic hernia (CDH). The neonate was born prematurely at 32 weeks gestation with caesarean section due to a previous caesarean delivery. She was immediately intubated in the delivery room, transferred in the Neonatal Intensive Care Unit (NICU) and supported with high frequency oscillatory ventilation (HFOV). The diagnosis of CDH was sonographically estimated from the 20th week of gestation and surgical correction was decided. During surgery CDE was diagnosed instead of CDH and despite postoperatively care the neonate developed disseminated intravascular coagulation and finally died in the 40th hour of life. Along with the identification of parvovirus B19 in the pleural fluid by PCR, the biopsy of the diaphragm revealed connective tissue, full of vasculature and absence muscle tissue. Although only cytomegalovirus, rubella, and toxoplasmosis were considered to be associated with CDE, parvovirus B19 might also be related to this congenital diaphragmatic malformation. In CDE, the function of the lungs can be compromised as a consequence of the compression applied by the abdominal organs. The neonatologists should include this condition in their differential diagnosis for a more direct and effective management.

Surgical management of diaphragmatic and thoracic endometriosis': A French multicentric descriptive study.

INTRODUCTION: Surgical management of Diaphragmatic and thoracic endometriosis (DTE) is still controversial, a thoracic or an abdominal approach can be proposed. METHODS: We conducted a multicentric retrospective study in 8 thoracic, gynecology or digestive surgery units in 5 French university hospitals. The main objective was to review the current management of DTE. RESULTS: 50 patients operated for DTE from 2010 to 2017 were included: 26 with a thoracic approach and 24 with an abdominal approach. Preoperative pelvic endometriosis (PE) concerned 25 patients. In 38 patients, DTE diagnosis was made on clinical symptoms (pneumothorax (n = 19), chronic or catamenial chest pain (n = 18) or hemopneumothorax (n = 1)). Median time from onset of symptoms to diagnosis was 47 months (0-212). PE surgery concurrently occurred in 22 patients. We report diaphragmatic nodules, pleuropulmonary nodules and diaphragmatic perforations in 42, 5 and 22 women respectively. Lesions were right-sided in 45 patients. Nodules were destructed in 12 cases and resected in 38 cases. When a diaphragmatic reconstruction was needed (n = 31), a simple suture was performed in 26 patients, while 5 patients needed a mesh repair. Pleural symphysis was performed for all patients who received a thoracic approach. DTE resection was considered complete in 46 patients. Three patients had severe 30-days complications of DTE surgery. Median follow-up was 20 months (range 1-69). Recurrence occurred in 10 patients. CONCLUSION: The results emphasize the importance of systematically looking for chest pain in patients suffering from PE and underline the lack of a standardized procedure and treatment in DTE.

Shrinking lung syndrome in pediatric systemic lupus erythematosus.

OBJECTIVE: To describe clinical, radiological and treatment characteristics in pediatric patients with SLS. MATERIAL AND METHODS: This is a descriptive and retrospective study in patients under 16 years old with the diagnosis of SLE complicated by SLS at the General Hospital. National Medical Center La Raza. Clinical, radiological and treatment variables were analyzed. Results are shown in frequencies and percentages. RESULTS: Data from 11 patients, 9 females and 2 males were collected. Mean age at diagnosis of SLS was 12.2 years. Age at diagnosis of SLE was 11.1 years. SLEDAI 17.3. Renal desease 72%, hematological 91%, lymphopenia 63%, mucocutaneous 72%, neurological 9%, arthritis 54%, serositis 91%, fever 81%, secondary antiphospholipid syndrome, low C3 72%, low C4 81%, positive ANA 91%, positive anti-DNA 91%. Regarding clinical manifestations of SLE: cough 81%, dyspnea 91%, hipoxemia 81%, pleuritic pain 71%, average oxygen saturation 83%. Chest X-rays findings: right hemidiaphragm affection 18%, left 63%, bilateral 18%. Elevated hemidiaphragm 91%, atelectasis 18%, pleural effusion 91%, over one third of the cardiac silhouette under the diphragm 36%, bulging diaphragm 45%, 5th. anterior rib that crosses over the diaphragm 91%. M-mode ultrasound: diaphragmatic hypomotility 100%, pleural effusion 63%. Pulmonary function tests: restrictive pattern in 45% of the cases. Treatment was with supplementary oxygen 100%, intubation 18%, antibiotics 100%, steroids 100%, intravenous immunoglobulin 54%, plasmapheresis 18%, cyclophosphamide 54% and rituximab 18%. The clinical course was favorable in 81%. CONCLUSIONS: SLS should be suspected in patients with SLE and active disease who present hipoxemia, pleuritic pain, cough, dyspnea, pleural effusion and signs of restriction on chest X-rays. Therefore, a diaphragmatic M-mode ultrasound should be performed in order to establish the diagnosis.

Laparoscopic patch repair of a Morgagni hernia in Menkes disease.

The association between Morgagni hernia and Menkes disease has not yet been described. Here, we report such a rare association in an 8-year-old boy who presented with subocclusive symptoms. He successfully underwent laparoscopic repair with a patch. The patch was fixed to the anterior abdominal wall by using transfascial sutures with extracorporeal knot tying and to the remaining edges of the diaphragmatic defect by using intracorporeal suturing and spiral tacks. At the 2-year follow-up, the child remained recurrence-free and without gastrointestinal symptoms. The potential relationship between the two conditions and the controversial use of spiral tacks to affix the mesh to the diaphragm are also discussed.

Ultrasound shear wave elastography for assessing diaphragm function in mechanically ventilated patients: a breath-by-breath analysis.

BACKGROUND: Diaphragm dysfunction is highly prevalent in mechanically ventilated patients. Recent work showed that changes in diaphragm shear modulus (ΔSMdi) assessed using ultrasound shear wave elastography (SWE) are strongly related to changes in Pdi (ΔPdi) in healthy subjects. The aims of this study were to investigate the relationship between ΔSMdi and ΔPdi in mechanically ventilated patients, and whether ΔSMdi is responsive to change in respiratory load when varying the ventilator settings. METHODS: A prospective, monocentric study was conducted in a 15-bed ICU. Patients were included if they met the readiness-to-wean criteria. Pdi was continuously monitored using a double-balloon feeding catheter orally introduced. The zone of apposition of the right hemidiaphragm was imaged using a linear transducer (SL10-2, Aixplorer, Supersonic Imagine, France). Ultrasound recordings were performed under various pressure support settings and during a spontaneous breathing trial (SBT). A breath-by-breath analysis was performed, allowing the direct comparison between ΔPdi and ΔSMdi. Pearson's correlation coefficients (r) were used to investigate within-individual relationships between variables, and repeated measure correlations (R) were used for determining overall relationships between variables. Linear mixed models were used to compare breathing indices across the conditions of ventilation. RESULTS: Thirty patients were included and 930 respiratory cycles were analyzed. Twenty-five were considered for the analysis. A significant correlation was found between ΔPdi and ΔSMdi (R = 0.45, 95% CIs [0.35 0.54], p < 0.001). Individual correlation displays a significant correlation in 8 patients out of 25 (r = 0.55-0.86, all p < 0.05, versus r = - 0.43-0.52, all p > 0.06). Changing the condition of ventilation similarly affected ΔPdi and ΔSMdi. Patients in which ΔPdi-ΔSMdi correlation was non-significant had a faster respiratory rate as compared to that of patient with a significant ΔPdi-ΔSMdi relationship (median (Q1-Q3), 25 (18-33) vs. 21 (15-26) breaths.min-1, respectively). CONCLUSIONS: We demonstrate that ultrasound SWE may be a promising surrogate to Pdi in mechanically ventilated patients. Respiratory rate appears to negatively impact SMdi measurement. Technological developments are needed to generalize this method in tachypneic patients. TRIAL REGISTRATION: NCT03832231 .

Diaphragmatic excursion measurement in emergency department patients with acute dyspnea to predict mechanical ventilation use.

INTRODUCTION: Ultrasound is a feasible and reproducible method for measuring right diaphragmatic excursion (RDE) in ED patients with acute dyspnea (AD). In AD patients, the correlation between the RDE value and the need for mechanical ventilation (MV) is not known. MATERIALS: This was a bicentric, observational prospective study. The RDE measurement was done at admission. The need for MV was defined by the use of MV within 4 h of AD management. An optimal threshold for RDE was determined as the value that minimized the incorrect predictions of the use of MV in the first 4 h as the highest Youden index. RESULTS: We analyzed 102 patients (79 [70; 86] years), 38 (37%) of whom had been ventilated. The RDE value was 1.7 cm [1.4; 2.0] and 2.2 cm [1.8; 2.6] in the ventilated and non-ventilated groups, respectively (p = 0.06). The AUC was 0.68 95% CI [0.57; 0.80]. With a threshold of 2 cm, the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 76% [60%; 89%], 59% [46%; 71%], 81% [67%; 91%], and 53% [39%; 66%], respectively. In the non-COPD patients, the RDE values were 1.5 cm [1.2; 1.9] and 2.2 cm [1.8; 2.6] (p < 0.01) in the ventilated and not-ventilated groups, respectively. The AUC was 0.77 95% CI [0.64; 0.90]. With a threshold of 2.18 cm, the sensitivity, specificity, NPV, and PPV were 91% [71%; 99%], 51% [36%; 66%], 92% [75%; 99%], and 54% [38%; 69%], respectively. CONCLUSION: The RDE values at ED admission were unable to define a prognostic threshold value associated with subsequent MV need in the AD patients. In non-COPD patients, the NPV was 92%.

Surgical treatment of 125 cases of congenital diaphragmatic eventration in a single institution.

BACKGROUND: This study sought to investigate the clinical characteristics of congenital diaphragmatic eventration (CDE) and to compare the efficacies of thoracoscopy and traditional open surgery in infants with CDE. METHODS: We retrospectively analyzed the clinical data of 125 children with CDE (90 boys, 35 girls; median age: 12.2 months, range: 1 h-7 years; body weight: 1.99-28.5 kg, median body weight: 7.87 ± 4.40 kg) admitted to our hospital in the previous 10 years, and we statistically analyzed their clinical manifestations and surgical methods. RESULTS: A total of 108 children in this group underwent surgery, of whom 67 underwent open surgery and 41 underwent thoracoscopic diaphragmatic plication. A total of 107 patients recovered well postoperatively, except for 1 patient who died due to respiratory distress after surgery. After 1-9.5 years of follow-up, 107 patients had significantly improved preoperative symptoms. During follow-up, the location of the diaphragm was normal, and no paradoxical movement was observed. Eleven of the 17 children who did not undergo surgical treatment did not have a decrease in diaphragm position after 1-6 years of follow-up. The index data on the operation time, intraoperative blood loss, chest drainage time, postoperative mechanical ventilation time, postoperative hospital stay and postoperative CCU admission time were better in the thoracoscopy group than in the open group. The difference between the two groups was statistically significant (P < 0.05). CONCLUSIONS: The clinical symptoms of congenital diaphragmatic eventration vary in severity. Patients with severe symptoms should undergo surgery. Both thoracoscopic diaphragmatic plication and traditional open surgery can effectively treat congenital diaphragmatic eventration, but compared with open surgery, thoracoscopic diaphragmatic plication has the advantages of a short operation time, less trauma, and a rapid recovery. Thus, thoracoscopic diaphragmatic plication should be the first choice for children with congenital diaphragmatic eventration.

Capnothorax During Laparoscopy in Trendelenburg Position: A Rare Case Study.

Pneumothorax is an infrequent complication of laparoscopic surgery. Most cases occur during upper abdominal surgery, since a head-down position (Trendelenburg) pushes the liver and peritoneum against the diaphragm, reducing gas release. When it is due to CO2 diffusion across congenital diaphragmatic defects, it usually resolves itself spontaneously after de-insufflation of the pneumoperitoneum. Increasing positive end-expiratory pressure to counteract intra-abdominal pressure is an effective measure when a pulmonary origin is excluded. We report a case of right-sided hypertensive capnothorax due to a diaphragmatic defect, during lower abdominal surgery, which was successfully managed without the need for chest drainage. This case highlights the importance of maintaining active vigilance and a high index of suspicion for pneumothorax during laparoscopic surgery.

O pneumotórax é uma complicação pouco frequente da cirurgia laparoscópica. A maioria dos casos ocorrem em cirurgias da região abdominal superior, uma vez que a posição de Trendelenburg por empurrar o fígado e o peritoneu contra o diafragma, reduz a perda de gás. Quando a causa é a difusão de CO2 através de um defeito diafragmático congénito, habitualmente resolve espontaneamente, após a desinsuflação do pneumoperitoneu. Quando se exclui uma causa parenquimatosa pulmonar o aumento de positive end-expiratory pressure para contrabalançar a pressão intra-abdominal é uma medida eficaz. O caso clínico que apresentamos refere-se a um caso de capnotórax hipertensivo que ocorreu devido à presença de um defeito diafragmático congénito, durante uma cirurgia abdominal inferior e que foi tratado com sucesso sem recorrer ao uso de dreno torácico. Este caso salienta a importância de manter uma vigilância ativa e alto indice de suspeição para o pneumotórax durante a cirurgia laparoscópica.

Dissociation between reduced diaphragm inspiratory motion and normal diaphragm thickening in acute chronic pulmonary obstructive disease exacerbation: a case report.

INTRODUCTION: Patients with chronic pulmonary obstructive disease (COPD) are at risk of acute exacerbation. Diaphragm muscle is classically highly solicited in COPD exacerbation. PATIENT CONCERNS: A COPD patient was admitted because of acute dyspnea with wheezing. DIAGNOSIS: acute COPD exacerbation. INTERVENTIONS: A diaphragm ultrasound and a Doppler echocardiography were performed at bedside. OUTCOMES: We measured diaphragm thickening at the apposition zone and diaphragm inspiratory motion from the subcostal view, in addition with classical echocardiographic parameters. CONCLUSION: Despite a normal diaphragm thickening, diaphragm motion during inspiration is reduced in acute COPD exacerbation. These apparently discrepant findings may be explained by the alterations of the respiratory mechanics during COPD exacerbations, which should be considered when evaluating the diaphragmatic function by imaging.

Functional domains of the FgfrL1 receptor.

FgfrL1 is a novel growth factor receptor that is primarily expressed in musculoskeletal tissues and the kidney. FgfrL1-deficient mice have a malformed diaphragm and no kidneys. Such animals die immediately after birth because they are not able to inflate their lungs. The FgfrL1 molecule is composed of three extracellular Ig domains, a transmembrane helix and a short intracellular domain. To investigate the contribution of each of these domains to the function of the novel receptor, we generated mice with deletions of the individual domains. Mice lacking the intracellular domain are viable and phenotypically normal. Mice lacking the first (N-terminal) Ig domain are also viable and normal, but have a reduced life span. Mice lacking the Ig2 or the Ig3 domain are born alive, but die within 24 â€‹h after birth. Ig2-deficient animals exhibit substantially smaller kidneys than wild-type littermates and contain a lower number of glomeruli. Ig3-deficient mice completely lack metanephric kidneys. Interestingly, both the Ig2 and the Ig3-deficient animals show only minor alterations in the diaphragm, which still enables them to inflate their lungs after birth. Our results demonstrate that the principal function of the FgfrL1 receptor is to control the growth of the metanephric kidneys by regulating nephrogenesis. It appears that this function is primarily accomplished by the Ig3 domain with some contribution of the Ig2 domain. It is conceivable that the two domains interact with an Fgf ligand and another molecule from the surface of neighboring cells to induce condensation of the metanephric mesenchyme to renal epithelia and glomeruli.

Roles of Collagen XXV and Its Putative Receptors PTPσ/δ in Intramuscular Motor Innervation and Congenital Cranial Dysinnervation Disorder.

Intramuscular motor innervation is an essential process in neuromuscular development. Recently, mutations in COL25A1, encoding CLAC-P/collagen XXV, have been linked to the development of a congenital cranial dysinnervation disorder (CCDD). Yet the molecular mechanisms of intramuscular innervation and the etiology of CCDD related to COL25A1 have remained elusive. Here, we report that muscle-derived collagen XXV is indispensable for intramuscular innervation. In developing skeletal muscles, Col25a1 expression is tightly regulated by muscle excitation. In vitro and cell-based assays reveal a direct interaction between collagen XXV and receptor protein tyrosine phosphatases (PTPs) σ and δ. Motor explant assays show that expression of collagen XXV in target cells attracts motor axons, but this is inhibited by exogenous PTPσ/δ. CCDD mutations attenuate motor axon attraction by reducing collagen XXV-PTPσ/δ interaction. Overall, our study identifies PTPσ/δ as putative receptors for collagen XXV, implicating collagen XXV and PTPσ/δ in intramuscular innervation and a developmental ocular motor disorder.

Massive hiatus hernia associated with scoliosis in a female cadaver

Kyphoscoliosis is often associated with enlarged oesophageal hiatus. It is suggested that this spinal deformity leads to prolonged stretching of the diaphragm causing herniation of abdominal organs, particularly the stomach into the thorax. Such a hiatal hernia can compress thoracic viscera, produce symptoms like shortness of breath and intermittent pain after ingestion of food. This cadaveric report discusses a case of a giant, sliding-type of hiatal hernia accompanied by scoliosis with rightsided deviation of the thoracic aorta and smallsized left lung. All patients presenting gastrointestinal symptoms with coexistence of vertebral column anomalies should be evaluated for the occurrence of intra-thoracic stomach

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