Epistatic effect of TLR-1, -6 and -10 polymorphisms on organic dust-mediated cytokine response.

Exposure to organic dust from agricultural environments is associated with inflammatory respiratory conditions. The putative causal agents in organic dust include viral, microbial and fungal components, which are recognized by the family of Toll-like receptors (TLRs) and drive host innate and adaptive responses. Our aim in this study was to determine whether responsiveness to organic dust among agricultural workers was dependent on polymorphisms in the TLR10-TLR1-TLR6 gene cluster. We stimulated whole blood from 509 agricultural workers with organic dust, triacyl lipopeptide N-palmitoyl-S-dipalmitoylglyceryl Cys-Ser-(Lys)4 (Pam3CSK4) and the diacyl-lipopeptide peptidoglycan. Several of the tagging polymorphisms and haplotypes conferred hyper-responsiveness to organic dust with an increase in interleukin-6 (IL-6; P<0.005), but not tumor necrosis factor-α (TNF-α), secretion. We conclude that genetic variation in the TLR10-TLR1-TLR6 gene cluster mediates responsiveness to organic dust, but indicates different signaling pathways for IL-6 and TNF-α. These studies provide new insight into the role of the TLR10-TLR1-TLR6 gene cluster and the innate immune response to organic dust.

Long-term (4 years) results of choroidal hemangioma treated with proton beam irradiation.

BACKGROUND: The aim of this retrospective study was to determine the efficacy of proton beam irradiation in choroidal hemangioma in a long-term follow-up. PATIENTS AND METHODS: A total dose of 20 Cobalt Gray equivalent (CGE) was administered to 50 eyes of 50 patients from September 1998 to September 2010. All treated patients presented with a symptomatic tumor. Nine patients were pre-treated by photodynamic therapy (PDT). Visual outcome, tumor regression, and complications resulting from radiation were investigated. RESULTS: The mean follow-up was 55.4 months (range 13-132). Tumor thickness decreased in all patients. Retinal re-attachment was achieved without evidence of tumor leakage. Visual acuity improved by two lines after one year in 43.4 % of patients and after two years in 36.8 % of patients. During the 55.4 months of long-term follow-up the visual acuity improved from 6/15 to 6/12 after proton therapy. Twenty-three patients (46.0 %) developed radiation retinopathy. According to the Finger classification of 2004, 21 patients (42.0 %) showed a stage 1 or 2 (functionally not relevant) retinopathy, and two patients (4.0 %) presented a stage 3 or 4 (functionally relevant) retinopathy. Further complications included sicca syndrome in nine cases, cataract formation in 10 cases, and radiation optic neuropathy in four cases. CONCLUSION: Proton therapy with 20 CGE is an efficient primary therapy in choroidal hemangioma and is very effective as a secondary treatment after PDT.

Long-term outcome for gastric marginal zone lymphoma treated with radiotherapy: a retrospective, multi-centre, International Extranodal Lymphoma Study Group study.

BACKGROUND: We evaluated the long-term results of radiotherapy for patients with gastric marginal zone lymphoma (GMZL). PATIENTS AND METHODS: We carried out a retrospective, multi-centre study of patients with low-grade GMZL treated by radiotherapy between 17 July 1981 and 25 March 2004. RESULTS: There were 102 eligible patients. Fifty-eight patients were previously untreated and 44 had recurrent/residual disease after prior treatment (HP eradication, chemotherapy and surgery in 35, 9 and 8 patients, respectively, and 7 had >1 prior therapy). Radiation fields included the stomach /involved nodes in 61 patients and whole abdomen in 41. The median radiotherapy dose to stomach was 40 Gy (range 26-46 Gy) in a median 22 fractions. With a median follow-up after radiotherapy of 7.9 years (range 0.3-24 years), 10- and 15-year freedom from treatment failure (FFTF) was 88% (95% CI 82%-95%). Risk factors for TF were a large-cell component (P = 0.036) and an exophytic growth pattern (P = 0.042). Radiotherapy field size, radiotherapy dose, and failure of prior therapy were not associated with inferior FFTF. Ten-year overall survival was 70% (95% CI 60%-82%). CONCLUSIONS: Radiotherapy achieves cure for the majority of patients with low-grade GMZL, including patients who have had prior therapy. Several features may predict a poorer outcome.

[Diagnosis of and therapy for choroidal melanoma]. / Diagnostik und Therapie choroidaler Melanome.

BACKGROUND: Prognosis evaluation of patients with choroidal and ciliary melanoma has experienced recent progress through tumour sampling and cytogenetic analysis of metastatic risk. By allocating tumor extension, height and linear basal diameter to defined TNM stages, an estimation of prognosis can also be made without invasive tissue sampling. METHODS: Therapeutic strategies of organ preserving irradiation using different sources have clearly come to the forefront. RESULTS: Due to microscopic haematogenous spreading of tumour cells prior to treatment, the metastatic risk following radiation of any form is not influenced in comparison to primary enucleation. CONCLUSION: However, metastatic disease still remains a fatal condition which currently may only be influenced by early detection and treatment of uveal melanomas.

Locally recurrent colorectal cancer: results of surgical therapy.

PURPOSE: Up to 20 % of colorectal cancer patients develop recurrent disease despite standardized surgical techniques and multimodal treatment strategies. Radical resection is the central component of curative therapy in these cases. The aim of this study was to evaluate treatment results in patients with locoregionally recurrent colorectal cancer. METHODS: From January 1995 to December 2007, surgery was performed for recurrent colorectal cancer in 82 patients who had undergone curative (R0) resection of their primary tumor. Assessment included patient, tumor and treatment characteristics, postoperative complications, and time without re-recurrence; recurrence-free and overall survival rates were calculated according to the Kaplan-Meier method. RESULTS: Resection was performed in 60 of the 82 patients (73 %), repeat R0 resection in 52 % (31/60). Patients had a postoperative morbidity of 39 % (31/82), a relaparotomy rate of 13 % (11/82), and a lethality of 7 % (6/82). Forty-eight percent of all surgically-treated patients received a permanent stoma. Re-recurrence was seen in 52 % (16/31). R0 resection was associated with a 5-year survival rate of 35 % (11/31). CONCLUSIONS: Extensive reinterventions often enable repeat R0 resection. Despite relevant morbidity, the lethality appears to be acceptable. Decisive for the prognosis is re-recurrence.

[Results of clinical use of the German version of the APHAB]. / Klinische Ergebnisse bei der Anwendung des APHAB (deutsche Version) in der Hörgeräteversorgung.

OBJECTIVE: Speech audiometry studies do not deliver structured testimony of patients as to the actual benefit of hearing aids based on individual daily life experiences. This deficiency can be resolved by applying structured inventory questionnaires. The APHAB (German version) is an evaluated inventory questionnaire consisting of six questions put to patients with hearing deficiencies with and without hearing aids in four different hearing situations. MATERIALS AND METHODS: We collected the APHAB data of 560 patients before and after fitting hearing aids. We also gathered personal data as to age, prior experience with hearing aids, duration of daily use of the hearing aid and degree of hearing loss. RESULTS: The average age of the patients was a little under 70 years, 84% had just received their first hearing aid, and 83% exhibited moderate or severe hearing loss. The APHAB results were classified in percentile and contingency tables. The latter allow one to determine conditional probabilities of the potential success of fitting a hearing aid to a new patient for each APHAB scale. CONCLUSIONS: The APHAB can be applied regularly to measure the benefit of fitting a hearing aid to a patient in particular in problematic hearing situations. By registering the personal view of the patients, it expands the scope of the standard methods (e.g., speech audiometry) so that the quality of diagnostics and therapy can be improved. It qualitatively records the success of hearing aid fitting, predicts potential problem areas and thereby may reduce the number of unused hearing aids.

Under-correction of preoperative varus alignment does not lead to a difference in in-vivo bone loading in 3D-SPECT/CT compared to neutral alignment.

BACKGROUND: The aim was to investigate the correlation of bone tracer uptake (BTU) in SPECT/CT and changes in coronal knee alignment after total knee arthroplasty (TKA). We questioned if undercorrection of preoperative varus alignment leads to a difference in BTU compared to neutral alignment. METHODS: Consecutive 66 patients who received SPECT/CT before and after TKA were retrospectively included. Adjusted mechanical alignment was the alignment target. The alignment of the knee was measured on 3D-CT by selecting standardized landmarks. Maximum (mean ± SD) and relative BTU (ratio to the reference) were recorded using a previously validated localization scheme (p < 0.05). RESULTS: In the native group, 20 knees were aligned (30.3%) in valgus (HKA > 181.5°), 12 (18.2%) in neutral (178.5°-181.5°) and 34 (51.5%) in varus (HKA < 178°). Overall TKA changed the alignment towards neutral. 48.5% remained in the same groups, whereas 50% of native valgus and 33% of varus knees changed to neutral after TKA. In native varus alignment mean BTU was significantly higher in some medial tibial and femoral regions (fem1ia (p = 0.010), fem1ip (p = 0.002), tib1a.mid (p = 0.005), tib1a.tray (p = 0.000), tib1p.tray (p = 0.000)); in native valgus alignment mean BTU was higher in the corresponding lateral tibial and femoral regions (fem2ip (p = 0.001), tib2a.tray (p = 0.011), tib2p.tray (p = 0.002)). After TKA, a significant decrease in femoral and tibial BTU (femoral preoperative BTU 1.64 +/-0.69; femoral postoperative BTU 0.95 +/-0.42; p = 0.000// tibial preoperative BTU 1.65 +/- 0.93; tibial postoperative BTU 1.16 +/- 0.48; p = 0.000) and an increase in patellar BTU was observed (p = 0.025). Native varus alignment correlated with a higher medial BTU decrease medially. Undercorrection of preoperative varus alignment showed no higher BTU after TKA. CONCLUSION: Preoperative varus alignment correlated with a higher decrease in BTU in specific femoral and tibial medial regions. Preoperative valgus alignment correlated with a higher decrease in the corresponding lateral regions. Undercorrection of preoperative varus alignment did not lead to higher bone loading reflected by BTU after TKA.

[Hearing quality with different cochlear implants]. / Qualität des Hörens und der Kommunikation mit unterschiedlichen Cochlea-Implantaten.

The rehabilitation of completely or profoundly deaf patients with a cochlear implant shows different results in their ability to communicate. These differences are certainly based upon the different kind and degree of the disease or damage leading to the loss of hearing. But as CI-systems are also different, an attempt was made to find out the CI-system offering the best chance for an optimal communication ability. Anonymously answered questionnaires of 45 and 193 patients in 2 series were statistically analysed. In both the 95% intervals of confidence for numbers of patients with 2 different CIs who could mainly communicate without additional optical or electronic help did not overlap. For Nucleus 62% and for MED-EL 83% of patients obtained a mainly free communication ability. The difference was statistically significant.

[The use of the German APHAB for quality control in hearing aid fitting in an ENT-office. Comparison of our results with the given US-norm]. / Die Verwendung des APHAB zur Messung der Hörgeräteversorgungsqualität in der HNO-Praxis.

OBJECTIVE: ISO 9001 recommends a customer survey both pre and post hearing aid fitting. A lot of different German questionnaires are in use, but most of them have not been investigated by a large number of patients. The APHAB is well evaluated in the US. We want to compare our APHAB (German) outcome with the US-norm given by the HARL, to be able to answer the question if the German-APHAB can be used for quality control in hearing aid fitting done in a German ENT-office. Furthermore we want to discuss some special aspects of the benefit of the APHAB in quality control of hearing aid fitting. MATERIAL AND METHODS: We collected the APHAB data of 224 patients in 9 ENT-offices. The scores were measured pre and post fitting. We compared APHAB mean score for EC-, RV-, BN-, and AV-subscale and performed a wider outlook by statistical methods. RESULTS: We tested the null-hypothesis: "There is no difference between the percentiles given by HARL and ours". All probabilities by using the Wilcoxon rank sum test are greater than 0.025, so we have to accept this with a p < 2.5%. By using the sign test we got a probability of a positive benefit for hearing aid fitting of about 75-78% in the EC-, BN-, RV- and 28% in the AV-subscale (confidence interval 95%). CONCLUSIONS: The trial shows, that we can well use the German-APHAB for quality control in hearing aid fitting done in an ENT-office. Patients fitted in a German ENT-office score the same as patients fitted by US-audiologists. We will continue using the APHAB forms, analyse the scoring and use it for technical adjustments to increase the coaching for negative scoring patients.

[Treatment modalities for conjunctival melanoma]. / Therapeutische Optionen in der Behandlung des malignen Melanoms der Bindehaut.

BACKGROUND: Because of high local recurrence rates after excision of conjunctival melanoma adjuvant local chemotherapy employing mitomycin C (MMC) or irradiation is recommended. Brachytherapy is possible with ruthenium-106-plaques ((106)Ru) or with the strontium-90-plaques ((90)Sr). PATIENTS AND METHODS: Fifty-six patients received an excision and adjuvant radiotherapy of conjunctival melanoma between 1992 and 2007. The mean follow-up was 42 months (12 - 151 months). Mean age was 62 (28- 86) years. As an adjuvant radiotherapy 15 patients received X-ray irradiation, 12 patients received (106)Ru-brachytherapy, 4 patients received proton beam therapy and 16 patients with conjunctival melanoma were treated with adjuvant strontium-90 brachytherapy after tumour excision. Four patients received proton beam irradiation and in 13 patients an exenteratio was performed. RESULTS: Twelve patients (21 %) developed tumour recurrences in or adjacent to the irradiated area. Thirteen patients (22 %) showed a recurrence distant from the primary site. Ten patients (18 %) developed systemic metastasis during follow-up. Seven patients (46 %) had no recurrence during the follow-up. Three patients (20 %) had a recurrence in the treated or adjacent areas. Eight patients (53 %) developed new tumours in non-treated areas. CONCLUSIONS: Adjuvant radiotherapy allows an acceptable local tumour control rate after excision of conjunctival melanoma. No obvious differences regarding tumour control or systemic metastasis could be seen between the different modes of radiotherapy used.

Herd-level prevalence and incidence of porcine epidemic diarrhoea virus (PEDV) and porcine deltacoronavirus (PDCoV) in swine herds in Ontario, Canada.

Porcine epidemic diarrhoea virus (PEDV) and porcine deltacoronavirus (PDCoV) were first identified in Canada in 2014. Surveillance efforts have been instrumental in controlling both diseases. In this study, we provide an overview of surveillance components for the two diseases in Ontario (Canada), as well as PEDV and PDCoV incidence and prevalence measures. Swine herds located in the Province of Ontario, of any type, whose owners agreed to participate in a voluntary industry-led disease control programme (DCP) and with associated diagnostic or epidemiological information about the two swine coronaviruses, were eligible to be included for calculation of disease frequency at the provincial level. PEDV and PDCoV data stored in the industry DCP database were imported into the R statistical software and analysed to produce weekly frequency of incidence counts and prevalence counts, in addition to yearly herd-level incidence risk and prevalence between 2014 and 2016. The yearly herd-level incidence risk of PEDV, based on industry data, was 13.5%, 3.0% and 1.4% (95% CI: 11.1-16.2, 2.0-4.2, 0.8-2.3), while the yearly herd-level incidence risk of PDCoV was 1.1%, 0.3%, and 0.1% (95% CI: 0.5-2.2, 0.1-0.9, 0.0-0.5), for 2014, 2015 and 2016, respectively. Herd-level prevalence estimates for PEDV in the last week of 2014, 2015 and 2016 were 4.4%, 2.3% and 1.4%, respectively (95% CI: 3.1-6.0, 1.5-3.3, 0.8-2.2), while herd-level prevalence estimates for PDCoV in the last week of 2014, 2015 and 2016 were 0.5%, 0.2% and 0.2%, respectively (95% CI: 0.1-1.2, 0.0-0.6, 0.0-0.6). Collectively, our results point to low and decreasing incidence risk and prevalence for PEDV and PDCoV in Ontario, making both diseases possible candidates for disease elimination at the provincial level.

Development of a tele-stethoscope and its application in pediatric cardiology.

Over the years, many attempts have been made to develop special stethoscopes for the teaching of auscultation. The objective of this article is to report on the experience with the development and implementation of an electronic stethoscope and a virtual library of cardiac sounds. There were four stages to this project: (1) the building of the prototype to acquire, filter and amplify the cardiac sounds, (2) the development of a software program to record, reproduce and visualize them, (3) the testing of the prototype in a clinical scenario, and (4) the development of an internet site, to store and display the sounds collected. The first two stages are now complete. The prototype underwent an initial evaluation in a clinical scenario within the Unit and during virtual out-patient clinical sessions. One hundred auscultations were recorded during these tests. They were reviewed and discussed on-line by a panel of experience cardiologists during the sessions. Although the sounds were considered "satisfactory" for diagnostic purposes by the cardiology team, they identified some qualitative differences in the electronic recorded auscultations, such as a higher pitch of the recorded sounds. Prospective clinical studies are now being conducted to further evaluate the interference of the electronic device in the physicians' capability to diagnose different cardiac conditions. An internet site (www.caduceusvirtual.com.br/ auscultaped) was developed to host these cardiac auscultations. It is set as a library of cardiac sounds, catalogued by pathologies and already contains examples from auscultations of the majority of common congenital heart lesions, such as septal defects and valvar lesions.

Cleaning of first mirrors in ITER by means of radio frequency discharges.

First mirrors of optical diagnostics in ITER are subject to charge exchange fluxes of Be, W, and potentially other elements. This may degrade the optical performance significantly via erosion or deposition. In order to restore reflectivity, cleaning by applying radio frequency (RF) power to the mirror itself and thus creating a discharge in front of the mirror will be used. The plasma generated in front of the mirror surface sputters off deposition, restoring its reflectivity. Although the functionality of such a mirror cleaning technique is proven in laboratory experiments, the technical implementation in ITER revealed obstacles which needs to be overcome: Since the discharge as an RF load in general is not very well matched to the power generator and transmission line, power reflections will occur leading to a thermal load of the cable. Its implementation for ITER requires additional R&D. This includes the design of mirrors as RF electrodes, as well as feeders and matching networks inside the vacuum vessel. Mitigation solutions will be evaluated and discussed. Furthermore, technical obstacles (i.e., cooling water pipes for the mirrors) need to be solved. Since cooling water lines are usually on ground potential at the feed through of the vacuum vessel, a solution to decouple the ground potential from the mirror would be a major simplification. Such a solution will be presented.

Contribution of human papilloma virus to the incidence of squamous cell carcinoma of the head and neck in a European population with high smoking prevalence.

BACKGROUND: Increases in incidence of oropharyngeal squamous cell carcinoma (OPSCC) in countries with falling tobacco use have been attributed to a growing role of human papilloma virus (HPV) in the carcinogenesis. Trends of HPV prevalence in populations with persistently high portions of smokers are poorly characterised. PATIENTS AND METHODS: Registry data from East Germany were used to determine incidence trends between 1998 and 2011. Data from patients treated at the Charité University Medicine Berlin between 2004 and 2013 (cohort 1, N=436) were used for estimation of trends in HPV prevalence, smoking and survival. HPV prevalence was prospectively confirmed in cohort 2 (N=213) comprising all primary HNSCC cases at the Charité in 2013. RESULTS: Between 1998 and 2011 incidence of both OPSCC and non-OPSCC increased. An increase in HPV prevalence (% of HPV+ cases in 2004-2006 versus 2012-2013: 27% versus 59%, P=0.0004) accompanied by a moderate decrease in the portion of current smokers was observed in OPSCC but not in non-OPSCC. The change in disease epidemiology in OPSCC was associated with significant improvement in overall survival. Increased HPV prevalence in OPSCC (48%) compared to non-OPSCC (11%) was confirmed in cohort 2. CONCLUSIONS: Despite clear differences to the United States in terms of tobacco use, the increase in OPSCC incidence in a European population was also mainly attributed to HPV, and the HPV status significantly affected prognosis. For clinical trial design it is important to consider the large group of smokers within HPV-induced OPSCC.

Diagnosis of Meckel's diverticulum by radioisotope scanning.

The clinical illness observed in a 5-month-old infant with Meckel's diverticulum is described. A sodium pertechnetate radioisotope scan was employed to confirm the clinical impression. The technical procedure, evaluation, and importance of the radioisotope study is discussed.

Variation in reference cells for DNA analysis of paraffin-embedded tissue.

Selection of the diploid reference cells used in flow cytometric DNA analysis of paraffin-embedded tissue is inconsistent in the literature. To determine which types of cells were most suitable for use as reference cells, benign paraffin-embedded tissue was evaluated from nine randomly selected autopsies. Benign kidney, lymph node, gastrointestinal mucosa, laryngeal mucosa, bronchial mucosa, bladder mucosa, pancreas, and, when available, prostate tissue were studied. Ten paraffin-embedded surgical specimens also were studied. In the autopsy specimens, great variability in the mean peak channels was noted on intrapatient evaluation and even more variability was present when comparing similar organs (especially lymph nodes) from different patients. Similar results were obtained using lymph nodes from surgical specimens. It is concluded that the most suitable diploid reference cells for DNA analysis of paraffin-embedded tissue are the benign cells present in the paraffin tumor block that have been processed in the same way as the tumor cells.

The effects of the atypical antipsychotic amperozide on vacuous jaw movements in rats: a novel dose response profile.

Classic neuroleptic drugs produce a syndrome of vacuous jaw movements in rats, and this syndrome has been offered as an animal model of early onset extrapyramidal side effects. The atypical antipsychotics do not produce elevations in vacuous jaw movements, or do so only at very high doses. The purpose of the present study was to determine the impact of the putative antipsychotic, amperozide, on vacuous jaw movements in rats. Groups of rats received daily injections of haloperidol (0.2, 0.4, or 0.8 mg/kg), clozapine (2.0, 4.0, 8.0 mg/kg), amperozide (2.0, 4.0, 8.0 mg/kg) or vehicle for 4 weeks. Once per week, rats were observed for the presence of vacuous jaw movements. Haloperidol increased vacuous jaw movements with increasing doses. Clozapine only produced elevations in vacuous jaw movements at the highest dose. In contrast, increasing doses of amperozide resulted in decreasing vacuous jaw movements for this portion of the dose-response curve. This is the first report of the effect of amperozide on vacuous jaw movements and results are discussed in terms of a potentially unique behavioral profile with respect to this behavior.

Fatality due to intravenous diltiazem for acute ventricular rate control.

Progressive, sustained bradycardia resulting in asystole and subsequent death is reported in a 70-year-old woman with hyperkalemia and suspected digoxin toxicity following a 0.25 mg/kg intravenous diltiazem dose for treatment of atrial fibrillation with a rapid ventricular response. The possible pharmacodynamic and pharmacokinetic interactions between diltiazem, digoxin, and an elevated plasma potassium concentration are discussed and related to the outcome of the case. The routine practice of concomitant administration of diltiazem for rapid ventricular rate control and digoxin for long-term control may be dangerous in a subset of patients.

Ruminal degradation of switchgrass, big bluestem, and smooth bromegrass leaf proteins.

Two in situ protein disappearance experiments were conducted to determine disappearance rates of leaf protein fractions and characterize individual leaf protein fractions that escaped ruminal degradation. Fresh leaf blades of two warm-season grasses, switchgrass (Panicum virgatum L.) and big bluestem (Andropogon gerardii Vitman), and one cool-season grass, smooth bromegrass (Bromus inermis Leyss.), were included in Exp. 1. Only warm-season grasses were used in Exp. 2. Leaves were harvested from greenhouse-grown plants, placed in polyester bags, and incubated up to 48 h in situ in three ruminally fistulated steers fed diets of warm-season grass hay. The rate of protein disappearance for switchgrass (.037 h-1) was slower (P < .10) than that for big bluestem (.110 h-1). Big bluestem and smooth bromegrass (.169 h-1) disappeared at similar rates, whereas switchgrass disappeared more slowly (P < .05) than smooth bromegrass in Exp. 1. Rates of protein disappearance in Exp. 2 were similar for switchgrass (.112 h-1) and big bluestem (.116 h-1). Major protein fractions that resisted ruminal degradation in both experiments, detected using SDS-PAGE, were at approximate molecular weights of 56, 26, and 24 kDa. For switchgrass and big bluestem, total protein and individual protein fractions were generally at higher concentrations and present for longer periods of time than for smooth bromegrass. This suggests that a mechanism may exist in C4 species that allows certain protein fractions to remain undegraded for longer periods compared with smooth bromegrass.

Radionuclide and radiographic demonstration of condensing osteitis of the clavicle.

Radionuclide and radiographic images of a case of condensing osteitis of the clavicle are presented. The clinical and radiographic features are discussed along with a differential diagnosis of sclerotic lesions of the clavicle.