Variation in the TEK gene is not associated with asthma but with allergic conjunctivitis.

The Tie2 receptor is an important player in angiogenesis. The Tie2 mRNA and protein are abundantly expressed in the lungs and the associated pathway also has an important role in the development and function of the eye. Tie2 is encoded by the TEK gene in humans. Recently, variations in the TEK gene have been found associated with asthma. The objective of the present study was to investigate whether variations in the TEK gene influenced the susceptibility to pediatric asthma and/or associated phenotypes like GINA status, viral- or exercise-induced asthma, allergic asthma, indoor, outdoor, inhalative allergies, IgE and eosonophil levels, allergic rhinitis and allergic conjunctivitis. Three single nucleotide polymorphisms (SNPs, rs3780315, rs581724 and rs7876024) in the TEK gene were genotyped in 1189 unrelated individuals, out of which 435 were asthmatic children and 754 healthy controls. Different types of asthma, allergies and co-morbidities were defined in 320 patients. Among the fully phenotyped 320 asthmatic patients 178 (55.6%) also had allergic rhinitis and 100 (31.3%) had conjunctivitis. Among the rhinitis patients 98 (55.1%) also had conjunctivitis. Two patients had conjunctivitis without rhinitis. The genotyped SNPs showed no association with asthma. However, SNP rs581724 was significantly associated with allergic conjunctivitis in a recessive way (p=0.007; OR=2.3 (1.3-4.4)) within the asthmatic population. The risk remained significant when the whole population (asthmatics and healthy controls) was included in the calculation (p = 0.003; OR = 2.1 (1.3-3.6)). The minor allele of the rs581724 SNP which is associated with the increased risk to conjunctivitis is also associated with reduced Tie2 expression. There was a significant association between SNP rs581724 and the occurrence of allergic conjunctivitis in asthmatic children. If additional studies can confirm the role of the Tie2 pathway in allergic conjunctivitis, it can be a potential novel therapeutic target in the disease.

Altered neurite morphology and cholinergic function of induced pluripotent stem cell-derived neurons from a patient with Kleefstra syndrome and autism.

The aim of the present study was to establish an in vitro Kleefstra syndrome (KS) disease model using the human induced pluripotent stem cell (hiPSC) technology. Previously, an autism spectrum disorder (ASD) patient with Kleefstra syndrome (KS-ASD) carrying a deleterious premature termination codon mutation in the EHMT1 gene was identified. Patient specific hiPSCs generated from peripheral blood mononuclear cells of the KS-ASD patient were differentiated into post-mitotic cortical neurons. Lower levels of EHMT1 mRNA as well as protein expression were confirmed in these cells. Morphological analysis on neuronal cells differentiated from the KS-ASD patient-derived hiPSC clones showed significantly shorter neurites and reduced arborization compared to cells generated from healthy controls. Moreover, density of dendritic protrusions of neuronal cells derived from KS-ASD hiPSCs was lower than that of control cells. Synaptic connections and spontaneous neuronal activity measured by live cell calcium imaging could be detected after 5 weeks of differentiation, when KS-ASD cells exhibited higher sensitivity of calcium responses to acetylcholine stimulation indicating a lower nicotinic cholinergic tone at baseline condition in KS-ASD cells. In addition, gene expression profiling of differentiated neuronal cells from the KS-ASD patient revealed higher expression of proliferation-related genes and lower mRNA levels of genes involved in neuronal maturation and migration. Our data demonstrate anomalous neuronal morphology, functional activity and gene expression in KS-ASD patient-specific hiPSC-derived neuronal cultures, which offers an in vitro system that contributes to a better understanding of KS and potentially other neurodevelopmental disorders including ASD.

Co-infection with Bovine Herpesvirus 4 and Histophilus somni Significantly Extends the Service Period in Dairy Cattle with Purulent Vaginal Discharge.

The aim of the study was to investigate the effect of Bovine Herpesvirus 4 (BoHV-4) and Histophilus (H.) somni on fertility rate of cows in a Hungarian Holstein-Friesian dairy herd with purulent vaginal discharge (PVD). Non-pregnant cows (n = 188) with mature corpus luteum were treated with cloprostenol and 3 days later if they did not show oestrus, were examined by rectal palpation. Animals showing PVD (n = 60/31.9%/) and 14 controls with normal vaginal discharge (Score 0) were randomly selected and further examined by ultrasonography and blood samples were collected for detecting BoHV-4 DNA and transcervical guarded swabs were collected from the uterus for bacteriological examination. Although the majority of the examined animals were infected with BoHV-4 and H. somni including the control animals as well, in group of animals with PVD score 3, fewer animals became pregnant and the duration between the first treatment to pregnancy was significantly extended. Based on these clinical and comparative data, our results confirm that these two microorganisms together may impair important reproductive parameters which may cause large economic losses to dairy farms.

PAIN OUT: the making of an international acute pain registry.

BACKGROUND: About 240 million patients undergo surgery every year, worldwide. Roughly 50% of these patients report clinically significant pain. Numerous barriers impede provision of adequate management. Lack of evidence about appropriateness and effectiveness of interventions is one. A registry can provide such information, eventually facilitating better management. This paper reports the development and feasibility of PAIN OUT, the first international acute pain registry, established with funds from the European Commission, and presents preliminary analysis to illustrate the nature of investigations that registry data make possible. METHODS: On the first postoperative day, 6347 adult patients undergoing orthopaedic or general surgery, in 11 medical centres in Europe and Israel, provided Patient Reported Outcomes (PROs) using a validated questionnaire. Clinical data were abstracted from the patient's chart. RESULTS: Feasibility worked well. Over a period of 1 year, surveyors accrued targeted data sets and entered them into an online browser. Collaborators could receive online feedback comparing their findings about PROs against anonymized findings from other centres. Missing data for the majority of variables were low. Despite considerable variability between institutions, a large number of patients were treated according to the generic, evidence-based recommendations we assessed. However, this was not sufficient to result in acceptable outcomes for the majority of patients. CONCLUSION: The initial development of PAIN OUT has been achieved. From 2013, it continues as a not-for-profit academic project, open to clinicians and researchers worldwide. The International Association for Study of Pain and PAIN OUT will work together to maintain, disseminate and develop the registry.

Improved experimental burn model on rabbits.

OBJECTIVE: The goal of our study was to find an easy and suitable skin burn model for rabbits, to identify the temperature and contact time to reach a deep 2nd degree burn, and to find the best wound dressing fixation method. MATERIAL AND METHODS: We used New Zealand male rabbits as experimental models. On a pilot study, with a copper device heated to temperatures between 43-48 Celsius degrees, the burn was inflicted using contact timesof 3, 4, 5, and 7 seconds. The burn depth was evaluated histological. Twenty-four rabbits were used to evaluate four dressing fixation methods: regular dressing with retention bandages; skin stapler; collars and body resin cast. RESULTS: A 2nd degree deep burn was obtained at 43 degrees for 4 seconds. The retention elastic bandages were removed within hours and the skin staplers were removed with teeth leaving wounds on the skin. The collars were more successful but produced superficial neck lesions. The body resin casts were the most successful. CONCLUSIONS: The best contention method was the bpdy resin cast.

Granulomatous cheilitis of Miescher: the diagnostic proof for a Melkersson-Rosenthal syndrome.

BACKGROUND: The Melkersson-Rosenthal syndrome (MRS) is a very rare clinical entity and its classical form is being characterized by the following triad: facial nerve palsy, swelling of the lips and fissured tongue. However, the monosymptomatic form is more common and the typical manifestation is facial edema and/or enlargement of the lips. CASE REPORT: We report a case of monosymptomatic MRS with a positive biopsy of granulomatous cheilitis. CONCLUSIONS: In the daily practice as a pediatrician, it is not usual to diagnose a patient as having MRS. We consider that this is partly because of misdiagnosis. We therefore believe that this case report will supply additional information, in the scope of recurrent facial paralysis and orofacial edema in both children and adults.

Sarcoid flexor tenosynovitis as a single early manifestation of the disease.

Sarcoid flexor tenosynovitis is rare. Isolated sarcoid tenosynovitis of the index finger in a young woman as an early manifestation of the disease is reported. Tenosynovectomy was performed as a therapeutic and diagnostic tool, followed by systemic corticosteroids. The patient had no signs of relapse 3 years after surgery.

Feasibility of international data collection and feedback on post-operative pain data: proof of concept.

Post-operative pain exacts a high toll from patients, families, healthcare professionals and healthcare systems worldwide. PAIN-OUT is a research project funded by the European Union's 7th Framework Program designed to develop effective, evidence-based approaches to improve pain management after surgery, including creating a registry for feedback, benchmarking and decision support. In preparation for PAIN-OUT, we conducted a pilot study to evaluate the feasibility of international data collection with feedback to participating sites. Adult orthopaedic or general surgery patients consented to participate between May and October 2008 at 14 collaborating hospitals in 13 countries. Project staff collected patient-reported outcomes and process data from 688 patients and entered the data into an online database. Project staff in 10 institutions met the enrolment criteria of collecting data from at least 50 patients. The completeness and quality of the data, as assessed by rate of missing data, were acceptable; only 2% of process data and 0.06% of patient-reported outcome data were missing. Participating institutions received access to select items as Web-based feedback comparing their outcomes to those of the other sites, presented anonymously. We achieved proof of concept because staff and patients in all 14 sites cooperated well despite marked differences in cultures, nationalities and languages, and a central database management team was able to provide valuable feedback to all.

New trends in breast reconstruction.

BACKGROUND: Breast reconstruction (BR) after radical mastectomy is intended to recreate symmetrical natural-appearing breasts while preserving patient safety and quality of life. PURPOSE: To evaluate the esthetic results and the complications of various BR methods after radical mastectomy. PATIENTS AND METHOD: Between August 2006 and March 2010, 36 women underwent BR after mastectomy in our institution. Their charts were reviewed retrospectively to evaluate the results and complications. We used immediate BR for Stage I and IIa breast carcinoma, and delayed BR for stage IIb and III breast carcinoma. RESULTS: We performed a pedicled Transverse Rectus Abdominis Muscle flap in 13 cases, pedicled Latissimus Dorsi with silicone implant in 10 cases, free Deep Inferior Epigastric Perforator (DIEP) flap in 9 cases, and other procedures in four cases. The encountered complications were: total flap failure--one case, partial edge flap necrosis--three cases, donor area wound dehiscence--one case, seroma--one case, local infection--one case. DISCUSSION: Trends in BR in recent years focus more on free perforator flaps, with the DIEP flap being the leader. Internal mammary vessels are most often used as recipient vessels for anasthomoses. Immediate BR when indicated has better aesthetic results. In less well-developed countries, insurance companies do not cover implant expenses and the autologous procedures remain the best option.

Brucellosis of the European brown hare (Lepus europaeus).

The European brown hare (Lepus europaeus) is an important reservoir of Brucella suis biovar 2 and also of the life-threatening zoonotic agent Francisella tularensis. Since both bacteria can produce similar gross pathological lesions in this species, laboratory tests are necessary for the final diagnosis. The aim of the present study was to develop an immunohistochemical method for the detection of B. suis infection and to describe the pathological and histological lesions caused by B. suis in European brown hares. Hyperimmune serum for immunohistochemistry (IHC) was produced by subcutaneous infection of mice with 2 × 10(9) colony forming units of live B. suis biovar 2, injected four times at 1-week intervals. The antiserum did not react with F. tularensis or Yersinia pseudotuberculosis in IHC and displayed only weak cross-reaction with B. canis. Numerous, yellow-white necrotic foci (0.1-0.5 cm diameter) were found in the spleen of five B. suis-infected female European brown hares and also in the lung, uterus, kidney or liver of four of these cases. Microscopically, the foci comprised single or coalescing granulomas with a central necrotic area. Both bacterial isolation and IHC gave positive results for B. suis infection in these animals. B. suis antigens were found as granular or amorphous extracellular material in the necrotic centre of several granulomas. IHC appears to be a suitable complementary diagnostic method for the detection of B. suis infection in the European brown hare.

Salvage of compromised free flaps in trauma cases with combined modalities.

Using the microsurgical technique for reconstruction in trauma cases represents a challenge for the reconstructive surgeon. Several methods of salvaging of a compromised free flap have been reported, among them: intravenous heparin washing, thrombolitic therapy, thrombectomy, use of grafts and others. Here, we present our experience from nine cases and a review of the literature regarding the use of various modalities for free flap salvage in trauma cases, and their results. Data was collected from trauma cases in our institutions over a period of 2 years, where reconstruction was performed using microsurgical techniques, and where subsequent complications required some type of salvage procedure. The techniques that were used for the salvage included: intravascular irrigation with heparin, papaverine and lidocaine; administration of continuous intravenous heparin, use of the Fogarty catheter, flap washing with streptokinase, and adventitia stripping. The free flaps used were latissimus dorsi, serratus anterior, and the anteromedial thigh flap. Either vein or artery thromboses were identified during the procedure or immediately after surgery in seven patients. Two patients had prolonged spasms of the recipient artery with low flow. In all cases, the No. 2 Fogarty catheter was used for thrombectomy and also for release of the vessel spasm. There was only one complete failure among these patients, and partial necrosis was encountered in three. From our experience and review of the literature, we offer an algorithm for determining treatment strategies in a range of flap salvage situations.

Severe compartment syndrome following fibula harvesting for mandible reconstruction.

There are many reports of the use of free fibular flap for mandible reconstruction, but donor site morbidity is not uncommon. The authors present the case of a 52-year-old man who underwent mandible reconstruction with free fibular flap. After surgery, he developed severe compartment syndrome involving all four-calf compartments. Debridement of the necrotic areas was followed by posterior nerve neurolysis and soft tissue coverage with free latissimus dorsi and anterior serratus muscle flaps. The postoperative period was uneventful and the patient remained with diminished plantar sensation 1 year later. Compartment syndrome after fibula harvesting is a possibility and should be recognized as soon as possible in order to limit extensive damage to the calf muscles and nerves.

Tularemia of European Brown Hare (Lepus europaeus): a pathological, histopathological, and immunohistochemical study.

The European brown hare (Lepus europaeus) plays an important role in the ecology of tularemia, and it may serve as a significant source of human infection. The aim of the present study was to examine the lesions induced by Francisella tularensis in 50 cases of naturally infected seropositive European brown hares. Gross pathological examination revealed scant to numerous grayish-white foci with diameters of 0.1 to 1.0 cm in single organs (24 cases) or multiple organs (20 cases) in 44 of 50 cases (88%). These lesions proved to be areas of granulomatous inflammation, frequently encompassing necrosis. F tularensis antigen was detected with immunohistochemistry in 46 of 50 cases (92%), whereas F tularensis ssp holarctica was isolated by culture and identified by polymerase chain reaction from 35 of 50 cases (70%). Infection by the respiratory route is suggested by the presence of the tissue lesions in thoracic organs of 44 of 50 cases (88%). These results emphasize the importance of the European brown hare as a reservoir of tularemia.

Gastroduodenal artery pseudoaneurysm ruptured in the common bile duct.

A pseudoaneurysm of the gastroduodenal artery (GDA) is the rarest splanchnic artery aneurysm, comprising fewer than 10% of these lesions. Bleeding into the gastrointestinal tract is the most rapidly fatal complication of an arterial visceral pseudoaneurysm, affecting 4-10% of patients. We present an unusual case of a GDA pseudoaneurysm that ruptured in the common bile duct, and that was successfully treated by partial resection and hepatic artery reconstruction. The postoperative evolution was favourable and the CT performed six months later disclosed the absence of a vascular tumour.

Characterization of Francisella tularensis strains, comparing their carbon source utilization.

Thirteen Francisella tularensis strains were isolated from 22 seropositive brown hares (Lepus europaeus) originating from different parts of Hungary, and further two from a patas monkey (Erythrocebus patas) and vervet monkey (Chlorocebus aethiops). The isolates were identified as F. tularensis ssp. holarctica on the basis of culture, morphological and biochemical characteristics. The identification was verified by polymerase chain reaction and the sequencing of the partial 16S rRNA gene. Utilization of carbon sources of the 15 F. tularensis strains was characterized with the Biolog system. The system was able to identify the strains already after 4 h of incubation, not only after the standard 24 h. After the analysis and comparison of the metabolic profiles of our strains with the Biolog database, it was concluded that not all carbon sources indicated in the database were utilized by our isolates. The Biolog software fails to distinguish the highly virulent F. tularensis ssp. tularensis and the moderately virulent F. tularensis ssp. holarctica but the Biolog microplates can be manually read to differentiate the two subspecies based on glycerol source utilization. As all the studied strains were unable to use glycerol, they could be identified as F. tularensis ssp. holarctica. The dendrogram based on the metabolic relationship of the strains shows that the isolates are very similar to each other, which correlates with the conservative genetic character of F. tularensis ssp. holarctica.

Different models of training and certification in plastic surgery.

A varying period of training followed by examinations is the usual way to become a specialist in one of the many fields of Medicine. Plastic Surgery is one of the surgical fields that require good technical and cognitive skills. The best way to train and evaluate a candidate is hard to judge. The model of training and board examination varies, every country having its own method. This is a descriptive report presenting the ways of training residents in Plastic Surgery and then examining them in Romania, Israel, U.S.A., Germany and the Netherlands. Specific points regarding the structure and the format are addressed for all models and also for factors that might influence the objectivity of the examination. The authors bring their thoughts on these issues.

Simultaneous extra-anatomic bypass and abdominal "flag flap" for lower limb salvage in a patient with severe post-bypass anastomotic groin infection.

The incidence of prosthetic graft infection after bypass surgery ranges from 0.2 to 5%, depending on location, co-morbid diseases and host defense mechanisms. In spite of surgical treatment, the amputation rate can be up to 67%. Herein, we present our treatment strategy for a patient with severe Methicillin Resistant Staphylococcus Aureus infection and pseudo-aneurysm after a femoropopliteal bypass with a prosthetic graft. An extra-anatomic bypass without touching the previously operated groin area (aseptic time) was done at the beginning. Radical debridement (septic time) and simultaneous abdominal "flag flap" were performed in the same surgical procedure to save the lower limb.

Crop competitiveness influenced by seeding dates and top-dress nitrogen rates.

A competitive crop utilizes resources before they are available to the weeds. The essential steps of developing a competitive crop begin with good stand establishment. A vigorously growing crop is also important towards establishing a competitive stand. Components of establishing a good and vigorous crop stand include crop rotation, seedbed preparation, crop type and variety selection, seed quality and treatment, seeding rate (stand density), seeding date, fertilizer rate and placement, pest and disease control, etc. Failure to properly manage these components leads to poor germination, week seedlings with poor grows and vigor therefore promotes weed competition with the crop. Biomass production and density of weeds and winter wheat plants was studied in a seeding time and nitrogen application small-plot field trial. This trial was a perfect example of how the proper management practices help us to decrease weediness and increase competition of winter wheat. The trial included 3 planting date treatments (early, optimum and late) and 2 nitrogen rate treatments (56 kg N ha-1 and 110 kg N ha-1) in spring top-dressing application. The influence of treatments on the weed infestation and crop plant vs. weed competition was studied at beginning of steam extension (BBCH 32-33, two visible nodes on the steam) and after harvest on the stubble-field. The competitiveness of weeds and crop plants were evaluated by biomass production and also by nutrient content of plant samples. Biomass forming of weeds in wheat canopy was negligible compared to that of weeds, but it was strong on the stubble. Delayed planting Leaded to poorer wheat growth and better weed biomass production. The higher rate of nitrogen resuited in a less weediness on early and optimum time seeded plots, but the tendency was opposite in the late seeded treatment.

Patient satisfaction after removal of skin lesions.

BACKGROUND: Removal of skin lesions is one of the most common surgical procedures, with the number increasing progressively since the 1980s. OBJECTIVE: We tried to evaluate the satisfaction level of patients after removal of skin lesions and to identify the factors influencing it. STUDY DESIGN: The study group consisted of 138 patients who had skin lesions removed by shaving or primary excision and closure. They were evaluated 1 year after the procedure. Two questionnaires were completed independently by the patient and the surgeon. RESULTS: The main indication for the procedure was suspicion of malignancy, functional disturbance, or aesthetic reason. The satisfaction level (general and specific areas) for patients who had a malignant tumour removed was similar to those who had a benign tumour removed. Females were less satisfied than males (P = 0.05). Younger people were less satisfied with the aesthetic results (P = 0.007). Patients who had at least one significant side-effect were less satisfied than those who did not mention any side-effects (P = 0.038). The higher the level of patient satisfaction, the higher the level of surgeon satisfaction (P = 0.012). CONCLUSION: Skin lesion removal, although considered to be a minor procedure, leaves scars that sometimes disturb the patient. According to our study, the most prevalent population for dissatisfaction is females and young males.

A 17beta-derivative of allopregnanolone is a neurosteroid antagonist at a cerebellar subpopulation of GABA A receptors with nanomolar affinity.

BACKGROUND AND PURPOSE: High-affinity, subtype-selective antagonists of the neurosteroid binding sites of GABA(A) receptors are not available. We have characterized an allopregnanolone derivative as an antagonist of cerebellar GABA(A) receptors with nanomolar affinity. EXPERIMENTAL APPROACH: Receptor binding and electrophysiological methods were used for the allosteric modulation of cerebellar GABA(A) receptors by an allopregnanolone derivative, (20R)-17beta-(1-hydroxy-2,3-butadienyl)-5alpha-androstane-3alpha-ol (HBAO). GABA(A) receptors of rat cerebellar membranes were labelled with the chloride channel blocker [(3)H]ethynylbicycloorthobenzoate (EBOB). The ionophore function of GABA(A) receptors was studied by whole-cell patch clamp electrophysiology in cultured rat cerebellar granule and cortical cells. KEY RESULTS: Partial displacement of cerebellar [(3)H]EBOB binding by nanomolar HBAO was attenuated by 0.1 mM furosemide, an antagonist of alpha(6) and beta(2-3) subunit-containing GABA(A) receptors. Displacement curves of HBAO were reshaped by 30 nM GABA and shifted to the right. However, the micromolar potency of full displacement by allopregnanolone was not affected by 0.1 mM furosemide or 30 nM GABA. The nanomolar, but not the micromolar phase of displacement of [(3)H]EBOB binding by GABA was attenuated by 100 nM HBAO. Submicromolar HBAO did not affect [(3)H]EBOB binding to cortical and hippocampal GABA(A) receptors. HBAO up to 1 microM did not affect chloride currents elicited by 0.3-10 microM GABA, while it abolished potentiation by 1 microM allopregnanolone with nanomolar potency in cerebellar but not in cortical cells. Furosemide attenuated cerebellar inhibition by 100 nM HBAO. CONCLUSIONS AND IMPLICATIONS: HBAO is a selective antagonist of allopregnanolone, a major endogenous positive modulator via neurosteroid sites of cerebellar (probably alpha(6)beta(2-3)delta) GABA(A) receptors.