A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.     

Detection of Leishmania donovani and L. tropica in Ethiopian wild rodents

Human visceral (VL, also known as Kala-azar) and cutaneous (CL) leishmaniasis are important infectious diseases affecting countries in East Africa that remain endemic in several regions of Ethiopia. The transmission and epidemiology of the disease is complicated due to the complex life cycle of the parasites and the involvement of various Leishmania spp., sand fly vectors, and reservoir animals besides human hosts. Particularly in East Africa, the role of animals as reservoirs for human VL remains unclear. Isolation of Leishmania donovani parasites from naturally infected rodents has been reported in several endemic countries; however, the status of rodents as reservoirs in Ethiopia remains unclear. Here, we demonstrated natural Leishmania infections in rodents. Animals were trapped in 41 localities of endemic and non-endemic areas in eight geographical regions of Ethiopia and DNA was isolated from spleens of 586 rodents belonging to 21 genera and 38 species. Leishmania infection was evaluated by real-time PCR of kinetoplast (k)DNA and confirmed by sequencing of the PCR products. Subsequently, parasite species identification was confirmed by PCR and DNA sequencing of the 18S ribosomal RNA internal transcribed spacer one (ITS1) gene. Out of fifty (8.2%) rodent specimens positive for Leishmania kDNA-PCR and sequencing, 10 were subsequently identified by sequencing of the ITS1 showing that five belonged to the L. donovani complex and five to L. tropica. Forty nine kDNA-positive rodents were found in the endemic localities of southern and eastern Ethiopia while only one was identified from northwestern Ethiopia. Moreover, all the ten ITS1-positive rodents were captured in areas where human leishmaniasis cases have been reported and potential sand fly vectors occur. Our findings suggest the eco-epidemiological importance of rodents in these foci of leishmaniasis and indicate that rodents are likely to play a role in the transmission of leishmaniasis in Ethiopia, possibly as reservoir hosts.     

Laterally spreading tumors--experience based on 138 consecutive cases

BACKGROUND/AIMS: Laterally spreading tumors (LST) are flat elevated neoplastic lesions with diameters equal to or greater than 10 mm. The treatment results of 138 lesions in 131 patients are presented here as a part of a retrospective analysis. METHODOLOGY: Two gastroenterology centers participated in the study in the period from 1/2002-12/2006. During colonoscopy, each superficial lesion was classified according to the Paris endoscopic classification. Endoscopic mucosal resection (EMR) lift and cut was employed. Treatment was considered successful when both endoscopic and histo-pathological criteria of complete resection were fulfilled. RESULTS: A total of 138 LST in 131 patients were diagnosed. Average LST diameter was 25 mm. A total of 5 (3.6%) lesions in 4 patients were referred for primary surgery. One patient was treated with argon plasma coagulation only. EMR was attempted for 132/138 (95.7%) of all LST and was successful in 125 (90.6%) cases. Complications occured in 16/132 (12.1%) patients. Severe complications, defined as decession, emergency surgery, emergency endoscopy and transfusion of eryhrocyte concentrate occured in 5/132 (3.8%). One (0.7%) 69 year-old-male patient died on the third day following EMR due to complications of acute myocardial infarction. CONCLUSION: LST lesions could be efficiently treated with EMR lift and cut method with a reasonable rate of complications.     

Protective anti-V antibodies inhibit Pseudomonas and Yersinia translocon assembly within host membranes

Pathogenic Yersinia species and Pseudomonas aeruginosa share a similar type III secretion/translocation system. The translocation system consists of 3 secreted proteins, YopB/PopB, YopD/PopD, and LcrV/PcrV; the latter is known to be a protective antigen. In an in vitro assay, the translocation system causes the lysis of erythrocytes infected with wild-type (wt) P. aeruginosa. wt Y. enterocolitica is not hemolytic, but a multiknockout mutant deprived of all the effectors and of YopN ( Delta HOPEMN) is hemolytic. In the presence of antibodies against PcrV and Y. pestis LcrV, the hemolytic activity of P. aeruginosa was inhibited. Similarly, the hemolytic activity of Delta HOPEMN was inhibited in the presence of anti-LcrV antibodies. The assembly of the translocon, composed of PopB/D and YopB/D proteins, was disturbed in immunoprotected erythrocyte membranes, mimicking the phenotypes of V knockout mutants. Thus, protective antibodies against the V antigens of Yersinia species and P. aeruginosa act at the level of the formation of the translocon pore in membranes of infected host cells by blocking the function of LcrV/PcrV. The hemolysis assay could be adapted for high-throughput screening of anti-infectious compounds that specifically target the type III translocon.     

Symptoms of advanced heart failure—A case for radiofrequency catheter ablation?

A sixty-year-old man with previous history of coronary artery disease was admitted due to progressive worsening of dyspnoea at exertion (NYHA III functional class) and no angina. Coronary angiography confirmed occlusion of the right coronary artery which was naturally bypassed by homocollaterals with TIMI 3 flow to the peripheral branches. The lesion was not technically suitable for percutaneous angioplasty. The left coronary artery was without stenosis. On echocardiography, both the left ventricle and the left atrium were dilated and hemodynamically significant mitral regurgitation was present. Surface ECG showed a left bundle branch block with repeated runs of monomorphic ventricular ectopic beats (PVC). Radiofrequency catheter ablation of the focus in the posteroseptal region of the left ventricle underneath the mitral valve was performed using electroanatomical mapping system. After the procedure, mitral regurgitation decreased and reverse remodeling of the left ventricle and the left atrium occurred with concomitant significant clinical improvement of the patient. The authors discuss several treatment strategies: mitral valve repair surgery combined with revascularization, implantation of a biventricular ICD system or elimination of the focus of monomorphic VT runs by radiofrequency catheter ablation as a possible causal approach in the treatment of PVC-induced cardiomyopathy.