[Deep skin infection with Scedosporium apiospermum-infection in a renal transplant patient]. / Scedosporium-apiospermum-Infektion bei einem nierentransplantierten Patienten.

A 57-year-old immunosuppressed patient presented with multiple erythematous papules and pustules as well as isolated ulcerations on the right lower leg and subcutaneous nodules on the right thigh. The biopsy revealed granulomatous inflammation with numerous fungal hyphae, which were IDentified as Scedosporium apiospermum by PCR. He was treated with voriconazole 2 × 200 mg daily as well assurgical debridement. Scedosporium apiospermum is a rare pathogenic agent of deep mold fungus infections. Skin infections with Scedosporium apiospermum are underdiagnosed because of different clinical manifestations. In immunosuppressed patients, an infection represents a potentially life-threatening complication. Precise identification of the agent with introduction of antimycotic therapy appears to be pivotal to prevent fulminant disease.

Combination of C-TRUS with multiparametric MRI: potential for improving detection of prostate cancer.

PURPOSE: To improve the detection of prostate cancer, especially in pre-biopsied patients, a guided biopsy based on radiologic findings is an option. We addressed the question, whether the combination of multiparametric MRI and computerized transrectal ultrasound (C-TRUS) improves the detection of prostate cancer. METHODS: Twenty patients suspicious of having prostate cancer were included. Seventeen patients were pre-biopsied once or more. Each patient was examined by multiparametric MRI and C-TRUS, followed by a guided transrectal prostate biopsy series. Patients were stratified in a "low-risk" and "high-risk" group. The results were analyzed using descriptive statistics. RESULTS: In 58 % (11 pat.) of patients, prostate cancer was found. In the "high-risk" group, biopsy in 73 % (8 pat.) of patients was positive for prostate cancer. All prostate cancer patients were found by C-TRUS-guided biopsies, whereas MRI did not reveal cancer in 27 %. 72 % (8 pat.) of patients had undergone radical prostatectomy. 65 % (6 pat.) had higher tumor stages after prostatectomy and 62.5 % (5 pat.) had higher Gleason-score. CONCLUSIONS: Combination of multiparametric MRI and C-TRUS seems to improve detection of prostate cancer, especially in high-risk patients. Detection rates of C-TRUS in this study could confirm those of the primary C-TRUS studies. The benefit of MRI is the additional visualization of the tumor extension. The technique is an option for pre-biopsied patients. Both imaging methods often fail to predict correct tumor stage, but further studies are necessary.

[Actinic keratoses. Pathogenesis, clinical aspect and modern therapeutic options]. / Aktinische Keratosen. Pathogenese, Klinik und moderne Therapieoptionen.

Actinic keratoses primarily affect fair-skinned individuals over 50 years of age. Due to demographic changes, the prevalence of actinic keratoses has increased over the last years. An established risk factor is chronic UV-exposure (outdoor workers) inducing mutations of the tumor suppressor gene TP53 and the oncogene H-ras. This leads to an intraepidermal proliferation of atypical keratinocytes. The term "field cancerization" characterizes the presentation of multiple actinic keratoses in UV-exposed areas. Actinic keratoses are also termed squamous cell carcinoma (SCC) in situ. The risk for actinic keratoses to turn into a SCC is 6-10 %. Treatment should be provided early in the disease course to avoid the possibility of invasive growth. In recent years, multiple therapeutic options have been established. Depending on the clinical extent, lesion- or field-directed therapies with excellent clinical response and cosmetic results are available.

SIMONA 1.0: an efficient and versatile framework for stochastic simulations of molecular and nanoscale systems.

Molecular simulation methods have increasingly contributed to our understanding of molecular and nanoscale systems. However, the family of Monte Carlo techniques has taken a backseat to molecular dynamics based methods, which is also reflected in the number of available simulation packages. Here, we report the development of a generic, versatile simulation package for stochastic simulations and demonstrate its application to protein conformational change, protein-protein association, small-molecule protein docking, and simulation of the growth of nanoscale clusters of organic molecules. Simulation of molecular and nanoscale systems (SIMONA) is easy to use for standard simulations via a graphical user interface and highly parallel both via MPI and the use of graphical processors. It is also extendable to many additional simulations types. Being freely available to academic users, we hope it will enable a large community of researchers in the life- and materials-sciences to use and extend SIMONA in the future. SIMONA is available for download under http://int.kit.edu/nanosim/simona.

[Anetoderma with positive Borrelia serology]. / Anetodermie bei positiver Borrelienserologie.

Anetoderma is an uncommon disease characterized by multiple circumscribed atrophic, herniated skin lesions on trunk, thighs and upper arms caused by loss of elastic fibers. Associations with autoimmune diseases or infections, especially spirochetal infections, have been described. We report a case of anetoderma with an increased serum Borrelia burgdorferi IgM-titers. After treatment with doxycycline 200 mg/day for three weeks, the progression of the disease stopped and no new lesions appeared.

Vacuolar p;erfusion technique for Nitella internodal cells.

A method has been developed for continuous control of the vacuolar composition of the giant internodal cells of the alga Nitella. During perfusion of the vacuole, cyclosis and spontaneous action potentials were evident, while the membrane potential and resistance were 86 and 58 percent of normal, respectively. The membrane system remained intact and functional during perfusion.

Attenuation of monocyte proinflammatory cytokine responses to Neisseria meningitidis in children by erythropoietin.

Meningococcal disease is a leading infectious cause of death in children in industrialized countries. The induction of high levels of proinflammatory cytokines has been implicated in the pathogenesis of Neisseria meningitidis-related multi-organ failure. Here, we demonstrate that N. meningitidis serotypes A and B induce significantly higher levels of tumour necrosis factor (TNF)-alpha positive cells in vitro in infants and young children compared with adults (serotype A/B; infants: 64.9%/63.9%; children: 77.8%/64.3% versus adults: 27.7%/32%; P < 0.005). Serotype A induces also higher levels of interleukin (IL)-6 positive cells in neonates and infants compared with adults (serotype A; newborn 55.4%; infants 58.8% versus adults 49%; P < 0.05). Treatment with human recombinant erythropoietin in vitro resulted in significant attenuation of the N. meningitidis-induced proinflammatory response in all age groups (reduction rate of erythropoietin for IL-6 after stimulation with serotype B: newborn 28%, infants 15%, children 23% and adults 28% and for TNF-alpha after stimulation with serotype B: newborn 27%, infants 22%, children 20% and adults 28%; P < 0.05). We conclude that (i) Neisseria meningitidis induces a higher TNF-alpha response in infants and children compared with adults and (ii) erythropoietin was able to attenuate IL-6 and TNF-alpha production in all investigated age groups. These data may explain the high incidence of meningococcal infection in infants and makes erythropoietin a potentially attractive candidate for interventional strategies in an otherwise devastating course of the disease.

[Aggressive course of a malignant alveolar soft tissue sarcoma]. / Aggressive Verlaufsform eines malignen alveolären Weichteilsarkoms.

Alveolar soft part sarcoma is a rare soft tissue tumor. Most patients who are affected by this sarcoma are between 15 and 35 years old. The tumor is characterized by its uncommon location of metastasis. Publications concerning this sarcoma subform are rare and the best therapeutic procedure is not yet clear. Surgical excision, radiation and chemotherapy are performed, whereas complete surgical excision achieves the best results in long-term follow-up. We report a patient's history who rapidly died of his sickness despite the low initial tumor stage.

Arterial hypotension and prerenal failure in an extremely preterm infant associated with oral sildenafil.

We report significant hypotension and prerenal failure in an extremely preterm infant following two doses of oral sildenafil that warranted discontinuation of the drug and treatment with inotropes. Blood pressure and urine output normalized after 24 h of withdrawal of the oral drug. Sildenafil should be used cautiously in extremely preterm infants early in the neonatal course, where there is limited data on its efficacy and safety.

Does erythropoietin protect the preterm brain?

There is a high incidence of hypoxic-ischaemic brain injury and intraventricular haemorrhage in newborn infants, particularly those born preterm. Many die during the newborn period or suffer permanent neurodevelopmental handicaps. Hypoxic brain injury develops over several hours and could potentially be influenced by intervention. At present, no drug exists that effectively prevents infant brain injury or ameliorates detrimental neurodevelopmental effects. The hypothesis is put forward that systemic administration of recombinant human erythropoietin positively affects the neurodevelopmental outcome of high risk preterm infants affected by brain injury. A multicentre, randomised, placebo controlled study is proposed to prospectively test this hypothesis.

Autism spectrum disorder in children born preterm-role of exposure to perinatal inflammation.

Autism Spectrum Disorder (ASD) is the collective term for neurodevelopmental disorders characterized by qualitative impairments in social interaction, communication, and a restricted range of activities and interests. Many countries, including Australia, have reported a dramatic increase in the number of diagnoses over the past three decades, with current prevalence of ASD at 1 in every 110 individuals (~1%). The potential role for an immune-mediated mechanism in ASD has been implicated by several studies, and some evidence suggests a potential link between prenatal infection-driven inflammation and subsequent development of ASD. Furthermore, a modest number of contemporary studies have reported a markedly increased prevalence of ASD in children born preterm, who are at highest risk of exposure to perinatal inflammation. However, the mechanisms that underpin the susceptibility to infection-driven inflammation during pregnancy and risk of preterm birth, and how these intersect with the subsequent development of ASD in the offspring, is not understood. This review aims to summarize and discuss the potential mechanisms and evidence for the role of prenatal infection on the central nervous system, and how it may increase the susceptibility for ASD pathogenesis in children born preterm.

[Quality and objectifiability of training and advanced training in urology]. / Qualität und Objektivierbarkeit der Aus- und Weiterbildung in der Urologie.

The attraction to study medicine has not changed, however we are facing a lack of trainees especially in surgical subspecialties like urology. Possible explanations are a 70% proportion of female students and different views on the work-life balance in the future. A high burden of theory and unrealistic multiple choice examinations support those who can learn but there are no objective and reproducible criteria to recognize the competence of a good physician early in the career. This problem continues during residency, especially in surgical subspecialities. The different medical boards in Germany responsible for the training programs have no concepts. Many attempts in other countries to objectively measure surgical skills have so far been ignored. If we do not want to lose our traditionally high competence in medicine we should join those who attempt to improve teaching and to use methods for selecting suitable candidates for surgery as soon and as objectively as possible.

[Education of medical students in urology in Germany: present status]. / Ausbildung von Medizinstudenten auf dem Gebiet der Urologie in Deutschland : Aktuelle Situation.

BACKGROUND: There is a growing demand for doctors in Germany and diseases of the genitourinary tract have become more prevalent in recent years. Politicians plan to increase the number of students in an already heavily overloaded system but data on quality and structure of medical education in Urology are lacking. The purpose of this study was to investigate the extent and quality of undergraduate medical education in urology. MATERIAL AND METHODS: Departments of Urology at German University Hospitals were surveyed using a questionnaire. Questions covered four different fields of medical education and answers were analyzed by descriptive statistics. RESULTS: Of the teachers involved in medical education 97% are physicians and 4% of these have special didactic qualifications. On average 1 teacher is responsible for 13 students and 44% of departments also have to carry out medical duties during teaching lessons. More than half of the departments offer modern learning forms, such as e-learning, problem-oriented learning or skills laboratory training. CONCLUSIONS: Urology departments at German University Hospitals spend much time on medical education. Nearly all physicians are involved in medical education, whether they are experienced or not and in many cases teaching is carried out in parallel to patient care. In more than half of the cases modern education tools were employed which implies a good standard of quality but there are no data on outcome.

[Is the training and continuing education for urologists in Germany still up to date?]. / Ist die Aus- und Weiterbildung zum Urologen in Deutschland noch zeitgemäß?

Besides its role in bladder and kidney cancer, urology plays a leading part in oncology particularly with regard to prostate cancer, the most frequent malignant tumor found in men. The multitude of hereditary anomalies of the urogenital tract and the resultant medical conditions, the importance of urinary tract infections including the still deadly urosepsis, urolithiasis which has become as widespread a condition as diabetes mellitus, and urinary incontinence as an increasing problem of a continuously aging population play such a large role in routine practice that every practicing physician must acquire the necessary skills for appropriate diagnosis and treatment. Is our current curriculum for training and continuing education adequate for this task?The primary goal of a meaningful program for continuing education must be to impart the corresponding qualities to young colleagues to ensure optimal patient care. The specialist certification exam itself should invariably be based nationwide on an objective written test: the existing European Board of Urology exam would be ideally suited to facilitate a comparison with other countries across Europe.

Reduced IL-10 production and -receptor expression in neonatal T lymphocytes.

AIM: To further evaluate the underlying mechanism of a formerly demonstrated immature anti-inflammatory response in neonates (1). METHODS: Interleukin (IL)-10 production was measured by enzyme-linked immunosorbent-assay (ELISA) after anti-CD3/anti-CD28 costimulation of neonatal and adult T cells. IL-10 receptor expression on T lymphocytes, B lymphocytes and monocytes were analysed by flow cytometry in neonates and adult controls. RESULTS: After anti-CD3/anti-CD28 costimulation, IL-10 production of neonatal T lymphocytes was profoundly reduced (median 247 pg/mL vs. 1062 pg/mL, p < 0.0001). IL-10 receptor expression was diminished on neonatal T lymphocytes compared to adults (3% vs. 39.5% IL-10 receptor positive lymphocytes; p < 0.0001). On neonatal B lymphocytes and monocytes the IL-10 receptor expression was comparable to adult controls. CONCLUSION: The strongly reduced IL-10 receptor expression on the main immune regulative T lymphocytes in conjunction with a significantly impaired synthesis of IL-10 may play a crucial role in the formerly demonstrated deficient anti-inflammatory immune response in neonates.

Cytokine responses correlate differentially with age in infancy and early childhood.

The functional differentiation of immune cells at early age plays a central role in immune physiology, e.g. for the sufficient eradication of pathogens. However, imbalances in effector cell responses may also have an impact in the pathophysiology of childhood diseases such as atopy and autoimmune disorders. As information on immune cell responses in infancy and early childhood is scarce, we conducted an observational, cross-sectional study in healthy newborns (n = 18), infants and young children (n = 54) aged 1-96 months and adult controls (n = 19) to assess cytokine mRNA and protein expression upon phorbol 12-myristate 13-actate/ionomycin stimulation and LPS-induced IL-12 expression in monocytes. The intracellular expression of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha (R = 0.748, P < 0.0001; R = 0.784, P < 0.0001, respectively) and interleukin (IL)-2 protein expression (R = 0.384, P = 0.008) was demonstrated to increase progressively with age. While a correlation between IL-4 protein expression and age was noted (R = 0.342, P = 0.007), the levels of IL-5 and IL-10 protein expression tended to be regulated on an individual basis during infancy and early childhood. An age correlation was also observed for intracellular IL-12 expression (R = 0.331, P = 0.009) in monocytes. These findings are valuable for further assessment of normal variations and maturation processes in immune cell responses and for the clinical-therapeutic monitoring of immunological status in various childhood diseases.

Failure to thrive in a 14-month-old boy with lymphopenia and eosinophilia.

We describe the case of a 14-month-old boy with delayed-onset SCID due to ADA-deficiency which was masqueraded only by failure to thrive. Remarkably, the child had no serious infections and an adequate immune response. However, absolute lymphopenia, eosinophilia and absent thymus on chest x-ray were indicative for immunodeficiency.

Immature anti-inflammatory response in neonates.

The inflammatory response plays a major role in the induction of several neonatal diseases. We hypothesize that an imbalance between the pro- and anti-inflammatory response is crucial for the previously shown enhanced production of proinflammatory cytokines in term and preterm infants during infection. To test this hypothesis, we compared the capacity to produce the main anti-inflammatory cytokines IL-10 and TGF-beta in term infants, preterm infants and adults at different levels of synthesis by quantitative real time reverse-transcribed PCR, flow cytometry, as well as enzyme-linked immunoassay. Term and preterm infants showed a profoundly diminished IL-10 mRNA-expression and IL-10 production after stimulation. In addition, the amount of TGF-beta-positive lymphocytes was significantly less in neonates than adults. Furthermore, there was a considerably lower inhibition of production of IL-1alpha, IL-6, IL-8 and TNF-alpha by the use of recombinant IL-10 in term and preterm infants compared with adults. These results demonstrate not only a diminished anti-inflammatory capacity but also a reduced response to anti-inflammatory stimuli in term and preterm infants. From these data we conclude that neonates display an immature compensatory anti-inflammatory response syndrome (CARS) which may predispose preterm infants to harmful effects of proinflammatory cytokines resulting in severe organ sequelae during infection.