Effective use of medical-scientific Internet resources

Hintergrund: Das Medium Internet ist nicht hierarchisch strukturiert und unterscheidet sich daher von herk?mmlichen Wissensquellen. Die ansteigende Zahl medizinisch-wissenschaftlicher Webseiten bietet dem Augenarzt umfangreiche, jedoch nicht immer leicht zu erschlie?ende Informations- und Weiterbildungsm?glichkeiten. Material und Methode: Die Effektivit?t einer Internet-Recherche h?ngt vom Wissenstand über vorhandene Suchstrategien ab. Es werden Suchsysteme (Search engines, Kataloge, Datenbanken, Indizes) dargestellt sowie Hinweise für deren effektive Nutzung (Metasearch, Anwendung von Boolean-Operatoren, Wortgruppen-Suche) gegeben. Die Effizienz der Suche wird anhand konkreter Ergebnisse, deren Aktualit?t und der Anwenderfreundlichkeit der verwendeten Systeme bewertet. Neue, zukunftsweisende Applikationen wie SemioMap und Intelligent Agents werden vorgestellt. Ergebnisse und Schlu?folgerung: Bei Anwendung effektiver Suchstrategien stellt das Internet bereits heutzutage eine einfache und schnell zu nutzende Informationsquelle für den Arzt und Wissenschaftler dar. Die verfügbaren medizinisch-wissenschaftlichen Ressourcen leisten zunehmend aktuelle und praxisbezogene Beitr?ge zu fachspezifischer Weiterbildung und zukunftsorientierter Forschung.      

Excretion of modified nucleosides during development of malignant lymphomas in mice after whode body irradiation

Summary During x-ray-induced development of malignant lymphomas in mice their urinary excretion of eight modified nucleosides was monitored and the values were compared to the results of the histological examination of the animals at time of their sacrifice.It was found that the pathologically augmented excretion of modified nucleosides begins as much as several weeks before the malignant lymphomas can be diagnosed clinically. Thus some mice had increased levels of modified nucleosides even 10 weeks before sacrifice, though at the time of sacrifice the histological investigation reveled only some small foci of reticulum cell neoplasm in their spleen.It is therefore stressed that the usefulness of the determination of urinary modified nucleosides as an early noninvasive screening test for cancer in man and as an in vivo carcinogenicity test should be evaluated.Abbreviations pseudouridine - m¹A 1-methyladenosine - m⁵C 5-methylcytidine - m¹I 1-methylinosine - m¹G 1-methylguanosine - m²G N ²-methylguanosine - m²G N ²,N²-dimethylguanosine - ac⁴C N ⁴-acetylcytidine - mt⁶A N-(9--d-ribofuranosylpurine-6-yl)N-methylcarbamoyl) threonine - acp³U 3-(3-amino-3-carboxypropyl) uridine - SD standard deviation     

Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer.

PURPOSE: To determine the antitumor activity of ABX-EGF, a fully human monoclonal antibody to the epidermal growth factor receptor (EGFr), in previously treated patients with metastatic renal cell carcinoma, and to characterize its toxicity, immunogenicity, pharmacokinetics, and pharmacodynamics. PATIENTS AND METHODS: The antitumor activity, as well as the toxicity, pharmacokinetics, pharmacodynamics, and immunogenicity of ABX-EGF, were assessed. RESULTS: Eighty-eight patients were treated with ABX-EGF doses of 1.0, 1.5, 2.0, or 2.5 mg/kg weekly with no loading dose. EGFr immunostaining was performed on 76 tumor biopsy specimens (86%), and 69 (91%) scored positive. Major responses occurred in three patients, and two patients had minor responses. Forty-four patients (50%) also had stable disease at their first 8-week assessment, and the median progression-free survival (PFS) was 100 days (95% CI, 58 to 140 days). Low hemoglobin and high alkaline phosphatase predicted for short PFS. The principal toxicity, an acneiform rash, occurred in 68%, 95%, 87%, and 100% of patients who received at least three doses of ABX-EGF at 1.0, 1.5, 2.0, and 2.5 mg/kg/wk, respectively. A trend indicated that the severity of the rash may relate to PFS. No human antihuman antibodies were detected. ABX-EGF pharmacokinetics fit a model that incorporated both linear and saturable EGFr-mediated clearance mechanisms, and interindividual variability was low. At 2.5 mg/kg/wk, ABX-EGF concentrations throughout treatment exceeded those estimated to saturate nonlinear clearance and inhibit xenograft growth by 90%. CONCLUSION: ABX-EGF was generally well tolerated. The objective response rate was low in previously treated patients with metastatic renal cell carcinoma. Although skin rash may be a pharmacodynamic marker of drug action, its potential as a surrogate marker of clinical benefit requires further evaluation.     

Chromosomal instability rather than p53 mutation is associated with response to neoadjuvant cisplatin-based chemotherapy in gastric carcinoma.

PURPOSE: The objective of the study was to evaluate microsatellite alterations [microsatellite instability (MSI) and loss of heterozygosity (LOH)] and mutation in the p53 gene in relation to response and patient survival to a cisplatin-based neoadjuvant chemotherapy in gastric cancer. EXPERIMENTAL DESIGN: Fifty-three pretherapeutic gastric carcinoma biopsies were analyzed with 11 microsatellite markers. The entire coding region of the p53 gene (exons 2-11) was analyzed for mutations by denaturing high-pressure liquid chromatography and sequencing. p53 protein expression was evaluated by immunohistochemistry. Patients were treated with a cisplatin-based, neoadjuvant chemotherapy regimen. Therapy response was evaluated by computed tomography scan, endoscopy, and endoluminal ultrasound. The median follow-up of the patients was 45.6 months. RESULTS: p53 mutations were identified in 19 of the 53 (36%) analyzed tumors. No significant association with response or survival was found for p53 mutation or for p53 protein expression. MSI (either high-grade MSI or low-grade MSI) did not show a correlation with response. With respect to LOH, LOH at chromosome 17p13 showed a significant association with therapy response (P = 0.022) but did not reach statistical significance in terms of patient survival. The global LOH rate, expressed as fractional allelic loss (FAL), was assessed, and tumors were classified into tumors with a high (>0.5), medium (>0.25-0.5), and low (0-0.25) FAL value. A statistically significant association of FAL with therapy response was found (P = 0.003), with a high FAL being related to therapy response. The sensitivity, specificity, positive predictive value, and negative predictive value for FAL > 0.5 were 45%, 93%, 82%, and 72%, respectively. CONCLUSIONS: A high level of chromosomal instability (high FAL value) defines a subset of patients who are more likely to benefit from cisplatin-based neoadjuvant chemotherapy. p53 mutation status is not significantly associated with therapy response and is not a useful marker for response prediction.     

Letal verlaufende Varizellen nach Nierentransplantation

Zusammenfassung Wir berichten über ein 7 Jahre altes M?dchen, das 14 Tage nach einer Nierentransplantation an Varizellen erkrankte. Erste Symptome waren krampfartige Bauchschmerzen mit radiologischen Hinweisen auf einen Obturationssubileus bei Obstipation. Als nach abführenden Ma?nahmen keine Besserung auftrat, wurde eine Probelaparotomie mit Entfernung des Tenckhoff-Dialysekatheters durchgeführt. Dabei zeigte sich kein pathologischer Befund, insbesondere fanden sich keine Briden. Zwei Tage nach Beginn der abdominalen Symptomatik trat ein zun?chst uncharakteristisches Exanthem auf. Aus den sich in den n?chsten 12 h entwickelnden Bl?schen konnte Varicella-Zoster-Virus isoliert werden. Trotz hochdosierter Gabe von Aciclovir und Varicella-Zoster-Immunglobulin entwickelte sich ein fulminantes Leberversagen mit Verbrauchskoagulopathie. Die Patientin verstarb am 18. postoperativen Tag trotz intensiver supportiver Therapie im Multiorganversagen. Diskussion: Vor dem Hintergrund dieser letalen Varizelleninfektion wird auf die Komplikationen und die teilweise untypischen Verl?ufe von Windpocken bei immunsupprimierten Kindern hingewiesen. Eine aktive Impfung ist daher bei seronegativen Patienten vor einer geplanten Organtransplantation zu fordern.      

Syncopal migraine

Objective  

A subgroup of syncope patients report migraine headaches immediately preceding or following syncope, and some respond to anti-migrainous prophylactic agents. This study aimed to describe the frequency of migrainous features concurrent with episodes of syncope and to propose clinical criteria for assessing whether a migrainous mechanism might underlie syncope.     

Patient Characteristics as Indicator for Care Dependence after Hip Fracture: A Retrospective Cohort Study Using Health Insurance Claims Data From Germany

Objectives

Hip fractures are common consequences of falls in older adults and, among other negative health outcomes, often lead to care dependence in the long term. Until 2016, the German long-term care insurance classified care recipients according to a standardized classification system consisting of 3 care levels. It was based on required assistance in performing activities of daily living and assessed by a qualified physician or nurse. Thus, care level reflects the degree of care dependence. The aim of this study was to determine relevant patient characteristics, which are related to the likelihood of increasing care dependence in terms of worsening care level after hip fracture.

Association between Disability,Cognition, Fatigue,EQ-5D-3L Domains,and Utilities Estimated with Different Western European Value Sets in Patients with Multiple Sclerosis

Objectives

To assess the association between fatigue, cognition, domains of the EuroQol five-dimensional questionnaire (EQ-5D-3L), disability, and utilities estimated with several Western European value sets in patients with multiple sclerosis (MS).