Broadening the clinical spectrum for medical students towards primary care: a pre-post analysis of the effect of the implementation of a longitudinal clerkship in general practice.

BACKGROUND: Exposure to a broad spectrum of patient cases is a mainstay of undergraduate medical education. This study aimed to assess how many primary care-specific clinical pictures final-year medical students in traditional block rotations had encountered, and how this changed after a curricular change that included the implementation of a four-year longitudinal clerkship in primary care. METHODS: Final-year students before, and after, implementation of the clerkship were asked which of the clinical pictures most relevant to primary care they had seen. We compared the overall proportions of clinical pictures seen by the two cohorts. RESULTS: In the first cohort, 96 (66%) students responded, and 94 (65%) in the second. Before the curricular change, students had encountered a mean of 26.3 of the 34 primary care-specific clinical pictures (77.2%). After implementation of the longitudinal clerkship, this increased by 1.1 (4.2%, P = 0.038). Among the eight clinical pictures seen the least by students in the first cohort, we found a significant increase in the proportion of students seeing polymalgia rheumatica, frozen shoulder, epicondylitis and Dupuytren's contracture after the clerkship's implementation. CONCLUSION: The undergraduate longitudinal clerkship in primary care broadened the spectrum of clinical pictures seen by medical students, to include more clinical pictures commonly seen in primary care.

How the probability of presentation to a primary care clinician correlates with cancer survival rates: a European survey using vignettes.

OBJECTIVE: European cancer survival rates vary widely. System factors, including whether or not primary care physicians (PCPs) are gatekeepers, may account for some of these differences. This study explores where patients who may have cancer are likely to present for medical care in different European countries, and how probability of presentation to a primary care clinician correlates with cancer survival rates. DESIGN: Seventy-eight PCPs in a range of European countries assessed four vignettes representing patients who might have cancer, and consensus groups agreed how likely those patients were to present to different clinicians in their own countries. These data were compared with national cancer survival rates. SETTING: A total of 14 countries. SUBJECTS: Consensus groups of PCPs. MAIN OUTCOME MEASURES: Probability of initial presentation to a PCP for four clinical vignettes. RESULTS: There was no significant correlation between overall national 1-year relative cancer survival rates and the probability of initial presentation to a PCP (r = -0.16, 95% CI -0.39 to 0.08). Within that there was large variation depending on the type of cancer, with a significantly poorer lung cancer survival in countries where patients were more likely to initially consult a PCP (lung r = -0.57, 95% CI -0.83 to -0.12; ovary: r = -0.13, 95% CI -0.57 to 0.38; breast r = 0.14, 95% CI -0.36 to 0.58; bowel: r = 0.20, 95% CI -0.31 to 0.62). CONCLUSIONS: There were wide variations in the degree of gatekeeping between countries, with no simple binary model as to whether or not a country has a "PCP-as-gatekeeper" system. While there was case-by-case variation, there was no overall evidence of a link between a higher probability of initial consultation with a PCP and poorer cancer survival. KEY POINTS European cancer survival rates vary widely, and health system factors may account for some of these differences. The data from 14 European countries show a wide variation in the probability of initial presentation to a PCP. The degree to which PCPs act as gatekeepers varies considerably from country to country. There is no overall evidence of a link between a higher probability of initial presentation to a PCP and poorer cancer survival.

Physician's Prescribing Preference as an Instrumental Variable: Exploring Assumptions Using Survey Data.

BACKGROUND: Physician's prescribing preference is increasingly used as an instrumental variable in studies of therapeutic effects. However, differences in prescribing patterns among physicians may reflect differences in preferences or in case-mix. Furthermore, there is debate regarding the possible assumptions for point estimation using physician's preference as an instrument. METHODS: A survey was sent to general practitioners (GPs) in The Netherlands, the United Kingdom, New Zealand, Ireland, Switzerland, and Germany, asking whether they would prescribe levothyroxine to eight fictitious patients with subclinical hypothyroidism. We investigated (1) whether variation in physician's preference was observable and to what extent it was explained by characteristics of GPs and their patient populations and (2) whether the data were compatible with deterministic and stochastic monotonicity assumptions. RESULTS: Levothyroxine prescriptions varied substantially among the 526 responding GPs. Between-GP variance in levothyroxine prescriptions (logit scale) was 9.9 (95% confidence interval: 8.0, 12) in the initial mixed effects logistic model, 8.3 (6.7, 10) after adding a fixed effect for country and 8.2 (6.6, 10) after adding GP characteristics. The occurring prescription patterns falsified the deterministic monotonicity assumption. All cases in all countries were more likely to receive levothyroxine if a different case of the same GP received levothyroxine, which is compatible with the stochastic monotonicity assumption. The data were incompatible with this assumption for a different definition of the instrument. CONCLUSIONS: Our study supports the existence of physician's preference as a determinant in treatment decisions. Deterministic monotonicity will generally not be plausible for physician's preference as an instrument. Depending on the definition of the instrument, stochastic monotonicity may be plausible.

From chronic conditions to relevance in multimorbidity: a four-step study in family medicine.

BACKGROUND: Chronic conditions and multimorbidity (MM) are major concerns in family medicine (FM). OBJECTIVES: Based on the International Classification of Primary Care, Second Edition (ICPC-2), this study aimed to list (i)the chronic conditions and (ii)those most relevant to MM in FM. METHODS: A panel of FM experts used a four-step process to identify chronic conditions among ICPC-2 items and list chronic conditions most relevant in MM. They also evaluated the importance of eight criteria, previously identified in the literature, for characterizing chronic conditions. Step one involved a focus group of five experts. Steps two, three and four involved 10, 25 and 25 experts, respectively. They rated ICPC-2 items via an online questionnaire using a Likert scale from 1 (never chronic/irrelevant in MM) to 9 (always chronic/always relevant in MM). A median value cut-off was used to evaluate appropriateness of each item and the inter-percentile range adjusted for symmetry to determine the agreement/disagreement between experts. In parallel, in steps two and three, experts rated the importance of eight criteria to characterize chronic conditions, using a Likert scale from 1 (strongly disagree) to 9 (strongly agree). RESULTS: Of the ICPC-2's 686 items, experts identified 139 chronic conditions, of which 75 were deemed most relevant in the context of MM. Four of the eight criteria were retained as important to define chronic conditions: duration, sequelae, recurrence/pattern and the diagnosis itself. CONCLUSION: Using this list of 75 chronic conditions most relevant in the context of MM should enhance the validity of studies of MM in FM.

Clinical and haematological predictors of antibiotic prescribing for acute cough in adults in Swiss practices--an observational study.

BACKGROUND: Acute cough is a common problem in general practice and is often caused by a self-limiting, viral infection. Nonetheless, antibiotics are often prescribed in this situation, which may lead to unnecessary side effects and, even worse, the development of antibiotic resistant microorganisms worldwide. This study assessed the role of point-of-care C-reactive protein (CRP) testing and other predictors of antibiotic prescription in patients who present with acute cough in general practice. METHODS: Patient characteristics, symptoms, signs, and laboratory and X-ray findings from 348 patients presenting to 39 general practitioners with acute cough, as well as the GPs themselves, were recorded by fourth-year medical students during their three-week clerkships in general practice. Patient and clinician characteristics of those prescribed and not-prescribed antibiotics were compared using a mixed-effects model. RESULTS: Of 315 patients included in the study, 22% were prescribed antibiotics. The two groups of patients, those prescribed antibiotics and those treated symptomatically, differed significantly in age, demand for antibiotics, days of cough, rhinitis, lung auscultation, haemoglobin level, white blood cell count, CRP level and the GP's license to self-dispense antibiotics. After regression analysis, only the CRP level, the white blood cell count and the duration of the symptoms were statistically significant predictors of antibiotic prescription. CONCLUSIONS: The antibiotic prescription rate of 22% in adult patients with acute cough in the Swiss primary care setting is low compared to other countries. GPs appear to use point-of-care CRP testing in addition to the duration of clinical symptoms to help them decide whether or not to prescribe antibiotics.

General practitioner teachers' job satisfaction and their medical students' wish to join the field - a correlational study.

BACKGROUND: There will be increasing competition for young physicians worldwide as more and more physicians retire. While enthusiasm towards GP work is important for GP teachers as role models, satisfaction within the profession has declined. This study aims to determine if medical students' desire to become GPs is related to the job satisfaction of their teaching GPs and explore the factors tied to this job satisfaction. METHODS: In this cross-sectional, correlational study, teaching GPs of the University of Bern and the fourth year medical students completing internships with them filled in separate questionnaires. RESULTS: Whether or not the GP teacher is perceived by a student to be satisfied with her/his job is correlated to that student's satisfaction with the internship, which in turn, is correlated with student's wish to be a GP after the internship. Results show which factors are most related to GP job satisfaction and the effect of working hours and their composition. CONCLUSIONS: Medical students' perception of their GP teachers' job satisfaction positively affect their wish to become GPs, and their satisfaction with their internships adds to this. Enhancing the positive aspects of GP work, such as recognition, and improving negative ones, such as administrative duties, are necessary to attract medical students into the GP field.

Prenyl Ethers: Novel Fungal Volatiles Formed by Penicillium digitatum.

Prenyl ethyl ether (PEE) was previously described as the cause for a solvent-like off-note in ground hazelnuts, but its origin remained unclear. Investigations were carried out by analytical groups of Coop and Givaudan over four years to elucidate this phenomenon. From mouldy citrus fruits a strain of Penicillium digitatum was isolated and found to form PEE. Formation on citrus and other fruits was prominent and contributed to the particular smell of decayed fruits. Several strains of P. digitatum formed PEE, while other fungal species did not. In contrast to citrus fruit, prenyl methyl ether (PME) was formed as dominant prenyl ether on hazelnuts while only small amounts of PEE were found. PME has not been previously described as volatile metabolite of fungi or as a food-taint. Spiking experiments with deuterated ethanol showed that the ethyl group is likely incorporated into PEE via the aldehyde form. On hazelnuts strongly decayed by P. digitatum yet another prenyl ether was tentatively identified: Prenyl isopropyl ether. Prenyl ethers present a novel group of volatile metabolites of P. digitatum. They are likely typical for this species and have not been described before. Prenyl ethers seem to play a significant role in the smell of food decayed by P. digitatum and should be considered in cases of off-notes and taints.

Microalbuminuria and hyperfiltration in subjects with nephro-urological disorders.

BACKGROUND: Microalbuminuria (MA) has been shown to be an early biomarker of renal damage. It is postulated that MA is the early result of hyperfiltration, which could evolve into glomerular sclerosis and renal failure if hyperfiltration is left untreated. We hypothesized that MA is a good indicator of hyperfiltration in children with kidney disorders, obviating the need to calculate the filtration fraction (FF). METHODS: A total of 155 children or young adults were prospectively included [42 single kidney (SK), 61 vesico-ureteral reflux, 23 obstructive uropathies, 29 other kidney diseases]. We measured inulin, para-aminohippuric acid clearances, FF and MA. Prediction of hyperfiltration was explored by studying the association between the FF and other variables such as urinary albumin (Alb), urinary albumin-creatinine ratio (ACR) and creatinine clearance. RESULTS: A significant but weak association between urinary Alb or ACR and FF was found in subjects with an SK (Spearman correlation coefficients 0.32 and 0.19, respectively). Multivariate analysis also showed that urinary Alb and ACR significantly predict FF only in subjects with an SK (r(2) = 0.17, P = 0.01 and r(2) = 0.13, P = 0.02, respectively). This holds true only in subjects with an SK and inulin clearance >90 mL/min/1.73 m(2) (r(2) = 0.41, P < 0.001). There was no association between creatinine clearance and FF. CONCLUSIONS: MA is not associated with FF in our subjects with nephro-urological disorders, except in those with an SK, where the association is weak, indicating that MA is due to other mechanisms than high FF and cannot predict hyperfiltration in such groups.

Assessment of adult formulas for glomerular filtration rate estimation in children.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is an important diagnostic instrument in clinical practice. The National Kidney Foundation-Kidney Disease Quality Initiative (NKF-KDOQI) guidelines do not recommend using formulas developed for adults to estimate GFR in children; however, studies confirming these recommendations are scarce. The aim of our study was to evaluate the accuracy of the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, the Modification of Diet in Renal Disease (MDRD) formula, and the Cockcroft-Gault formula in children with various stages of chronic kidney disease (CKD). METHODS: A total of 550 inulin clearance (iGFR) measurements for 391 children were analyzed. The cohort was divided into three groups: group 1, with iGFR >90 ml/min/1.73 m(2); group 2, with iGFR between 60 and 90 ml/min/1.73 m(2); group 3, with iGFR of <60 ml/min/1.73 m(2). RESULTS: All formulas overestimate iGFR with a significant bias (p < 0.001), present poor accuracies, and have poor Spearman correlations. For an accuracy of 10 %, only 11, 6, and 27 % of the eGFRs are accurate when using the MDRD, CKD-EPI, and Cockcroft-Gault formulas, respectively. For an accuracy of 30 %, these formulas do not reach the NKF-KDOQI guidelines for validation, with only 25, 20, and 70 % of the eGFRs, respectively, being accurate. CONCLUSIONS: Based on our results, the performances of all of these formulas are unreliable for eGFR in children across all CKD stages and cannot therefore be applied in the pediatric population group.

The second-generation active Aß immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects.

Immunization against amyloid-ß (Aß) can reduce amyloid accumulation in vivo and is considered a potential therapeutic approach for Alzheimer's disease. However, it has been associated with meningoencephalitis thought to be mediated by inflammatory T-cells. With the aim of producing an immunogenic vaccine without this side effect, we designed CAD106 comprising Aß1-6 coupled to the virus-like particle Qß. Immunization with this vaccine did not activate Aß-specific T-cells. In APP transgenic mice, CAD106 induced efficacious Aß antibody titers of different IgG subclasses mainly recognizing the Aß3-6 epitope. CAD106 reduced brain amyloid accumulation in two APP transgenic mouse lines. Plaque number was a more sensitive readout than plaque area, followed by Aß42 and Aß40 levels. Studies with very strong overall amyloid reduction showed an increase in vascular Aß, which atypically was nonfibrillar. The efficacy of Aß immunotherapy depended on the Aß levels and thus differed between animal models, brain regions, and stage of amyloid deposition. Therefore, animal studies may not quantitatively predict the effect in human Alzheimer's disease. Our studies provided no evidence for increased microhemorrhages or inflammatory reactions in amyloid-containing brain. In rhesus monkeys, CAD106 induced a similar antibody response as in mice. The antibodies stained amyloid deposits on tissue sections of mouse and human brain but did not label cellular structures containing APP. They reacted with Aß monomers and oligomers and blocked Aß toxicity in cell culture. We conclude that CAD106 immunization is suited to interfere with Aß aggregation and its downstream detrimental effects.

Urodynamic score in children with lipomyelomeningocele: a prospective study.

PURPOSE: We assessed the correlation between urodynamic score and presence of symptoms in children with lipomyelomeningocele, and the usefulness of this measure in monitoring these children. MATERIALS AND METHODS: We prospectively evaluated 29 patients 1 month to 13 years old (mean 1.9 years) with lipomyelomeningocele from 1995 to 2010. A 4-parameter urodynamic score ranging from 0 to 17 was assigned to each patient at diagnosis and followup. Indications for surgery were presence of symptoms and signs or abnormal urodynamic score. Children were divided into 2 groups, symptomatic and asymptomatic. The latter group was further divided into operated and conservatively managed cases. Average followup was 6.7 years (range 2 to 16). RESULTS: The symptomatic group contained 11 children (38%) operated on at a mean age of 2.9 years. Mean followup was 6.7 years (range 2 to 12). All patients presented with an abnormal urodynamic score. Postoperative urodynamic score improved in 6 patients (55%), remained abnormal in 4 (36%) and deteriorated in 1 (9%). The asymptomatic group contained 18 patients, of whom 7 (39%) were operated on at a mean age of 1.4 years. Mean followup was 10 years (range 3 to 16). Postoperative score improved in 6 patients (86%) and remained unchanged in 1 (14%). A total of 11 cases (61%) were managed conservatively, with a mean followup 4.3 years (range 2 to 7). Of these patients 3 (27%) presented with late urodynamic score deterioration at 3, 5 and 6 years of followup while remaining asymptomatic. CONCLUSIONS: Urodynamic score is a useful tool in monitoring children with lipomyelomeningocele because it has a good correlation with the presence of symptoms.

[Perinatal asphyxia and neonatal hydronephrosis]. / Pédiatrie.

Perinatal asphyxia. Perinatal asphyxia remains one of the most important causes for high mortality and morbidity in the neonatal population. Despite intensive animal and clinical research in this field, no pharmocological strategy has been shown neuroprotective in humans. Moderate hypothermia for severely and moderately asphyctic babies has been aknowledged since a few years as therapeutical approach to improve the outcome of these infants, specifically the long-term follow up (18 months). Neonatal hydronephrosis. Neonatal hydronephrosis is a pathology that requires regular and efficient follow up by a multidisciplinary team. One of the causes of neonatal hydronephrosis is obstructive pathologies which may endanger the kidney. We have developed a strategy that allows a rapid diagnosis of obstructive pathologies with minimal radiological exams. Moreover, this strategy assures the coordination between obstetricians, neonatologists, pediatric urologists, and pediatric nephrologists.

[Update Medical Studies 2020: Bern]. / Update Medizinstudium 2020: Bern.

Update Medical Studies 2020: Bern Abstract. The education of the young Bernese medical students is problem-based as well as practice-oriented. The didactical concept of the Bachelor Studies is a guided self-study accompanied by concept lectures and interactive tutorials. The clinical skills are taught in a highly structured way, beginning with e-learning, seminars and Bedside Teaching. The Master Studies are based on evidence-based clinical education. The well-structured internships are the heart of the Bernese Master Studies; they enable the early inclusion of the students in the medical practice of the various healthcare disciplines. The communication trainings as well as the sonography courses are examples for the innovative development of the Bernese curriculum. The rotations in GP practices give an insight into the primary healthcare.

Looking back: twenty years of reforming undergraduate medical training and curriculum frameworks in Switzerland.

Introduction: To date, hardly any reports exist that outline the reforms in medical studies in Switzerland from the first partial reforms in the 1970s until today. Methods: This article outlines the recent history of medical curricula, their reforms in the early 1970s and, based on these, the key reasons for the major curricular reforms of the 2000s from the perspective of the authors. Results: The various projects, initiatives and legislative elements at the national level include the introduction of new quality control instruments - federal examination and programme accreditation, the introduction of a national catalogue of learning objectives and its two follow-up editions, as well as the implementation of the Bologna reform in undergraduate medical curricula. Examples of the key new elements found in all medical training in Switzerland include: the interdisciplinary orientation of learning content in organ and functional system-oriented subject areas or modules, the enhanced valorisation of practical clinical training, as well as the introduction of problem-oriented formats and the integration of partly formative, partly summative exams according to the format of the objective structured practical examination (OSCE). Characteristics unique to the four medical faculties and their medical training programme are also highlighted. Discussion: The described projects, initiatives and legislative elements have led to a dynamic, continuous development of medical curricula in Switzerland. The close cooperation between the faculties and the Federal Office of Public Health (FOPH) has also resulted in a redefinition of the roles and responsibilities of universities and the Federal Government according to the new Law on Medical Professions. This guarantees the medical faculties a great deal of autonomy, without neglecting quality assurance.

Evaluating a childhood obesity program with the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework.

Primary care providers can use behavioral lifestyle interventions to effectively treat children with overweight and obesity, but implementing these interventions is challenging. Most childhood obesity intervention evaluation studies focus on effectiveness. Few studies describe implementation. Our goal was to evaluate critical components of a childhood obesity intervention in primary care. We conducted a pilot implementation study of an existing structured lifestyle intervention in the Canton of Bern, Switzerland from 2013 to 2015. The intervention consisted of 10 sessions, led by a primary care physician. It included children aged 6-8 years old, with BMI over the 90th age-adjusted percentile. We used the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) evaluation framework to describe the pilot implementation study. We stratified description of RE-AIM components at the patient- and physician-level. For Reach: 864 children were screened; 65 were overweight; 394 physicians were invited to participate in the study. For Effectiveness: BMI z-score significantly decreased (-5.6%, p = 0.01). For Adoption: 14 participating physicians treated 26 patients. Implementation: the mean number of consultations was 8. For Maintenance: 9 (35%) children discontinued the intervention; 7 (50%) of physicians continued to apply at least one component of the intervention. The summarized components of the program within the RE-AIM framework suggest the program was successful. Stakeholders can use our results if they intend to disseminate and evaluate similar interventions in different settings.

Quantitative intrinsic auto-cathodoluminescence can resolve spectral signatures of tissue-isolated collagen extracellular matrix.

By analyzing isolated collagen gel samples, we demonstrated in situ detection of spectrally deconvoluted auto-cathodoluminescence signatures of specific molecular content with precise spatial localization over a maximum field of view of 300 µm. Correlation of the secondary electron and the hyperspectral images proved ~40 nm resolution in the optical channel, obtained due to a short carrier diffusion length, suppressed by fibril dimensions and poor electrical conductivity specific to their organic composition. By correlating spectrally analyzed auto-cathodoluminescence with mass spectroscopy data, we differentiated spectral signatures of two extracellular matrices, namely human fibrin complex and rat tail collagen isolate, and uncovered differences in protein distributions of isolated extracellular matrix networks of heterogeneous populations. Furthermore, we demonstrated that cathodoluminescence can monitor the progress of a human cell-mediated remodeling process, where human collagenous matrix was deposited within a rat collagenous matrix. The revealed change of the heterogeneous biological composition was confirmed by mass spectroscopy.

The effect of enzymatically degradable poly(ethylene glycol) hydrogels on smooth muscle cell phenotype.

The formation of scar tissue due to dedifferentiation of smooth muscle cells (SMCs) is one of the major issues faced when engineering bladder tissue. Furthermore, cell sources for regenerating the SMC layer are also limiting. Here we explore if human mesenchymal stem cells (MCSs), cultured in enzymatically degradable poly(ethylene glycol) (PEG) hydrogel scaffolds can be differentiated into SMC-like cells. We explored the degree to which a less synthetic SMC phenotype can be achieved when primary human SMCs are cultured within these scaffolds, It was observed that when both MSCs and SMCs are cultured in the PEG hydrogel scaffolds, but not on traditional tissue culture plastic, they up-regulate markers associated with the less synthetic SMC phenotype, decreased expression of alpha(5) integrin and THY-1, and increased expression of alpha-smooth muscle actin (alphaSMA) and myosin. Furthermore, we show that MSCs and SMCs cultured in the PEG hydrogels are able to proliferate and express matrix metalloproteinases for up to 21d in culture, the duration of the study. This study addresses the importance of the cellular microenvironment on cell fate, and proposes synthetic instructive biomaterials as a means to direct cell differentiation and circumvent scar tissue formation during bladder reconstruction.

Management of cryptorchidism in children: guidelines.

QUESTION: To develop clinical guidelines for the management of cryptorchidism in pre-pubertal boys, from early diagnosis through therapy to long-term follow-up and prognosis. METHOD: Systematic review of articles from the medical literature, referenced since 1966, using validated search strategies through the following databases: Medline, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, EMBASE, DARE, ACP Journal Club, National Guidelines Clearinghouse, Guidelines International Network. Relevant articles published after 1988 were taken as the basis for the statements. Each statement was graded on the basis of the study design and on its methodological quality (GRADE approach). A multidisciplinary panel of local experts discussed and evaluated each statement on the strength of this evidence. RESULTS: 28 statements based on the best available evidence were drafted. The experts agreed with all but two statements, which were rated uncertain. CONCLUSIONS: Cryptorchidism is best diagnosed clinically, and treated by surgical orchiopexy at age 6-12 months, without a routine biopsy. If no testis is palpable, or if other signs of hypovirilisation such as hypospadias are present, the chromosomal sex and hormonal status must be assessed. Laparoscopy is the best way of diagnosing and managing intra-abdominal testes.

In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe.

As Alzheimer's disease pathogenesis is associated with the formation of insoluble aggregates of amyloid beta-peptide, approaches allowing the direct, noninvasive visualization of plaque growth in vivo would be beneficial for biomedical research. Here we describe the synthesis and characterization of the near-infrared fluorescence oxazine dye AOI987, which readily penetrates the intact blood-brain barrier and binds to amyloid plaques. Using near-infrared fluorescence imaging, we demonstrated specific interaction of AOI987 with amyloid plaques in APP23 transgenic mice in vivo, as confirmed by postmortem analysis of brain slices. Quantitative analysis revealed increasing fluorescence signal intensity with increasing plaque load of the animals, and significant binding of AOI987 was observed for APP23 transgenic mice aged 9 months and older. Thus, AOI987 is an attractive probe to noninvasively monitor disease progression in animal models of Alzheimer disease and to evaluate effects of potential Alzheimer disease drugs on the plaque load.

(Poly)acrylonitrile-based hydrogel as a therapeutic bulking agent in urology.

Vesicoureteral reflux and urinary incontinence can be treated by endoscopic injection. Injectables such as collagen and hyaluronic acid-dextranomer are commonly used, however are not offering optimal therapeutic effect yet. In the present study a novel application for poly(acrylonitrile)-based hydrogel (Hypan), already tested in other clinical indications, has been investigated for its aptitude as an injectable bulking agent. This non-degradable, extremely hydrophilic hydrogel has the capacity of a 6-fold swelling once implanted into the body, assuring the bulking effect. Deposits of this bulking agent have been implanted into the submucosal space of the bladder of 6 minipigs and the histological reaction, as well as the physical implant behavior have been studied over a time period of 6 months. The implants have developed the desired bulking effect by the above-described hydrophilic swelling. They have been enclosed into a fine fibrous tissue capsule and provoked a very limited inflammatory reaction. This study has showed that poly(acrylonitrile)-based hydrogel implants injected into the bladder are well tolerated and, due to their defined bulking ability, feasible for the treatment of vesico-ureteral reflux and urinary incontinence. To determine the therapeutic efficiency of this treatment the implants will be studied in a vesicoureteral reflux and urinary incontinence animal model.