Membrane vesicles shed by Legionella pneumophila inhibit fusion of phagosomes with lysosomes

When cultured in broth to the transmissive phase, Legionella pneumophila infects macrophages by inhibiting phagosome maturation, whereas replicative-phase cells are transported to the lysosomes. Here we report that the ability of L. pneumophila to inhibit phagosome-lysosome fusion correlated with developmentally regulated modifications of the pathogen's surface, as judged by its lipopolysaccharide profile and by its binding to a sialic acid-specific lectin and to the hydrocarbon hexadecane. Likewise, the composition of membrane vesicles shed by L. pneumophila was developmentally regulated, based on binding to the lectin and to the lipopolysaccharide-specific monoclonal antibody 3/1. Membrane vesicles were sufficient to inhibit phagosome-lysosome fusion by a mechanism independent of type IV secretion, since only approximately 25% of beads suspended with or coated by vesicles from transmissive phase wild type or dotA secretion mutants colocalized with lysosomal probes, whereas approximately 75% of beads were lysosomal when untreated or presented with vesicles from the L. pneumophila letA regulatory mutant or E. coli. As observed previously for L. pneumophila infection of mouse macrophages, vesicles inhibited phagosome-lysosome fusion only temporarily; by 10 h after treatment with vesicles, macrophages delivered approximately 72% of ingested beads to lysosomes. Accordingly, in the context of the epidemiology of the pneumonia Legionnaires' disease and virulence mechanisms of Leishmania and Mycobacteria, we discuss a model here in which L. pneumophila developmentally regulates its surface composition and releases vesicles into phagosomes that inhibit their fusion with lysosomes.     

Hemodynamical assessment of cavernous hemangioma in cavernous sinus using MR-DSA and conventional DSA

We report a hemodynamical assessment of the blood turnover pattern as well as the imaging of cavernous hemangioma in a cavernous sinus using time-resolved contrast enhanced 2D projection MRA, also known as MR-DSA, and conventional digital subtraction angiography (DSA), before and after radiotherapy. MR-DSA showed very fast dynamical images of a contrast turnover pattern and was well matched with the findings obtained from DSA. MR-DSA is a non-invasive study, and can replace DSA in examining a vascular tumor for the initial work-up and follow-up examination.     

Long term follow up of through-the-scope balloon dilation as compared to strictureplasty and bowel resection of intestinal strictures in crohn’s disease

Background & aims: Ileo-colonic strictures are common complication of Crohn’s disease (CD), and may result in repeated endoscopic or surgical therapy with a risk of further complications, such as perforation or short bowel syndrome. Strictures develop as a consequence of tissue remodelling and fibrosis due to chronic inflammation. This study compares the outcome of CD patients undergoing primarily endoscopic treatment with those undergoing surgery at an university hospital. Methods: In this study we retrospectively included 88 CD patients with intestinal strictures (37 males, 51 females, mean age 40 years, range 19-65 years) of both our medical and our surgical department, who underwent either surgical or endoscopic therapy between January 2002 and January 2006 with prospective, controlled follow-up, extended till January 2010 (mean follow-up period: 5 years; range 4-8 years). The primary end-point was operation- and symptom-free time. Patients were primarily divided into four groups: only surgical therapy, only endoscopic therapy, endoscopy with subsequent surgery, and initial surgical therapy followed by endoscopic dilations. Results: 53% of all patients remained surgery-free with mean follow-up of 49 months; a single endoscopic dilation was sufficient enough in 9 patients to achieve a surgery-free time of 51 months, other patients required up to 5 dilations. The average interval between first and second dilation was 6.5 months, between second and third 10.5 months. In the group of patients with only endoscopic therapy, surgery- and symptom-free time was shorter, as compared to the group of only surgical therapy. We found that stenoses in the surgical group with an average length of 6.5 cm were as expected longer, as compared to the endoscopic group (3 cm, ranging from 2-4 cm). The surgery-free time was 49 months (42-71 months, P = 0.723) with a symptom-free time of 12 months (4.5-46 months, P = 0.921). In the group of only surgically treated patients, 68.4% of the patients had only one stenosis, 18.4% had 2-3 stenoses and 13.2% more than 3 stenoses. In all patients the surgery- and symptoms- free time was 69 months (57-83 months, P = 0.850 and 0.908). The other two groups showed similar results. We found no significant effect of characteristic of stenosis (length, inflammation, the number of stenoses), injection of prednisolone, disease activity at the time of dilation and medication at the time of dilation on the long-term outcome. Importantly, the success of symptom free time correlated with the diameter of the balloon. Conclusions: Endoscopic dilation should be considered as a first-line therapy for short, accessible, fibrotic strictures. Careful patient selection and proper diagnostic imaging pre-procedure are essential requirements for safe and successful treatment. The balloon diameter seems to correlate positively with the long term outcome of dilation. However, at ever shorter intervals between endoscopic interventions, surgery should be discussed as an option for further treatment.     

Characterization of a newly emerged genetic cluster of H1N1 and H1N2 swine influenza virus in the United States

H1 influenza A viruses that were distinct from the classical swine H1 lineage were identified in pigs in Canada in 2003–2004; antigenic and genetic characterization identified the hemagglutinin (HA) as human H1 lineage. The viruses identified in Canadian pigs were human lineage in entirety or double (human–swine) reassortants. Here, we report the whole genome sequence analysis of four human-like H1 viruses isolated from U.S. swine in 2005 and 2007. All four isolates were characterized as triple reassortants with an internal gene constellation similar to contemporary U.S. swine influenza virus (SIV), with HA and neuraminidase (NA) most similar to human influenza virus lineages. A 2007 human-like H1N1 was evaluated in a pathogenesis and transmission model and compared to a 2004 reassortant H1N1 SIV isolate with swine lineage HA and NA. The 2007 isolate induced disease typical of influenza virus and was transmitted to contact pigs; however, the kinetics and magnitude differed from the 2004 H1N1 SIV. This study indicates that the human-like H1 SIV can efficiently replicate and transmit in the swine host and now co-circulates with contemporary SIVs as a distinct genetic cluster of H1 SIV.     

Malunion of the clavicle causes significant glenoid malposition: a quantitative anatomic investigation

Objective An experimental cadaver model was used to assess the effects of a malunited fracture of the middle third of the clavicle on the functional anatomy of the shoulder joint.Method Anatomic samples were prepared with simulated shortening and axial malposition of the clavicle. From these, alterations in glenoid fossa position were measured and depicted graphically.Results Healing of clavicle fractures with bony shortening leads to a ventromedialcaudal shift in glenoid fossa position. The following malpositions of the clavicle lead to the respective glenoid fossa positional changes: caudal deviation leads to a mediocaudal shift, cranial deviation leads to a dorsolateral shift of the glenoid fossa, ventral deviation causes a ventrolateral shift, dorsal deviation leads to mediocaudal shift of the fossa, cranial rotation leads to ventrolateral shift in fossa position, and caudal rotation leads to a dorsomedial shift in glenoid fossa position.Conclusion Clinical implication of these data is that bony shortening in combination with caudal displacement leads to distinct functional deficits in abduction, particularly overhead motion. Using the above data, a vector model was created to calculate position of the glenoid fossa dependent on clavicle position/malposition. The model is a valuable tool to be used for planning open reduction and fixation of clavicular fractures or malunions.     

Delayed diagnosis of adrenal hypoplasia congenita in a patient with a new mutation in the NR0B1 gene

Determining the precise cause of adrenal insufficiency occurring in infancy is of critical importance for both the correct management of affected children and the provision of correct genetic advice to their families. We report a case of a 24-year-old, male patient bearing a new mutation in the DAX1 gene. The patient was born at term, from a healthy pregnancy. Adrenal insufficiency was diagnosed in the fourth week of life with a salt-wasting syndrome, but it was mistakenly believed to be secondary to congenital adrenal hyperplasia (CAH). On hydrocortisone substitution, the child continued to develop normally, but the diagnosis of CAH was questioned, which led to an episode of an abrupt withdrawal of hydrocortisone substitution and subsequently caused a reoccurrence of a life-threatening salt-wasting syndrome. Owing to close follow-up, the patient's gonadal axis deficiency was promptly identified, which allowed an assisted but successful onset of puberty. We proposed the diagnosis of adrenal hypoplasia congenita (AHC) in this patient and identified a hemizygous mutation (c.1130delAinsGT, p.E377GfsX12) in exon 1 of the NR0B1 gene. To our knowledge, the detected mutation has not been described previously (HGMD Professional 2010.4, Human Gene Mutation Database, Biobase, Beverly, MA, USA). It leads to a frameshift, a premature stop codon, and, most likely, non-sense-mediated decay of the mutant mRNA. In this case, close patient follow-up minimized the detrimental consequences of an incorrect diagnosis. Nevertheless, it highlights the importance of the early precise diagnosis of patients with AHC.     

Mechanical circulatory support for patients with peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) challenges different disciplines including gynecologists, cardiologists and cardiac surgeons. It is a severe cardiac failure occurring at the end of pregnancy or within the first months after delivery. Urgent intervention is necessary to stabilize hemodynamics with appropriate medication and mechanical assist support. Data of 4 patients with PPCM at a mean age of 28.2 years were analyzed retrospectively. Echocardiography was used to evaluate cardiac function. Despite varying courses of PPCM all women received left ventricular assist devices (LVAD) since their hemodynamics could not be stabilized by medical treatment. Mean gestational week at delivery was 31.5 ± 4.9. Left ventricular ejection fractions of all patients were severely impaired (17.8 ± 3.5 %) before LVAD implantations. After long-term mechanical support (282 and 417 days, respectively) 2 patients were successfully transplanted. Two other females could be weaned from LVAD therapy after 944 and 612 days, respectively. LVAD explanations were performed according to a standardized weaning protocol. Myocardial recovery was confirmed by regular echocardiography, spiroergometry and right heart catheterization. Mechanical assist device support is a surgical strategy either as bridge to transplantation or as bridge to recovery for patients with PPCM.     

Attachment representations in 6-year-olds: related longitudinally to the quality of attachment in infancy and mothers' attachment representations

A new method to assess attachment representations in children by applying a story completion procedure in doll play (SCPDP) is presented. Transmission and continuity of attachment were tested in 28 German families by using the Strange Situation procedure (SS) with the mother and her infant, the Adult Attachment Interview (AAI) with the mother when the child is 5 years old, and the attachment representations (SCPDP) of the 6-year-olds. Relying on the twofold distinction (secure/insecure), results revealed a significant continuity of attachment from 1 to 6 years of age, and a correspondence between maternal AAI and child's attachment quality in SS, as well as a correspondence between maternal AAI and the 6-year-olds' attachment representations. Using configural frequency analysis, we found continuity in patterns of security and insecurity when looking across the measures of infant and pre-school attachment and maternal adult attachment. Processes underlying the high match of mothers' and children's attachment representations are discussed.