Ectopic thyroid gland in the porta hepatis and lingua.

A rare case of an ectopic thyroid gland in the porta hepatis and in the tongue in an asymptomatic euthyroid 24-year-old woman is reported. A solitary inhomogeneous, hypoechogenic and hyperechogenic mass in the porta hepatis was accidentally discovered by ultrasonography. Subsequent computed tomography demonstrated a heterogeneous, well-defined tumor with small calcifications without signs of environmental invasion. A hemangioma and focal nodular hyperplasia were excluded by blood pool and hepatobiliary scintigraphy. Surprisingly, fine-needle aspiration cytology revealed normal thyroid tissue. (123)I-scintigraphy confirmed the presence of ectopic dual thyroid tissue in the hepatic porta and lingua. At clinical inspection the lingual thyroid gland was palpable and visible, and appeared solid and spheroidal. The subhepatic, ectopic thyroid mass was resected. Postoperatively, thyroid hormone replacement was started to prevent an enlargement of the lingual thyroid. Today, 4 years after surgery, the patient remains euthyroid.     

A very rare vascular complication of the Edwards expandable eSheath during transcatheter aortic valve replacement

Transcatheter aortic valve replacement (TAVR) has revolutionized the management of severe symptomatic aortic valve stenosis. TAVR is now indicated as an alternative to surgical replacement in a wide risk profile ranging from high to low surgical risk. Although vascular complications have decreased in frequency over time, with the introduction of lower profile delivery systems and sheaths, they remain one of the most frequently encountered and serious complications of TAVR. Patient-specific predisposing factors have been well characterized. However, much less is known about device-specific complications. Awareness of the possible device-related complications may lead to earlier identification, prompt management, and better outcomes. We report a previously unreported complication of the Edwards expandable eSheath that lead to avulsion of the external iliac artery following successful TAVR with a 29-mm Edwards Sapien 3 transcatheter heart valve. Bleeding was promptly controlled with an occlusion balloon and emergency surgical repair was required with a favorable outcome.     

The relationship between ascending aortic diameter with left atrial functions and left ventricular mass index in a population with normal left ventricular systolic function

Aim

Ascending aortic dilatation is a common clinical issue. In the present study, we aimed to evaluate the relationship between ascending aortic diameter with left ventricular (LV) and left atrial (LA) functions, and LV mass index (LVMI) in a population with normal LV systolic function.

Methods

A total of 127 healthy participants with normal LV systolic function took part in the study. Echocardiographic measurements were obtained from each subject.

Results

The mean age of the participants was 43 ± 14.1 years and 76 (59.8%) were female. The mean aortic diameter of the participants was 32.2 ± 4.7 mm. A negative correlation was found between aortic diameter and LV systolic function (LVEF r = -.516, p < .001; Gls r = -.370). In addition, there was a strong positive correlation between aortic diameter with LV wall thicknesses, LVMI (r = .745, p < .001), and systolic and diastolic diameters. The relationship between aortic diameter and diastolic parameters was evaluated, a negative correlation with Mitral E, Em, E/A ratio, and a positive correlation with MPI, Mitral A, Am, E/Em ratio were found.

Conclusion

A strong correlation between ascending aortic diameter with LV and LA functions, and LVMI in individuals with normal LV systolic function.     

Circulating markers of endothelial and alveolar epithelial dysfunction are associated with mortality in pediatric acute respiratory distress syndrome

Purpose

Angiopoietin 2 (Ang2) and soluble receptor for advanced glycation end products (sRAGE) are markers of endothelial and pulmonary epithelial damage with prognostic implications in adult acute respiratory distress syndrome (ARDS), but unclear significance in pediatric ARDS (PARDS).

Methods

This was a prospective, observational study in children with PARDS (2012 Berlin and 2015 PALICC definitions) at the Children’s Hospital of Philadelphia. Plasma was collected within 48 h of PARDS onset and biomarkers quantified by enzyme-linked immunosorbent assay.

Results

In 82 children with PARDS (12 deaths, 15 %), Ang2 and sRAGE were higher in non-survivors than survivors (p < 0.01 for both). Mortality was highest in patients with Ang2 and sRAGE levels both above median values. Ang2 and sRAGE correlated with the number of non-pulmonary organ failures (both p < 0.001). Ang2 was higher in indirect lung injury and in immunocompromised children. In stratified analysis, both Ang2 and sRAGE were associated with mortality only in direct lung injury and in immunocompetent children, with no association evident in indirect lung injury or in immunocompromised children.

Conclusions

Ang2 and sRAGE in early PARDS were higher in non-survivors than survivors and strongly correlated with number of non-pulmonary organ failures. When stratified by type of lung injury, Ang2 and sRAGE were associated with mortality only in direct lung injury. Similarly, when stratified by immunocompromised status, Ang2 and sRAGE were associated with mortality only in immunocompetent children. The utility of these biomarkers for prognostication and risk stratification requires investigation.

     

Minireview: structural and functional evolution of the thyrotropin receptor

TSH receptor (TSHR) is a member of the leucine-rich repeat-containing G protein-coupled receptors. Both TSHR and its ligand TSH have evolved to acquire specificity, minimize cross-reaction to other glycoprotein hormone receptors, and modulate cognate interaction (and thereby thyrotropic activity). TSHR sequences available from two life orders, teleost and mammals, were analyzed. Teleost TSHRs with low affinity are expressed in many nonthyroidal tissues and show a tendency to gene duplication. In some teleosts, TSHR has limited specificity, and in others extremely high constitutive activity, suggesting the possibility of ligand-independent receptor function. Although mammalian TSHR, in contrast to other glycoprotein hormone receptors, maintains relatively high constitutive activity, the thyrotropic activity of TSH appears to decline in hominoids including humans, probably as part of metabolic adaptation to the changing environment. Critical TSHR residues that determine hormone specificity have been identified in the leucine-rich repeats, and others within the cysteine-rich C-flanking region that determines hormonal activation as well as receptor silencing. Transmembrane (TM) helices, particularly the TM5 and TM6, are likely involved in receptor homodimerization and a unique motif in TM7 appears essential to receptor silencing and internalization. Surprisingly, ternary structures in the intracellular domain as opposed to specific sequence motifs are critical for intracellular TSHR trafficking. It is evident that progress in understanding structure-function relationships of TSHR and its ligand can be further stimulated by inclusion of evolutionary analysis of their primary, secondary and tertiary structure. Such an integrated approach should also contribute to the rational design of highly efficacious therapeutics with either agonistic or antagonistic properties.     

A new silent germline mutation of the TSH receptor: coexpression in a hyperthyroid family member with a second activating somatic mutation.

BACKGROUND: Up to date, three thyroid-stimulating hormone receptor (TSHR) germline variants have been reported for which no functional consequences have been detected by in vitro characterizations. However, familial nonautoimmune hyperthyroidism and hot nodules are clearly associated with constitutively activating TSHR germline mutations. We describe a family with a new TSHR germline mutation that is associated with euthyroidism in 13 family members and hyperthyroidism in 1 family member. METHODS: Mutation analysis of the TSHR gene was performed by denaturing gradient gel electrophoresis. TSHR constructs were characterized by determination of cell surface expression, 3'-5'-cyclic adenosine monophosphate (cAMP) accumulation, and constitutive cAMP activity. RESULTS: A novel TSHR germline mutation (N372T) was found in a man who presented with thyrotoxicosis. The mutation was also detected in 13 family members, all of whom were euthyroid. Interestingly, an additional constitutively active somatic mutation (S281N) was identified on the second parental TSHR allele of the hyperthyroid index patient. Linear regression analysis showed a lack of constitutive activity for N372T. Moreover, coexpression studies of N372T with S281N did not reveal any evidence for a functional influence of N372T on the constitutively active mutation (CAM). CONCLUSIONS: N372T is unlikely to cause altered thyroid function. This is consistent with the finding that only the index patient with the additional somatic mutation S281N was hyperthyroid.     

Small Bowel Polyposis Syndromes

Intestinal polyposis syndromes are relatively rare. However, it is important for clinicians to recognize the potential risks of these syndromes. Based on histology, these syndromes can be classified mainly into hamartomatous polyposis syndromes and familial adenomatous polyposis (FAP), which affects mainly the large intestine. This review discusses the clinical manifestations and underlying genetics of the most common small intestinal polyposis syndromes: Peutz-Jeghers syndrome (PJS), juvenile polyposis (JP), PTEN hamartoma tumor syndrome (PHTS), and the small intestinal implications of familial adenomatous polyposis (FAP).     

Presence and diagnosis of amebic infestation in Turkish patients with active ulcerative colitis

BackgroundIt is difficult to definitively diagnose acute amebiasis, particularly when this condition is superimposed on inflammatory bowel disease. Our goals in this study were to determine the prevalence of amebiasis in individuals with active ulcerative colitis, and to identify clinical and laboratory parameters that are of value for diagnosing amebiasis in this patient group.MethodsThe subjects were 111 patients (76 women, 35 men) with confirmed active ulcerative colitis who attended our hospital's Inflammatory Bowel Disease Outpatient Clinic between May 2002 and March 2006. In each case, a detailed medical history was collected, blood samples were tested for inflammatory markers, and stool samples were evaluated for presence of amebae using an Enzyme-Linked Immunosorbent Assay (ELISA) for detection of Entamoeba histolytica antigen. The clinical and laboratory variables for the ELISA-positive and ELISA-negative groups were compared.ResultsAmebiasis was detected in 35 (31.5%) of the subjects. Patient age, disease duration, endoscopic activity index, serum C-reactive protein level, and white blood cell count were not useful for diagnosing amebiasis in this patient group.ConclusionsGiven the high rate of amebiasis observed in our patients with active ulcerative colitis, we recommend that, in Turkey any individual with ulcerative colitis who presents with symptoms of disease activation should be tested for ameba using antigen detection kits. A high index of suspicion is especially important in any region where E. histolytica is endemic.     

Inferior Vena Cava-Tricuspid Annulus Isthmus is a Critical Site of Unidirectional Block During the Induction of Common Atrial Flutter

Background: Until recently no clinical studies had reported precise right atrium (RA) mapping when performing induction of atrial flutter (AFI). We studied the mode of tachycardia initiation in 16 patients (pts) referred for radiofrequency (RF) AFl ablation. AFl induction was performed at the beginning of the procedure (n &equals; 10), or after previous AFl termination during RF delivery (n &equals; 6). Detailed analysis of AFl initiation was provided by duodecapolar (Halo) and multipolar catheters positioned in the peritricuspidian region at the lateral right atrial wall (LRA), the inferior vena cavatricuspid annulus (IVC-TA) isthmus and the interatrial septum. Induction was obtained during incremental pacing (IAP) (15 pts) or programmed stimulation (1 pt) from the proximal coronary sinus (PCS).Results: Atrial flutter with counterclockwise (CCW) RA rotation was induced in all pts by PCS pacing. During PCS IAP, at long pacing cycle lengths, impulse propagated in a clockwise (CW) direction through the IVC-TA isthmus and then upward at low (L) LRA. This led to a collision at the mid LRA with another wave front propagating in a CCW direction at the septum. IAP from PCS induced a progressive delay of propagation at the IVC-TA isthmus resulting in a prolongation of the PCS-Mid Isthmus interval from 85&plusmn;29 to 151&plusmn;42 msec. At same pacing cycle lengths (CL), the PCS-HLRA interval was comparatively less prolonged, from 75&plusmn;12 to 105&plusmn;18 msec, p &equals; 0.0007. This preferential slowing of conduction between PCS and mid isthmus, during IAP from PCS, was associated with a displacement of the zone of collision to the Low LRA. Finally a CW functional block occurred at the IVC-TA isthmus and CCW AFl was induced through a period of transient concealed entrainment. The paced CL required to initiate flutter ranged from 290 to 180 msec and the mean CL of induced atrial flutter was 254&plusmn;27 msec.Conclusions: The IVC-TA isthmus has decremental properties and exhibits wenckebach phenomenon during incremental PCS pacing. Initiation of a counterclockwise flutter by PCS pacing is associated with appearance of a functional unidirectional block at the IVC-TA isthmus.     

Rare β-Globin Gene Mutations in Pakistan

The aim of this study was to analyze the rare β-thalassemia (β-thal) mutations in the Pakistani population. A total of 8716 unrelated Pakistani individuals having children with transfusion-dependent thalassemia were investigated by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for the previously reported common and rare β-thal mutations. Genomic sequencing of the β-globin gene and its immediate 5' and 3' flanking regions was done where no known mutation was found. Out of the 8716 individuals studied, 88 (1.0%) were not characterized by ARMS-PCR. Genomic sequencing revealed that 67 (0.82%) individuals had 19 different β-thal mutations including one novel mutation (HBB: c.136delT). The remaining 21 (0.26%) individuals did not show any mutation on the β-globin gene and its immediate flanking regions. The characterized alleles included seven (0.09%) in the 5' untranslated region (5'UTR), 29 (0.35%) in the coding regions, and 31 (0.38%) in the splice junction regions. HBB: c.92+1G>A and HBB: c.113G>A were the most frequently seen rare mutations. The spectrum of β-thal mutations in the Pakistani population is very diverse. In addition to the already reported mutations, another 19 different types of mutations were found. Interestingly, 21 individuals who had children with transfusion-dependent thalassemia and one known β-thal mutation, did not show any mutation on the β-globin gene. HBB: c.92+1G>A and HBB: c.113G>A are the most frequently seen rare mutations in Pakistan.