The retinal basis of vision in chicken.

The Avian retina is far less known than that of mammals such as mouse and macaque, and detailed study is overdue. The chicken (Gallus gallus) has potential as a model, in part because research can build on developmental studies of the eye and nervous system. One can expect differences between bird and mammal retinas simply because whereas most mammals have three types of visual photoreceptor birds normally have six. Spectral pathways and colour vision are of particular interest, because filtering by oil droplets narrows cone spectral sensitivities and birds are probably tetrachromatic. The number of receptor inputs is reflected in the retinal circuitry. The chicken probably has four types of horizontal cell, there are at least 11 types of bipolar cell, often with bi- or tri-stratified axon terminals, and there is a high density of ganglion cells, which make complex connections in the inner plexiform layer. In addition, there is likely to be retinal specialisation, for example chicken photoreceptors and ganglion cells have separate peaks of cell density in the central and dorsal retina, which probably serve different types of behaviour.

Therapies with CCL25 require controlled release via microparticles to avoid strong inflammatory reactions.

BACKGROUND: Chemokine therapy with C-C motif chemokine ligand 25 (CCL25) is currently under investigation as a promising approach to treat articular cartilage degeneration. We developed a delayed release mechanism based on Poly (lactic-co-glycolic acid) (PLGA) microparticle encapsulation for intraarticular injections to ensure prolonged release of therapeutic dosages. However, CCL25 plays an important role in immune cell regulation and inflammatory processes like T-cell homing and chronic tissue inflammation. Therefore, the potential of CCL25 to activate immune cells must be assessed more thoroughly before further translation into clinical practice. The aim of this study was to evaluate the reaction of different immune cell subsets upon stimulation with different dosages of CCL25 in comparison to CCL25 released from PLGA particles. RESULTS: Immune cell subsets were treated for up to 5 days with CCL25 and subsequently analyzed regarding their cytokine secretion, surface marker expression, polarization, and migratory behavior. The CCL25 receptor C-C chemokine receptor type 9 (CCR9) was expressed to a different extent on all immune cell subsets. Direct stimulation of peripheral blood mononuclear cells (PBMCs) with high dosages of CCL25 resulted in strong increases in the secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-1ß (IL-1ß), tumor-necrosis-factor-α (TNF-α) and interferon-γ (IFN-γ), upregulation of human leukocyte antigen-DR (HLA-DR) on monocytes and CD4+ T-cells, as well as immune cell migration along a CCL25 gradient. Immune cell stimulation with the supernatants from CCL25 loaded PLGA microparticles caused moderate increases in MCP-1, IL-8, and IL-1ß levels, but no changes in surface marker expression or migration. Both CCL25-loaded and unloaded PLGA microparticles induced an increase in IL-8 and MCP-1 release in PBMCs and macrophages, and a slight shift of the surface marker profile towards the direction of M2-macrophage polarization. CONCLUSIONS: While supernatants of CCL25 loaded PLGA microparticles did not provoke strong inflammatory reactions, direct stimulation with CCL25 shows the critical potential to induce global inflammatory activation of human leukocytes at certain concentrations. These findings underline the importance of a safe and reliable release system in a therapeutic setup. Failure of the delivery system could result in strong local and systemic inflammatory reactions that could potentially negate the benefits of chemokine therapy.

High glucose exposure promotes proliferation and in vivo network formation of adipose-tissue-derived microvascular fragments.

High glucose concentrations have been shown to activate endothelial cells and promote angiogenesis. In the present study, it was investigated whether high glucose concentrations could improve the vascularisation capacity of adipose-tissue-derived microvascular fragments (ad-MVF). Ad-MVF were isolated from the epididymal fat pads of donor mice and cultivated for 24 h in University of Wisconsin (UW) solution supplemented with vehicle or 30 mM glucose. Protein expression, morphology, viability and proliferation of the cultivated ad-MVF were analysed by means of proteome profiler mouse angiogenesis array, scanning electron microscopy and immunohistochemistry. Additional cultivated ad-MVF were seeded on to collagen-glycosaminoglycan scaffolds to study their in vivo vascularisation capacity in the dorsal skinfold chamber model by intravital fluorescence microscopy, histology and immunohistochemistry. In vitro, high glucose exposure changed the protein expression pattern of ad-MVF with endoglin, interleukin (IL)-1ß and monocyte chemoattractant protein (MCP)-1 as the most up-regulated pro-angiogenic factors. Moreover, high glucose exposure induced the formation of nanopores in the ad-MVF wall. In addition, ad-MVF contained significantly larger numbers of proliferating endothelial and perivascular cells while exhibiting a comparable number of apoptotic cells when compared to vehicle-treated controls. In vivo, scaffolds seeded with high-glucose-exposed ad-MVF exhibited an improved vascularisation and tissue incorporation. These findings demonstrated that the exposure of cultivated ad-MVF to high glucose concentrations is a promising approach to improve their in vivo performance as vascularisation units for tissue engineering and regenerative medicine.

[Identification of Control Hospitals for the Implementation of the Nationwide and Standardized Evaluation of Model Projects According to § 64b SGB V: Analysis of Data from Structured Quality Reports]. / Auswahl geeigneter Kontrollkliniken für die Durchführung der bundesweiten und einheitlichen Evaluation von Modellvorhaben nach § 64b SGB V. Analyse von Daten der Strukturierten Qualitätsberichte.

BACKGROUND: Health care needs of mentally ill patients make special demands on cross-sectoral health care structures. § 64b SGB V enables care of mentally ill patients through model projects that are multi-professional, work across treatment periods and sectors and implement new forms of financing. These model projects in their hospitals (case hospitals) need to be evaluated and compared with standard treatment methods. OBJECTIVES: The aim of this analysis is to identify matching hospitals according to a priori defined criteria for the establishment of a control group (control hospitals) using secondary data. MATERIALS AND METHODS: A systematic analysis was conducted based on structured quality reports according to §+137 SGB V and matched data from the Federal Institute for Research on Building, Urban Affairs and Spatial Development (BBSR). Based on a priori defined knock-out criteria, criteria based on patients (weighting 50%), structural features of hospitals (25%) and environmental factors (25%), a weighted similarity score was calculated for each of the 13 case hospitals, which could reach the maximum of 100 points (perfect match). RESULTS: 10 control hospitals per case hospital were identified according to the weighted similarity score. The median of the total deviation of potential control hospitals from the case hospitals was 34.3 (range: 17.6-66.7). The median of the 10 selected control hospitals per case hospital was 30.9 (range: 17.6-40.8). DISCUSSION: The defined algorithm could be used to identify similar control hospitals. The method using the mentioned databases and derivation of specific criteria of structural similarity are generally suitable in controlled designs for the evaluation of complex interventions based on routine data.

Phase transitions in huddling emperor penguins.

Emperor penguins (Aptenodytes forsteri) are highly adapted to the harsh conditions of the Antarctic winter: they are able to fast for up to 134 days during breeding. To conserve energy, emperor penguins form tight groups (huddles), which is key for their reproductive success. The effect of different meteorological factors on the huddling behaviour, however, is not well understood. Using time-lapse image recordings of an emperor penguin colony, we show that huddling can be described as a phase transition from a fluid to a solid state. We use the colony density as order parameter, and an apparent temperature that is perceived by the penguins as the thermodynamic variable. We approximate the apparent temperature as a linear combination of four meteorological parameters: ambient temperature, wind speed, global radiation and relative humidity. We find a wind chill factor of -2.9 °C/(ms -1), a humidity chill factor of -0.5°C/% rel. humidity, and a solar radiation heating factor of 0.3 °C//(Wm 2). In the absence of wind, humidity and solar radiation, the phase transition temperature (50% huddling probability) is -48.2°C for the investigated time period (May 2014). We propose that higher phase transition temperatures indicate a shrinking thermal insulation and thus can serve as a proxy for lower energy reserves of the colony, integrating pre-breeding foraging success at sea and energy expenditure at land due to environmental conditions. As current global change is predicted to have strong detrimental effects on emperor penguins within the next decades, our approach may thus contribute towards an urgently needed long-term monitoring system for assessing colony health.

Frequency and Distribution of Tuberculosis Resistance-Associated Mutations between Mumbai, Moldova, and Eastern Cape.

Molecular diagnostic assays, with their ability to rapidly detect resistance-associated mutations in bacterial genes, are promising technologies to control the spread of drug-resistant tuberculosis (DR-TB). Sequencing assays provide detailed information for specific gene regions and can help diagnostic assay developers prioritize mutations for inclusion in their assays. We performed pyrosequencing of seven Mycobacterium tuberculosis gene regions (katG, inhA, ahpC, rpoB, gyrA, rrs, and eis) for 1,128 clinical specimens from India, Moldova, and South Africa. We determined the frequencies of each mutation among drug-resistant and -susceptible specimens based on phenotypic drug susceptibility testing results and examined mutation distributions by country. The most common mutation among isoniazid-resistant (INH(r)) specimens was the katG 315ACC mutation (87%). However, in the Eastern Cape, INH(r) specimens had a lower frequency of katG mutations (44%) and higher frequencies of inhA (47%) and ahpC (10%) promoter mutations. The most common mutation among rifampin-resistant (RIF(r)) specimens was the rpoB 531TTG mutation (80%). The mutation was common in RIF(r) specimens in Mumbai (83%) and Moldova (84%) but not the Eastern Cape (17%), where the 516GTC mutation appeared more frequently (57%). The most common mutation among fluoroquinolone-resistant specimens was the gyrA 94GGC mutation (44%). The rrs 1401G mutation was found in 84%, 84%, and 50% of amikacin-resistant, capreomycin-resistant, and kanamycin (KAN)-resistant (KAN(r)) specimens, respectively. The eis promoter mutation -12T was found in 26% of KAN(r) and 4% of KAN-susceptible (KAN(s)) specimens. Inclusion of the ahpC and eis promoter gene regions was critical for optimal test sensitivity for the detection of INH resistance in the Eastern Cape and KAN resistance in Moldova. (This study has been registered at ClinicalTrials.gov under registration number NCT02170441.).

The determination of the radical power - an in vitro test for the evaluation of cosmetic products.

OBJECTIVE: Cosmetic formulations are influenced by environmental impacts and ageing, resulting in rancidity and change of colour and structure. These changes are caused by free radicals (FRs). The sensitivity of cosmetics generating FRs is a metric for its quality and should be determined. METHODS: Electron spin resonance spectroscopy in combination with UV irradiation tested cosmetics such as creams, milks, lotions and fragrances. The probes were directly measured without expensive preparation. RESULTS: Nine formulations are tested for its radical generation and ranked corresponding to the radical power. The transformation of the FR properties of three formulations to skin is measured by the radical skin status factor (RSF) method. It shows that the higher the radical power (RP) is, the lower the radical status RSF of skin will be. CONCLUSION: The knowledge of the sensitivity of cosmetics to generate FRs is necessary for its stabilization and prevention of potential damages to skin. It is a new way in development of cosmetics which has to be considered.

Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12.

BACKGROUND: Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months. PATIENTS AND METHODS: Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points. RESULTS: After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. CONCLUSION: These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term. CLINICALTRIALSGOV: NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).

[Implantable hemodynamic monitoring devices]. / Implantierbare hämodynamische Monitorsysteme.

Heart failure is one of the most frequent diagnoses in hospital admissions in Germany. In the majority of these admissions acute decompensation of an already existing chronic heart failure is responsible. New mostly wireless and remote strategies for monitoring, titration, adaptation and optimization are the focus for improvement of the treatment of heart failure patients and the poor prognosis. The implantation of hemodynamic monitoring devices follows the hypothesis that significant changes in hemodynamic parameters occur before the occurrence of acute decompensation requiring readmission. Three different hemodynamic monitoring devices have so far been investigated in clinical trials employing right ventricular pressure, left atrial pressure and pulmonary artery pressure monitoring. Only one of these systems, the CardioMENS™ HF monitoring system, demonstrated a significant reduction of hospitalization due to heart failure over 6 months in the CHAMPION trial. The systematic adaptation of medication in the CHAMPION trial significantly differed from the usual care of the control arm over 6 months. This direct day to day management of diuretics is currently under intensive investigation; however, further studies demonstrating a positive effect on mortality are needed before translation of this approach into guidelines. Without this evidence a further implementation of pressure monitoring into currently used devices and justification of the substantial technical and personnel demands are not warranted.

Bevacizumab treatment in malignant meningioma with additional radiation necrosis. An MRI diffusion and perfusion case study.

BACKGROUND AND PURPOSE: Recently two retrospective cohort studies report efficacy of bevacizumab in patients with recurrent atypical and anaplastic meningioma. Another successful therapeutic option of bevacizumab seems to be treatment of cerebral radiation necrosis. However, the antiangiogenic effects in MRI diffusion and perfusion in meningiomas have not been previously described in detail. The objective of this research was to evaluate the clinical and MR imaging effects of bevacizumab in a malignant meningioma patient harboring additional cerebral radiation necrosis. CASE PRESENTATION: We report the case of an 80-year-old woman who underwent bevacizumab therapy (5 mg/kg every 2 weeks for 2 months) for treatment of a symptomatic radiation necrosis in malignant meningiomatosis of World Health Organization (WHO) grade III. The patient was closely monitored with MRI including diffusion and perfusion studies. Upon bevacizumab therapy, the clinical situation was well stabilized over a period of 4 months until the patient unfortunately died due to pneumonia/septicemia probably unrelated to bevacizumab therapy. Consecutive MRI demonstrated 4 important aspects: (1) considerable decrease of the contrast medium (CM)-enhanced radiation necrosis, (2) mixed response with respect to the meningiomatosis with stable and predominantly growing tumor lesions, (3) a new diffusion-weighted imaging (DWI) lesion in a CM-enhanced tumor as described in gliomas, which we did not interpret as a response to bevacizumab therapy, and (4) new thrombembolic infarcts, which are a known side-effect of bevacizumab treatment. CONCLUSION: Bevacizumab is effective in the treatment of radiation necrosis. We could not confirm the potential antitumor effect of bevacizumab in this patient. However, we could describe several new radiographic effects of bevacizumab therapy in malignant meningioma.

Impact of body mass index on estradiol depletion by aromatase inhibitors in postmenopausal women with early breast cancer.

BACKGROUND: Body mass index (BMI) has an impact on survival outcome in patients treated with aromatase inhibitors (AIs). Obesity is associated with an increased body aromatisation and may be a cause of insufficient estradiol depletion. METHODS: Sixty-eight postmenopausal oestrogen receptor-positive patients with early breast cancer were prospectively included in this study. Follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were analysed immediately in the clinical routine lab and in a dedicated central lab before (T1) and 3 months after start with aromatase inhibitors (T2). RESULTS: A total of 40 patients were normal or overweight (non-obese: BMI 18.5-29.9 kg m(-2)) and 28 were obese (BMI ≥ 30 kg m(-2)). Aromatase inhibitors significantly suppressed estradiol serum levels (T1: 19.5 pg ml(-1), T2: 10.5 pg ml(-1), P<0.01) and increased FSH serum levels (T1: 70.2 mIU ml(-1), T2: 75.7 mIU ml(-1), P<0.05). However, after 3 months of AI treatment, estradiol levels of obese patients were nonsignificantly higher compared with non-obese patients (12.5 pg ml(-1) vs 9.0 pg ml(-1), P=0.1). This difference was reflected by significantly lower FSH serum levels in obese compared with non-obese patients (65.5 mIU ml(-1) vs 84.6 mIU ml(-1), P<0.01). The significant effects of BMI on FSH serum levels could be detected both in the routine as well as in the dedicated central lab. CONCLUSION: Aromatase inhibitors are less efficient at suppressing estradiol serum levels in obese when compared with non-obese women.

The predictive impact of body mass index on the efficacy of extended adjuvant endocrine treatment with anastrozole in postmenopausal patients with breast cancer: an analysis of the randomised ABCSG-6a trial.

BACKGROUND: We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment. METHODS: The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety. RESULTS: In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02) and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P=0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment (P=0.07). CONCLUSION: Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer.

Efficacy of tamoxifen ± aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial.

BACKGROUND: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial. METHODS: ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5-24.9 kg m(-)(2)), overweight (BMI=25-29.9 kg m(-)(2)), and obese (30 kg m(-)(2)) according to WHO criteria. RESULTS: Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients. CONCLUSION: BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen.

A 45-year-old female with hypokalemic rhabdomyolysis due to VIP-producing composite pheochromocytoma.

The watery diarrhea, hypokalemia and achlorhydria (WHDA) syndrome due to vasoactive intestinal polypeptide (VIP)-producing extra-pancreatic tumors is rare. We report on a 45-year-old woman who suffered from persistent secretory diarrhea for six years and who was admitted to hospital with complaints of muscular weakness and myalgia. Biochemical testing revealed pronounced rhabdomyolysis due to severe hypokalemia. Gastrointestinal evaluation of long-standing diarrhea including endoscopy of the upper and lower gastrointestinal tract and the small intestine did not show any pathologies. An abdominal computed tomography scan revealed a mass of 4 × 5 cm in the left adrenal gland demonstrating a strong uptake in the 123I-labelled metaiodobenzylguanidine scintigraphy. Plasma levels of chromogranin A, calcitonin, parathormone, basal renin and most prominently VIP were increased in line with a increased 24 hour urinary secretion of noradrenaline, dopamine, normetanephrine and vanillymandelic acid. A WDHA (watery diarrhea, hypokalaemia, achlorhydria) syndrome with hypokalemic rhabdomyolysis due to a VIP-producing adrenal tumor was diagnosed that was removed surgically. The histological evaluation demonstrated a composite pheochromocytoma. Diarrhea stopped immediately after surgery together with a normalization of laboratory parameters. In conclusion, this case report focuses on the rare clinical presentation of secretory diarrhea and electrolyte disturbances in combination with hypokalemic rhabdomyolysis which was caused by a VIP-producing composite pheochromocytoma.

Contributions of GeneXpert® to TB diagnosis in Myanmar.

BACKGROUND: Xpert® MTB/RIF, a rapid, molecular TB diagnostic assay, can detect Mycobacterium tuberculosis and rifampin resistance directly from clinical sputum samples in <2 h with high sensitivity and specificity. The added diagnostic value of Xpert over smear microscopy at a national level in Myanmar has not been previously reported.METHODS: We evaluated 339,358 Xpert and demographic records captured from January 2015 to December 2018 as part of the Myanmar National TB Program Data Utilization and Connectivity Project to examine the additional diagnostic yield of Xpert relative to smear for the detection of M. tuberculosis for TB diagnosis in Myanmar, with a focus on people living with HIV (PLHIV) and sample type.RESULTS: Use of Xpert increased TB case detection by 40% compared to smear microscopy results. Among PLHIV, use of Xpert increased TB case detection by almost 100% compared to smear microscopy results.CONCLUSION: Xpert testing identified more patients with TB than smear microscopy alone, particularly in cohorts with significant proportions of PLHIV. The use of Xpert as a screening tool in countries with a high burden of TB could lead to significantly increased diagnosis of TB at a regional and national level.

Vaginal estriol to overcome side-effects of aromatase inhibitors in breast cancer patients.

OBJECTIVE: Aromatase inhibitors are essential as endocrine treatment for hormone receptor-positive postmenopausal breast cancer patients. Menopausal symptoms are often aggravated during endocrine treatment. We investigated whether vaginal estriol is a safe therapeutic option to overcome the urogenital side-effects of aromatase inhibitors. Serum hormone levels were used as the surrogate parameter for safety. METHODS: Fasting serum hormone levels of ten postmenopausal breast cancer patients receiving aromatase inhibitors were prospectively measured by electro-chemiluminescence immunoassays and gas chromatography/mass spectrometry before and 2 weeks after daily application of 0.5 mg vaginal estriol (Ovestin® ovula), respectively. RESULTS: Two weeks of daily vaginal estriol treatment did not change serum estradiol or estriol levels. However, significant decreases in levels of serum follicle stimulating hormone (p = 0.01) and luteinizing hormone (p = 0.02) were observed. Five out of six breast cancer patients noticed an improvement in vaginal dryness and/or dyspareunia. CONCLUSIONS: The significant decline in gonadotropin levels, indicating systemic effects, has to be kept in mind when offering vaginal estriol to breast cancer patients receiving an aromatase inhibitor.

Factors influencing the identification rate of the sentinel node in breast cancer.

Sentinel node biopsy is a widely accepted alternative to primary axillary lymph node dissection for ipsilateral nodal assessment in breast cancer. We have performed a retrospective chart review in 713 consecutive patients with primary, operable breast cancer who underwent sentinel node biopsy in order to identify factors that determine the sentinel node identification rate. Chi-squared test, univariate and multivariate analyses were used to evaluate the influence of different factors on the sentinel identification rate. Among the factors investigated, tumour size was correlated with sentinel lymph nodes detection rates (multiple logistic regression, P= 0.002). In addition, the patient's age showed to be a significant influencing factor (multiple logistic regression, P= 0.006). Body mass index and grade only exhibited a significant correlation with the identification rate in the univariate (P= 0.041, P= 0.025), but not in the multivariate analysis (P= not significant). All associations were found to be independent of the site of injection. Interestingly, surgeons with intermediate expertise (11-20 prior dissections) had the highest detection rates (P= 0.004). We conclude that sentinel identification rates are higher in larger tumours and in younger patients, independent of the injection site. Surgical experience in sentinel node dissection is not linearly correlated with higher identification rates.

The effect of sodium thiosulfate on the recovery of Mycobacterium chimaera from heater-cooler unit water samples.

BACKGROUND: Heater-cooler units (HCUs) have been implicated in the recent global outbreak of invasive Mycobacterium chimaera infection among patients following cardiothoracic surgery. Because infected patients tend to remain asymptomatic for extended periods, detection of M. chimaera from HCUs in real time is essential to halting the ongoing M. chimaera HCU-associated outbreak. Sample collection protocols to evaluate the presence of M. chimaera offer conflicting recommendations regarding the addition of sodium thiosulfate (NaT) during the collection process. AIM: To study the effect of NaT on M. chimaera recovery and culture contamination. METHODS: Seventy-six paired HCU water samples (with and without NaT) were collected, processed and cultured simultaneously into Lowenstein-Jensen slants, Middlebrook 7H10 agar plates, and mycobacterial growth indicator tubes (MGITs), and incubated at 37°C. A subset of 31 paired samples was additionally cultured on MGITs and incubated at 30°C. FINDINGS: Of 76 samples incubated at 37°C in each of the three media, with and without NaT, M. chimaera was identified in at least one aliquot of 21 samples. CONCLUSION: The presence of NaT did not significantly increase the probability of recovering M. chimaera in a multi-variable conditional logistic model and culture contamination rates were similar between aliquots with and without NaT. In the subset of samples cultured on MGITs at both 30°C and 37°C, the presence of NaT again was not associated with M. chimaera recovery, but was significantly associated with reduced culture contamination.

Serendipitous evidence of T lymphocyte activation in close female relatives of patients with systemic lupus erythematosus.

A well-recognized characteristic of the autoimmune disease, systemic lupus erythematosus (SLE), is the high level of activated T cells present in the blood. Because of the increased size and granularity of activated T cells, in flow cytometry one might expect to find increased numbers of cells falling outside a standard light-scatter lymphocyte gate, and indeed we now report that the percentage of T lymphocytes in the gate (% TiG) was below the normal range in 23 of 58 (40%) female patients because of increased scatter values. However, the surprising additional observation was made that 18 of 30 (60%) female first-degree relatives of the patients also fell below the normal % TiG range, suggesting the presence of T cell activation in these relatives. This view is strengthened by the strong inverse correlation between plasma total immunoglobulin G(IgG), which was raised in some relatives, and % TiG, as T cell activation is a requirement for IgG production. Conversely, there was no correlation with IgM, which has no comparable link with T cell activation. While a definitive interpretation must await the demonstration of activation antigen expression in relatives, these findings suggest the existence of a T cell activation trait, not harmful in itself, which, however, contributes to the development of disease in patients with SLE.

[The dural arteriovenous fistula - an unimposing morphological correlate with imposing consequences]. / Die Durafistel - ein unscheinbares morphologisches Korrelat mit grossen Konsequenzen.

Dural arteriovenous fistulas (DAVFs) are abnormal arteriovenous shunts located within the dura mater representing approximately 10 - 15 % of all arteriovenous shunts in the central nervous system. The aetiology of spontaneous DAVFs remains to be elucidated. The symptoms associated with DAVFs can be highly variable and dependent upon the direction of the blood flow, the amount of arteriovenous shunting and the specific location of the fistula. Considering the diversity of clinical presentation in the setting of unremarkable imaging results, diagnosing a DAVF can be difficult. To avoid permanent neurological deficits due to DAVFs, it is important to consider the possibility of a DAVF whenever one encounters unclear neurological symptoms and to initiate appropriate diagnostic procedures including intraarterial DSA and MRI/MRA. The current DAVF classification accounts for the disparity of clinical symptoms, therapeutic/interventional implications as well as vital complications depending on each particular fistula subtype. While type I DAVFs drain anterogradely into a cerebral sinus and mainly cause functional deficits, the risk for severe intracerebral bleeding increases when DAVFs drain retrogradely (type II), or into cortical (types III and IV), perimedullar or radiculo-medullar veins (type V), respectively. In particular in the case of type IIb to V DAVFs, the appropriate treatment option is a complete fistula occlusion by transvenous embolization, transarterial glue or particulate embolization or surgery. In the following we systematically explain the differential anatomy underlying DAVFs and discuss possible symptoms and necessary diagnostic and therapeutic means. In that, we are seeking to increase attention for this rare, but clinically relevant neurological disease.