Epidermal growth factor receptor levels increase but epidermal growth factor receptor ligand levels decrease in mouse mammary tumors during progression from hormone dependence to hormone independence

Summary Twenty-six serially transplanted Grunder (GR) strain mouse mammary tumors were analyzed for epidermal growth factor receptor (EGFR) and EGFR-ligand levels, in addition to steroid hormone receptors (estrogen receptor, ER, progesterone receptor, PgR). In concordance with earlier studies, hormone dependent (HD) and hormone responsive (HR) tumors were found to be positive for both ER and PgR, whereas hormone independent (HI) tumors contained only 30% of the ER concentration that was found in the HD tumors. PgR was undetectable in HI tumors. HI tumors contained 2.5 to 3-fold higher EGFR levels than HD/HR tumors, an observation which shows remarkable concordance with studies on EGFR in human breast cancer. On the other hand, the level of EGFR-ligand(s) was positively associated with ER levels and was three-fold higher in HD/HR tumors than in HI tumors. The low EGFR in HD/HR tumors relative to HI tumors may be the result of downregulation by EGFR ligands produced under ER control. During progression to hormone independence this downregulation of EGFR is then abolished in absence of ER. The increase in EGFR may therefore be a secondary effect rather than a key event in the progression to hormone independence in this mouse mammary tumor model.Abbreviations EGF Epidermal Growth Factor - EGFR Epidermal Growth Factor Receptor - ER Estrogen Receptor - PgR Progesterone Receptor - HD Hormone Dependent - HR Hormone Responsive - HI Hormone Independent - HAP Hydroxylapatite - DCC Dextran Coated Charcoal - GR Grunder - TGF- Transforming Growth Factor-     

Factors Influencing the Growth in Knowledge of Trainees in General Practice

Objectives: The relation between the content of postgraduate training for general practice and the outcome in terms of the growth in knowledge of trainees was investigated. The training variables included were: (1) the number of patients seen per day, (2) the trainer, (3) the practice and (4) the theoretical curriculum.Methods: Subjects were 58 trainee-trainer pairs. Growth in knowledge was assessed by two written tests administered with eight months interval. Training variables were evaluated by means of questionnaires and logbook-registration. The correlation was explored between each of the training variables and the knowledge tests scores. To correct for interactional effects, a step-wise multiple regression analysis was performed with the second test as dependent variable and the first test as well as the training variables as independent variables.Results: Significant growth in knowledge was demonstrated. Non of all training variables investigated explained the variance in scores on the second test equally good or better than the scores on the entry test.Conclusions: The impact of the separate training-components on the growth in knowledge, remains unclear. We may speculate, that the sort of knowledge assessed with the written literature based true/false test is different from the sort of knowledge transferred during every day training: evidence based knowledge versus experience based knowledge. Equally valid is the conclusion that these findings fit into the theory that in adult learning the outcome is more learner than teacher dependent.This revised version was published online in September 2005 with corrections to the Cover Date.     

Thallium-201 single-photon emission computed tomography as an early predictor of outcome in recurrent glioma.

PURPOSE: With limited response rates and potential toxicity of chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. Currently, the assessment of treatment response in glioma patients is based on the combination of radiologic and clinical findings. However, response monitoring with computed tomography (CT) or magnetic resonance imaging (MRI) is hampered by several pitfalls and is prone to interobserver variability. The aim of this study was to establish the value of thallium-201 single-photon emission computed tomography (201Tl-SPECT) as a predictor of overall survival and response to chemotherapy in recurrent glioma, and to compare the value of 201Tl-SPECT with that of CT and MRI. PATIENTS AND METHODS: We studied patients who underwent CT or MRI and 201Tl-SPECT before chemotherapy (n = 57), and patients who also had undergone CT or MRI and 201Tl-SPECT after two courses of chemotherapy (n = 44). The value of the radiologic variables (CT-MRI tumor size, 201Tl-SPECT tumor size, and maximal tumor intensity) at baseline and at follow-up in predicting overall survival, and the percentage of patients alive and progression-free at 6 months (APF6) were examined using Cox regression and logistic regression analysis. RESULTS: Both at baseline and at follow-up, 201Tl-SPECT maximal tumor intensity was the strongest predictive variable and was inversely related to overall survival and APF6. In particular, progression of maximal tumor intensity after two courses of chemotherapy was a powerful predictor of poor outcome. CONCLUSION: 201Tl-SPECT is superior to conventional CT-MRI in the early prediction of overall survival and response to chemotherapy in patients with recurrent glioma.     

''I found myself to be a down to earth Dutch girl'': a qualitative study into learning outcomes from international traineeships

OBJECTIVE: To explore learning outcomes from international traineeships for undergraduate medical students. METHODS: In-depth interviews were conducted with 24 undergraduate medical students at Maastricht University Medical School, The Netherlands. The 24 subjects were selected by purposeful sampling. RESULTS: Students reported meaningful learning outcomes in 6 domains: medical knowledge; skills; international health care organisation; international medical education; society and culture, and personal growth. DISCUSSION: International traineeships appear to provide good opportunities for students to meet the requirements of globalisation as well as some of the generic objectives of undergraduate medical education. The tentative findings of this study need to be confirmed by further studies.     

Identifying platelet-derived factors as amplifiers of B. burgdorferi-induced cytokine production

Previous studies have shown that monocytes can be ‘trained’ or tolerized by certain stimuli to respond stronger or weaker to a secondary stimulation. Rewiring of glucose metabolism was found to be important in inducing this phenotype. As we previously found that Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme borreliosis (LB), alters glucose metabolism in monocytes, we hypothesized that this may also induce long-term changes in innate immune responses. We found that exposure to B. burgdorferi decreased cytokine production in response to the TLR4-ligand lipopolysaccharide (LPS). In addition, B. burgdorferi exposure decreased baseline levels of glycolysis, as assessed by lactate production. Using GWAS analysis, we identified a gene, microfibril-associated protein 3-like (MFAP3L) as a factor influencing lactate production after B. burgdorferi exposure. Validation experiments proved that MFAP3L affects lactate- and cytokine production following B. burgdorferi stimulation. This is mediated by functions of MFAP3L, which includes activating ERK2 and through activation of platelet degranulation. Moreover, we showed that platelets and platelet-derived factors play important roles in B. burgdorferi-induced cytokine production. Certain platelet-derived factors, such chemokine C-X-C motif ligand 7 (CXCL7) and (C-C motif) ligand 5 (CCL5), were elevated in the circulation of LB patients in comparison to healthy individuals.     

Coccidioidomycosis Infection of a Total Knee Arthroplasty in a Nonendemic Region

Fungal prosthetic joint infections are rare and difficult to treat. There is an ongoing discussion about the type and duration of antifungal treatment and the necessity of prosthesis removal. We report the first European case of an infected total knee arthroplasty with Coccidioides immitis. Treatment consisted of lifelong treatment with oral fluconazole at a dose of 400 mg/d, without total knee arthroplasty removal. After 6 months, the initial complaints of pain and swelling were completely resolved. This case report clearly states that a travel history and culturing for fungi are helpful in patients with persisting complaints after joint arthroplasty.     

Galen Wagner,M.D., Ph.D. (1939–2016) as international mentor of young investigators in electrocardiology

This paper describes a substantial part of the international mentoring network of students and young investigators in electrocardiology that developed around Dr. Galen Wagner (1939–2016), including many experiences of his mentees and co-mentors.The paper is meant to stimulate thinking about international mentoring as a means to achieve important learning experiences and personal development of young investigators, to intensify international scientific cooperation, and to stimulate scientific production.