Pathology of congenital Zika syndrome in Brazil: a case series

Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection.

Filtration to reduce paediatric dose for a linear slot-scanning digital X-ray machine.

This paper describes modelling, application and validation of a filtration technique for a linear slot-scanning digital X-ray system to reduce radiation dose to paediatric patients while preserving diagnostic image quality. A dose prediction model was implemented, which calculates patient entrance doses using variable input parameters. Effective dose is calculated using a Monte Carlo simulation. An added filter of 1.8-mm aluminium was predicted to lower the radiation dose significantly. An objective image quality study was conducted using detective quantum efficiency (DQE). The PTW Normi 4FLU test phantom was used for quantitative assessment, showing that image contrast and spatial resolution were maintained with the proposed filter. A paediatric cadaver full-body imaging trial assessed the diagnostic quality of the images and measured the dose reduction using a 1.8-mm aluminium filter. Assessment by radiologists indicated that diagnostic quality was maintained with the added filtration, despite a reduction in DQE. A new filtration technique for full-body paediatric scanning on the Lodox Statscan has been validated, reducing entrance dose for paediatric patients by 36 % on average and effective dose by 27 % on average, while maintaining image quality.

Twelve-month experience with the GORE® TIGRIS® Vascular Stent in the superficial femoral and popliteal arteries.

AIM: The aim of this paper was to report the continued mid-term follow-up of the first patients world-wide treated with the GORE(®) TIGRIS(®) Vascular Stent, a dual component stent consisting of a nitinol wire frame combined with a fluoropolymer-interconnecting structure. METHODS: From December 2011 until November 2012, 32 consecutive patients (20 men, mean age 72.8 years) with 40 atherosclerotic femoropopliteal lesions (5% occlusions) underwent angioplasty and implantation of a GORE(®) TIGRIS(®) Vascular Stent. The patients were scheduled for follow-up at 3, 6 and 12 months after stent implantation for duplex ultrasound and assessment of Rutherford-Becker class (RBC) and Ankle-Brachial Index (ABI). Here we report the completed 6-month follow-up and, for the first time, a 12-month follow-up. RESULTS: The median follow-up was 418 days. During the 12-month follow-up 4 patients died. Restenosis or reocclusion of the stent in this time period was observed in 5 lesions (12.5%), resulting in a cumulative primary patency rate of 85.5±6.0%. The ABI increased pre-interventionally from 0.65±0.18 to 0.91±0.18 (P<0.0001) at the 12-month visit. The median RBC improved from 3 to 1 (P<0.0001). No stent thrombosis related to discontinuation of dual antiplatelet therapy 4 weeks after the index procedure was observed. CONCLUSION: The mid-term follow-up of the dual component GORE(®) TIGRIS(®) Vascular Stent showed promising results with high 12-month primary patency rates after femoropopliteal endovascular interventions. These first clinical data are very promising compared to other stent concepts in the superficial femoral and popliteal artery.

Barriers and strategies for the clinical translation of advanced orthopaedic tissue engineering protocols.

Research in orthopaedic tissue engineering has intensified over the last decade and new protocols continue to emerge. The clinical translation of these new applications, however, remains associated with a number of obstacles. This report highlights the major issues that impede the clinical translation of advanced tissue engineering concepts, discusses strategies to overcome these barriers, and examines the need to increase incentives for translational strategies. The statements are based on presentations and discussions held at the AO Foundation-sponsored symposium "Where Science meets Clinics 2013" held at the Congress Center in Davos, Switzerland, in September, 2013. The event organisers convened a diverse group of over one hundred stakeholders involved in clinical translation of orthopaedic tissue engineering, including scientists, clinicians, healthcare industry professionals and regulatory agency representatives. A major point that emerged from the discussions was that there continues to be a critical need for early trans-disciplinary communication and collaboration in the development and execution of research approaches. Equally importantly was the need to address the shortage of sustained funding programs for multidisciplinary teams conducting translational research. Such detailed discussions between experts contribute towards the development of a roadmap to more successfully advance the clinical translation of novel tissue engineering concepts and ultimately improve patient care in orthopaedic and trauma surgery.

In vivo and protease-activated receptor-1-mediated platelet activation but not response to antiplatelet therapy predict two-year outcomes after peripheral angioplasty with stent implantation.

Data linking the response to antiplatelet therapy with clinical outcomes after angioplasty and stenting for lower extremity artery disease (LEAD) are scarce. Moreover, associations of in vivo and thrombin-inducible platelet activation with the occurrence of adverse events have not been investigated in these patients, so far. We therefore assessed clinical outcomes and on-treatment platelet reactivity by four test systems in 108 patients receiving dual antiplatelet therapy after infrainguinal angioplasty and stenting for LEAD. Further, in vivo and thrombin receptor-activating peptide (TRAP)-6-inducible glycoprotein (GP) IIb/IIIa activation and P-selectin expression were measured as sensitive parameters of platelet activation. The primary endpoint was defined as the composite of atherothrombotic events and target vessel restenosis or reocclusion. Residual platelet reactivity to adenosine diphosphate and arachidonic acid was similar between patients without and with adverse outcomes within two-year follow-up (all p>0.05). Further, the occurrence of clinical endpoints did not differ significantly between patients without and with high on-treatment residual platelet reactivity by all test systems (all p>0.05). In contrast, in vivo and TRAP-6-inducible platelet activation were significantly more pronounced in patients with subsequent adverse events (all p<0.05), and high levels of platelet activation were independent predictors of the primary endpoint (adjusted hazard ratios: 3.5 for high in vivo activated GPIIb/IIIa, 2.9 for high TRAP-6-inducible activated GPIIb/IIIa, 2.3 for high in vivo P-selectin, and 3 for high TRAP-6-inducible P-selectin; all p<0.05). In conclusion, in vivo and protease-activated receptor-1-mediated platelet activation predict two-year clinical outcomes in stable patients undergoing angioplasty and stenting for LEAD.

SS18-SSX fusion protein-induced Wnt/ß-catenin signaling is a therapeutic target in synovial sarcoma.

Synovial sarcoma is a high-grade soft tissue malignancy characterized by a specific reciprocal translocation t(X;18), which leads to the fusion of the SS18 (SYT) gene to one of three SSX genes (SSX1, SSX2 or SSX4). The resulting chimeric SS18-SSX protein is suggested to act as an oncogenic transcriptional regulator. Despite multimodal therapeutic approaches, metastatic disease is often lethal and the development of novel targeted therapeutic strategies is required. Several expression-profiling studies identified distinct gene expression signatures, implying a consistent role of Wnt/ß-catenin signaling in synovial sarcoma tumorigenesis. Here we investigate the functional and therapeutic relevance of Wnt/ß-catenin pathway activation in vitro and in vivo. Immunohistochemical analyses of nuclear ß-catenin and Wnt downstream targets revealed activation of canonical Wnt signaling in a significant subset of 30 primary synovial sarcoma specimens. Functional aspects of Wnt signaling including dependence of Tcf/ß-catenin complex activity on the SS18-SSX fusion proteins were analyzed. Efficient SS18-SSX-dependent activation of the Tcf/ß-catenin transcriptional complex was confirmed by TOPflash reporter luciferase assays and immunoblotting. In five human synovial sarcoma cell lines, inhibition of the Tcf/ß-catenin protein-protein interaction significantly blocked the canonical Wnt/ß-catenin signaling cascade, accompanied by the effective downregulation of Wnt targets (AXIN2, CDC25A, c-MYC, DKK1, CyclinD1 and Survivin) and the specific suppression of cell viability associated with the induction of apoptosis. In SYO-1 synovial sarcoma xenografts, administration of small molecule Tcf/ß-catenin complex inhibitors significantly reduced tumor growth, associated with diminished AXIN2 protein levels. In summary, SS18-SSX-induced Wnt/ß-catenin signaling appears to be of crucial biological importance in synovial sarcoma tumorigenesis and progression, representing a potential molecular target for the development of novel therapeutic strategies.

Effect of aluminium filtration on dose and image quality in paediatric slot-scanning radiography.

This paper examines the effect that a 1.8 mm aluminium filter has on paediatric patient dose and image quality for linear slot scanning radiography (LSSR). A dynamic dose prediction model for LSSR accurately predicted the dose reduction effects of added aluminium filtration. A cadaver imaging study was carried out to assess the effects of filtration on image quality. With 1.8 mm added aluminium filtration, no visible degradation to image contrast or clarity was found, and in some cases the aluminium filtration improved the image quality as judged by radiologists.

Genetic risk for nicotine dependence in the cholinergic system and activation of the brain reward system in healthy adolescents.

Genetic variation in a genomic region on chromosome 15q25.1, which encodes the alpha5, alpha3, and beta4 subunits of the cholinergic nicotinic receptor genes, confers risk to smoking and nicotine dependence (ND). Neural reward-related responses have previously been identified as important factors in the development of drug dependence involving ND. Applying an imaging genetics approach in two cohorts (N=487; N=478) of healthy non-smoking adolescents, we aimed to elucidate the impact of genome-wide significant smoking-associated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster on reward-related neural responses in central regions such as the striatum, orbitofrontal and anterior cingulate cortex (ACC), and personality traits related to addiction. In both samples, carriers of the rs578776 GG compared with AG/AA genotype showed a significantly lower neural response to reward outcomes in the right ventral and dorsal ACC but not the striatum or the orbitofrontal cortex. Rs578776 was unrelated to neural reward anticipation or reward magnitude. Significantly higher scores of anxiety sensitivity in GG compared with AG/AA carriers were found only in sample 1. Associations with other personality traits were not observed. Our findings suggest that the rs578776 risk variant influences susceptibility to ND by dampening the response of the ACC to reward feedback, without recruiting the striatum or orbitofrontal cortex during feedback or anticipation. Thus, it seems to have a major role in the processing of and behavioral adaptation to changing reward outcomes.

Enhanced mobilization of the bone marrow-derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction.

Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. We analysed in a randomized controlled study the influence of the intracoronary autologous freshly isolated BMCs-Tx on the mobilization of bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with acute myocardial infarction (AMI). Sixty-two patients with AMI were randomized to either freshly isolated BMCs-Tx or to a control group without cell therapy. Peripheral blood (PB) concentrations of CD34/45(+) - and CD133/45(+)-circulating progenitor cells were measured by flow cytometry in 42 AMI patients with cell therapy as well as in 20 AMI patients without cell therapy as a control group on days 1, 3, 5, 7, 8 and 3, 6 as well as 12 months after AMI. Global ejection fraction (EF) and the size of infarct area were determined by left ventriculography. We observed in patients with freshly isolated BMCs-Tx at 3 and 12 months follow up a significant reduction of infarct size and increase of global EF as well as infarct wall movement velocity. The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased with a peak on day 7 as compared to baseline after AMI in both groups (CD34/45(+): P < 0.001, CD133/45(+): P < 0.001). Moreover, this significant mobilization of BM-CPCs existed 3, 6 and 12 months after cell therapy compared to day 1 after AMI. In control group, there were no significant differences of CD34/45(+) and CD133/45(+) BM-CPCs mobilization between day 1 and 3, 6 and 12 months after AMI. Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system in patients with AMI may enhance and prolong the mobilization of CD34/45(+) and CD133/45(+) BM-CPCs in PB and this might increase the regenerative potency after AMI.

[Prevalence and clinical significance of incidental cardiac findings in non-ECG-gated chest CT scans]. / Prävalenz und klinische Bedeutung inzidenteller Herzbefunde im nicht EKG-getriggerten Thorax-CT.

BACKGROUND: The purpose of this study was to evaluate the prevalence and clinical significance of incidental cardiac findings in non-ECG-gated chest CT. PATIENTS AND METHODS: Non-ECG-gated chest CT examinations of 300 patients were retrospectively analyzed for incidental cardiac findings. Subsequently, these findings were evaluated for their clinical relevance by a cardiologist. RESULTS: A total of 107 out of 300 examined patients had 174 incidental cardiac findings including coronary calcification (90), aortic/mitral valve calcification (42), iatrogenic changes (23), pericardial effusion (6), dilatation of the heart (4), myocardial changes (3), thrombus in the left ventricle (2), constrictive pericarditis (2) and atrial myxoma (1). Of the cardiac findings 51% were described in the written report and in 53 out of the 107 patients the cardiac findings were unknown. Newly detected incidental findings from 8 patients were rated as clinically significant: pericardial effusion (4), constrictive pericarditis (1), thrombus in the left ventricle (1), atrial myxoma (1) and dilatation of the heart (1). CONCLUSION: Incidental cardiac findings are frequent in non-ECG-gated chest CT and may have a high clinical relevance.

Improved functional activity of bone marrow derived circulating progenitor cells after intra coronary freshly isolated bone marrow cells transplantation in patients with ischemic heart disease.

OBJECTIVES: There is growing evidence that intracoronary autologous bone marrow cells transplantation (BMCs-Tx) in patients with chronic myocardial infarction beneficially affects postinfarction remodelling. In this randomized controlled study we analyzed the influence of intracoronary autologous freshly isolated bone marrow cells transplantation by use of point of care system on cardiac function and on the functional activity of bone marrow derived circulating progenitor cells (BM-CPCs) in patients with ischemic heart disease (IHD). METHODS: 56 patients with IHD were randomized to either received freshly isolated BMC-Tx or a control group that did not receive cell therapy. The functional activity of BM-CPCs in peripheral blood (PB) was measured by migration assay and colony forming unit assay pre- and 3, 6 as well as 12 months after procedure. Global ejection fraction (EF) and infarct size area were determined by left ventriculography. RESULTS: Intracoronary transplantation of autologous freshly isolated BMCs led to a significant reduction of infarct size and an increase of global EF as well as infarct wall movement velocity after 3 and 12 months follow-up compared to control group. The colony-forming capacity of BM-CPCs significantly increased 3, 6 and 12 months after cell therapy compared to pre BMCs-Tx and control group (CFU-E: p < 0.001, CFU-GM: p < 0.001). Likewise, we found significant increase of migratory response to stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) after cell therapy compared to pre BMCs-Tx (SDF-1: p < 0.001, VEGF: p < 0.001) and to control (SDF-1: p < 0.001, VEGF: p < 0.001). There was no significant difference of migratory- and colony forming capacity between pre- and 3, 6, 12 months after coronary angiography in control group without cell therapy. CONCLUSIONS: Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system may lead to improvement of BM-CPCs functional activity in peripheral blood, which might increase the regenerative potency in patients with IHD.

The distribution of seagrasses in Dominica, Lesser Antilles

Seagrass beds are the largest organism-built marine habitat in Dominica, yet have only been surveyed since 2007. Standardized examinations along a depth gradient between 0 and 24m, focusing on magnoliophyte species composition and benthic cover of shoots at 17 seagrass bed sites, were carried out between September 10 and December 7, 2008. The Cymodoceaceae Syringodium filiforme (Kuetzing 1860) and Halodule wrightii (Ascherson 1868), as well as the Hydrocharitaceae Halophila decipiens (Ostenfeld 1902), H. stipulacea (Fosskal & Ascherson 1867) and Thalassia testudinum (Banks ex König 1805) displayed distinct regional and horizontal distribution patterns. Syringodium filiforme is the island’s dominant seagrass along the western and northern coasts, occurring at depths between 2 and 18m and with a mean benthic cover ranging from 0.9-10% along the West coast. Along the North coast it grew between 0.2 and 1m depth with a mean maximum benthic cover of 48.9%. Halodule wrightii grew along the North and West coasts, in depths between 1 and 14m in areas of recent and chronic disturbances. Its delicate morphology and sparse benthic cover (<0.1%) did not constitute seagrass beds. Halophila decipiens grew along the deep, shallow and lateral margins of west coast S. filiforme beds and monospecifically in depths between 3 and 24m. Halophila stipulacea, an invasive species, was widespread along 45km of the West coast and was found in depths between 5 and 24m. Both Halophila species formed extensive beds at depths beyond the survey limit of 24m thus playing a potentially important role in the resettlement of shallow areas after storms. H. decipiens and H. stipulacea are currently the second and third most common seagrasses on the island respectively, despite their absence along the North coast. T. testudinum was confined to North coast’s sheltered reef flats at depths 1m or less with mean a benthic cover ranging from 2 to 76%. It grew monospecifically in the most turbulent and in the calmest locations, yet intermixed with S. filiforme in areas of moderate turbulence. Strong surge along the West coast (October 15-16, 2008), associated with Hurricane Omar, caused uprooting and burial of seagrass beds in varying degrees, in particular along the shallow margins between 2 and 10m depth. This event also demonstrated the dynamic nature of Dominica’s shallow seagrass bed margins and the resistance level of individual beds to storm disturbances. Rev. Biol. Trop. 58 (Suppl. 3): 89-98. Epub 2010 October 01.

Pastos marinos son los ambientes más grandes constituidos por organismos en Dominica. Sin embargo, sólo se han examinado desde 2007. Entre el 10 de septiembre y 9 de diciembre 2008, se examinaron la composicion de especies y la densidad de magnoliofitas en profundidades de 0 a 24m. Los Cymodoceaceae: Syringodium filiforme y Halodule wrightii, tal como los Hydrocharitaceae: Halophila decipiens, H. stipulacea y Thalassia testudinum, mostraron una distribución regional y horizontal muy distinta. Syringodium filiforme fue la especie dominante en las costas del oeste y del norte de la isla. Se encontró en profundidades de 2 a 18m y con un promedio de cobertura béntica de 0.9-10% en la costa del oeste. En las costas del norte creció entre 0.2 y 1m de profundidad con un pormedio de cobertura béntica de 48.9%. Halodule wrightii creció en las costad del norte y oeste, en profundidades de 1 a 14m en áreas de perturbaciones recientes o crónicas. Su morfología delicada y su baja cobertura béntica (<0.1%) no constituyeron pastos. Halophila decipiens creció en los márgenes profundos, llanos y laterales de pastos dominados por S. filiforme, pero también en forma mono-específica entre 3 y 24m. Halophila stipulacea, una especie invasora, se encontró comúnmente a lo largo de 45km de la costa del oeste en profundidades entre 5 y 24m. Ambas especies de Halophila formaron pastos extensos en profudidades mayores al límite de este estudio y puden ser importantes en la recolonización de áreas llanas después de tormentas destructivas. H. decipiens y H. stipulacea ahora son las especies más comunes después de S. filiforme, a pesar de su ausencia en la costa del norte. T. testudinum, sólo creció en la costa del norte, encima de áreas arrecifales con un pormedio de cobertura béntica entre 2 y 76%, en aguas con 1m o menos de profundidad. Crecieron mono-específicamente en áreas de turbulencia máxima y mínima, pero entre S. filiforme en áreas de turbulencia moderada. Oleaje fuerte en la costa del oeste (octubre 16), asociado con el Huracán Omar, causó la erosión y el enterramiento variado de las márgenes llanas de pastos marinos, particularmente entre 2 y 10m de profundidad. Este evento demostró la dinámica en las márgenes llanas de pastos marinos de Dominica y el nivel de resistencia a perturbaciones de pastos individuales.

Reduction of both number and proliferative activity of human endothelial progenitor cells in obesity.

OBJECTIVE: Circulating endothelial progenitor cells (EPCs), responsible for neoangiogenesis and vascular repair, negatively correlate with vascular dysfunction and atherosclerotic risk factors. Because obesity may have a crucial role in the development of endothelial dysfunction, this study evaluated the number and proliferative activity of circulating human EPCs in obese (body mass index (BMI)=48+/-9, n=45) compared with lean (23+/-2, n=45) volunteers. METHODS: EPCs were quantified after isolation of peripheral blood mononuclear cells (PBMCs) using fluorescence-activated cell sorting analyses. In addition, plated PBMCs developed colony-forming units (CFUs) from which 'outgrowth' endothelial cells (OECs) sprouted and differentiated into mature endothelial cells. Growth rates were monitored by periodical microscopic evaluation. Cell-cycle protein expression was determined by western blot analyses. RESULTS: BMI negatively correlated (P<0.01) with the number of CD34(+)/CD133(+)/KDR(+) (r=-0.442), CD34(+)/KDR(+) (r=-0.500) and CD133(+)/KDR(+) (r=-0.282) EPCs. Insulin, leptin, HbA(1c), high-sensitivity C-reactive protein and hypertension, as well as diminished high-density lipoprotein and apolipoprotein A1, were not only associated with obesity but also with significantly reduced EPC levels. Applying selective culture conditions, EPC-CFUs differentiated into OECs that proliferated more slowly when derived from obese compared with lean subjects (obese: 19.9+/-2.2% vs lean: 30.9+/-3.2% grown area per week, P<0.01). The reduced proliferation was reflected by decreased (P<0.05, n=24 for each group) expression of cell-cycle-promoting cyclins and E2F-1, by hypophosphorylation of retinoblastoma protein and by increased (P<0.05, n=24 for each group) expression of the cell-cycle inhibitor p21(WAF-1/Cip1). CONCLUSIONS: Reduced numbers of EPCs along with their premature senescence, as shown in this study, could function as early contributors to the development and progression of vascular dysfunction in obesity.

Adenosine diphosphate-inducible platelet reactivity shows a pronounced age dependency in the initial phase of antiplatelet therapy with clopidogrel.

BACKGROUND: Until recently, there were hardly any data on the antiplatelet effect of clopidogrel in advanced age. Like other metabolic processes, the conversion of clopidogrel to its active metabolite may be impaired in older patients, leading to high on-treatment residual ADP-inducible platelet reactivity. OBJECTIVE: To investigate the age dependency of clopidogrel-mediated platelet inhibition. PATIENTS AND METHODS: This was a prospective observational study. We determined adenosine 5'-diphosphate (ADP)-inducible platelet reactivity using light transmission aggregometry (LTA) and the VerifyNow P2Y12 assay in 191 patients on dual antiplatelet therapy after angioplasty and stenting for cardiovascular disease. RESULTS: ADP-inducible platelet reactivity increased linearly with age after adjustment for cardiovascular risk factors, type of intervention, medication, C-reactive protein (CRP) and renal function [using LTA 0.36% of maximal aggregation per year, 95% CI 0.08-0.64%, P = 0.013; using the VerifyNow P2Y12 assay 3.2 P2Y12 reaction units (PRU) per year, 95% CI 1.98-4.41 PRU, P < 0.001]. ADP-inducible platelet reactivity was significantly higher in patients aged 75 years or older compared with younger patients (P = 0.003 for LTA and P < 0.001 for the VerifyNow P2Y12 assay). Further, high on-treatment residual ADP-inducible platelet reactivity was significantly more common among patients aged 75 years or older (P = 0.02 for LTA and P < 0.001 for the VerifyNow P2Y12 assay). CONCLUSION: ADP-inducible platelet reactivity shows a pronounced age dependency in the initial phase of antiplatelet therapy with clopidogrel. The clinical implications of these findings need to be addressed in future trials.

[Multiple peritonsillar abscesses caused by Arcanobacterium haemolyticum in a young female]. / Multiple Peritonsillarabszesse durch Arcanobacterium haemolyticum bei einer jungen Frau.

HISTORY: A 20-year-old previously healthy woman presented with a four-week history of sore throat and inability to swallow. INVESTIGATION AND DIAGNOSIS: Initial examination revealed tender swelling and exudation of both palatine tonsils, trismus and bilateral cervical lymphadenopathy. Laboratory tests showed leukocytosis, elevated C-reactive protein, but unremarkable Epstein-Barr virus titers. COURSE AND TREATMENT: The patient was unsuccessfully treated for three days with topical antiseptics and systemic cefuroxime. Cervical magnetic resonance tomography (MRT) disclosed multiple peritonsillar abscesses. For this reason a bilateral tonsillectomy was performed. Aerobic cultures of the surgical specimens revealed the exclusive presence of Arcanobacterium haemolyticum. The patient's condition improved rapidly after surgery, with continued administration of cefuroxim. CONCLUSIONS: Peritonsillar abscesses are potentially life-threatening complications of a pharyngitis or tonsillitis. Regularly, a mixed microbial flora including Staphylococcus aureus or Streptococcus pyogenes and anaerobic bacteria such as Fusobacterium can be isolated from abscess material. Because of the virulence of the involved microorganisms and the proximity of the jugular vein and the carotid sheath, Lemierre syndrome may develop (throat infection followed by anaerobic septicaemia). Arcanobacterium haemolyticum is responsible for fewer than one percent of all pharyngotonsillitis cases. The infection is clinically indistinguishable from S. pyogenes or Epstein-Barr virus infections. Any removed specimen should be cultured on media supporting growth of fastidious bacteria and under both aerobic and anaerobic conditions. Because of its inconspicuous colony morphology, Arcanobacterium may be wrongly identified as physiological microflora and it is therefore probably underreported as a cause of pharyngotonsillitis and associated complications.

[Malignant mixed Müllerian tumor of the urinary bladder]. / Maligner Müller-Mischtumor der Harnblase.

True mixed epithelial-mesenchymal tumors of the urinary bladder are exceedingly rare, and only two vesical adenosarcomas have been reported to date. These tumors originated from bladder endometriosis, and malignant transformation of endometriosis has been described, with endometrioid and clear-cell carcinomas being the most common malignancies. We report an unusual case of a malignant mixed Müllerian tumor with heterologous rhabdomyoblastic differentiation, which originated in the urinary bladder of a postmenopausal woman. To the best of our knowledge, such a neoplasm has not yet been reported in the literature.

Long-term non-surgical therapy of severe persistent congenital hyperinsulinism with glucagon.

BACKGROUND: Congenital hyperinsulinism (CHI) is characterized by severe hypoglycemia caused by dysregulated insulin secretion. The long-term outcome is dependent on prevention of hypoglycemic episodes to avoid the high risk of permanent brain damage. Severe cases are usually resistant to diazoxide or nifedipine. In addition, somatostatin analogues are ineffective in a subgroup of patients to achieve stable euglycemia. In these infants the only remaining long-term option has been subtotal pancreatectomy with high risk of diabetes mellitus. Intravenous infusions of glucagon are used as immediate treatment to stabilize euglycemia in affected newborns. The rationale of this treatment comes from the observation of an increased glycogen content of the liver when glycogenolysis is inhibited by insulin. OBJECTIVE: To review the efficacy and safety of long-term subcutaneous glucagon infusion as a potential therapeutic option for blood glucose stabilization in infants with severe CHI without the need of additional intravenous glucose or immediate surgical intervention. METHOD: Retrospective review of 9 children with CHI who received continuous subcutaneous infusion of glucagon for weeks or months. Glucagon was added to octreotide to replace octreotide-induced suppression of endogenous glucagon secretion, thereby liberating glucose by stimulation of hepatic glycogenolysis. In 3 cases, a stabilized formulation of glucagon was used to prevent glucagon crystallization that frequently occurs in smaller volumes. RESULTS: Introduction of glucagon allowed the reduction or discontinuation of central glucose infusion in all children studied. In 2 patients, glucagon was introduced due to recurrent hypoglycemia despite subtotal pancreatectomy. Six out of 9 children were discharged home on this treatment, which their parents were able to continue without further symptomatic hypoglycemia, convulsions or unconsciousness. In 3 children, subcutaneous glucagon was continuously administered for 1-4 years leading to stable euglycemia. However, 2 children with diffuse type still required subtotal pancreatectomy. As a possible side effect, 2 children developed erythema necrolyticum, which resolved after discontinuation of the glucagon infusion. This has been described before in glucagonoma. CONCLUSION: In this retrospective series, combination therapy of low-dose octreotide and subcutaneous glucagon infusion has been effective in preventing hypoglycemic episodes in severe CHI. We propose this may serve as a therapeutic option in place of high rates of glucose infusion through a central venous catheter and as an alternative to subtotal pancreatectomy in diffuse type of CHI.

Factors influencing spontaneous mobilization of CD34+ and CD133+ progenitor cells after myocardial infarction.

BACKGROUND: Bone marrow-derived circulating progenitor cells (BM-CPCs) are mobilized into adult peripheral blood (PB) during acute myocardial infarction (AMI) and may contribute to the regeneration of infarcted myocardium. The purpose of the present study is to determine whether mobilization of BM-CPCs into PB depends on cardiovascular risk factors (CVRFs), age of patients, infarct associated inflammatory markers, and left ventricular function after AMI. MATERIALS AND METHODS: Peripheral blood concentrations of CD34/45(+) and CD133/45(+) BM-CPCs were measured by flow cytometry in 44 patients after AMI and in 16 subjects with atypical chest pain acting as controls. RESULTS: Mobilization of CD34/45(+) and CD133/45(+) BM-CPCs on day 1 after AMI showed significant negative correlation with age, the number of CVRFs, infarct size, creatine phosphokinase peak in bivariate as well as in multivariate analyses. We additionally found a positive correlation of CD34/45(+) and CD133/45(+) BM-CPCs mobilization on day 1 after AMI with global ejection fraction (EF) in bivariate analysis but could not confirm this in multivariate analysis. Elevated of C-reactive protein (CRP) and leukocyte levels on day 1 after AMI were significantly associated with decreased concentrations of CD34/45(+) BM-CPCs. The concentrations of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased in AMI patients, with the peak on day 7 as compared to the control group. CONCLUSIONS: The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs into the PB depends on many factors, i.e. the number of CVRFs, age, infarct size and inflammatory markers of patients. Most importantly, the severity of the circulatory dysfunction and the amount of necrotic myocardial tissue are the main determinants. Moreover, this spontaneous mobilization of BM-CPCs may serve as a very important surrogate for infarct size as well as for global EF and it may determine the regenerative potency after AMI.

Immunohistochemical expression patterns of AP2alpha and AP2gamma in the developing fetal human breast.

AIMS: AP2alpha (TFAP2A) and AP2gamma (TFAP2G) transcription factors have been implicated in the control of proliferation, differentiation and apoptosis of normal breast epithelium and in breast cancer. The aim of this study was to provide a comprehensive analysis of the expression patterns of TFAP2A and TFAP2G in the developing fetal breast anlage with other relevant markers. METHODS AND RESULTS: Sixty fetal and one infant human breast specimens from 14 weeks of gestational age to 5 months old were examined. The primary breast outgrowth/nipple showed TFAP2A expression by the basal cells (week 14), followed later by cytokeratin (CK) 5 co-expression (week 17). Sprouting of the secondary outgrowths was characterized by HER-2+ invading cells. Preliminary ductal buds were lined by TFAP2G/HER-1-expressing myoepithelial precursors (week 19). Maturation of TFAP2A/CK18+ epithelia and TFAP2G/smooth muscle actin-positive myoepithelia proceeded in a distal-to-proximal manner beginning in the terminal end buds (week 22). CK5+ progenitor cells and CK5/TFAP2A or CK5/TFAP2G co-expressing intermediary glandular or myoepithelial cells were found in the terminal end buds of neonatal fetal breast tissue. CONCLUSIONS: AP2 transcription factors may play decisive pacemaker roles in initiating and coordinating budding and branching processes during formation of the fetal breast anlage, possibly via modulation of an epidermal growth factor receptor.

Diagnostics in pulmonary hypertension.

Pulmonary hypertension is a serious disease with a poor prognosis. Pulmonary hypertension is defined by a mean pulmonary arterial pressure over 25 mm Hg at rest or over 30 mm Hg during activity. According to the recent WHO classification from 2003 pulmonary hypertension can be categorized as pulmonary arterial hypertension, pulmonary venous hypertension, hypoxic pulmonary hypertension, chronic thromboembolic pulmonary hypertension and pulmonary hypertension from other causes. Pulmonary arterial hypertension is characterized histopathologically by vasoconstriction, vascular proliferation, in situ thrombosis, and remodeling of all 3 levels of the vascular walls. These pathologic changes result in progressive increases in the mean pulmonary artery pressure and pulmonary vascular resistance, which, if untreated leads to right-ventricular failure and death. Early in the disease process, the signs and symptoms of PAH are often nonspecific, making diagnosis challenging. Patients often present with progressively worsening dyspnea and fatigue. Patients with severe pulmonary arterial hypertension die of right heart failure. The diagnostic procedures include clinical history and physical examination, a standard chest radiography, electrocardiography, transthoracic Doppler echocardiography, pulmonary function tests, arterial blood gas analysis, ventilation and perfusion lung scan, high-resolution computed tomography of the lungs, contrast-enhanced spiral computed tomography of the lungs and pulmonary angiography, blood tests and immunology, abdominal ultrasound scan, exercise capacity assessment, and hemodynamic evaluation. Invasive and non-invasive markers of disease severity, either biomarkers or physiological parameter and tests that can be widely applied, have been proposed to reliably monitor the clinical course. Pulmonary biopsy is rarely indicated. Transthoracic echocardiography is a key screening tool in the diagnostic algorithm. Because transthoracic echocardiography is an inexpensive, easy, and reproducible method, it is the most commonly used noninvasive diagnostic tool to determine pulmonary arterial pressure. But it not only provides an estimate of pulmonary pressure at rest and during exercise, but it may also help to exclude any secondary causes of pulmonary hypertension, predict the prognosis, monitor the efficacy of specific therapeutic interventions, and detect the preclinical stage of the disease. In addition, the measurement of serum markers, such as brain natriuretic peptide (BNP), are diagnostically useful and of prognostic significance. Once the diagnosis and etiology of pulmonary hypertension have been established, several parameters can predict outcome in these patients: functional class, right ventricular function, pulmonary hemodynamics, and certain laboratory parameters. Also, exercise parameters such as walking distance, peak oxygen uptake or peak systolic blood pressure can reliable predict prognosis in these patients.