Die Bedeutung der topischen neurologischen Diagnostik bei Kindern nach einem Geburtstrauma

Zusammenfassung Die neurologische Untersuchung und Differenzialdiagnostik bei Neugeborenen und S?uglingen wird aus der Sicht der Manualmedizin besprochen. Die Zuordnung der neurologischen Befunde zu einer neurologischen Kategorie oder zu einem neurologischen Syndrom bzw. zur Kombination mit den funktionellen vertebrogenen St?rungen bietet für die Manualmediziner erhebliche Vorteile an. Deshalb wird au?er einer traditionellen manuellen Untersuchung sowie der Auswertung des R-Bildes auch eine gründliche kinderneurologische Untersuchung praktiziert sowie empfohlen. Beim Vorliegen des vollst?ndigen klinischen neuroorthop?dischen Bildes kann weiterhin beurteilt werden, ob die funktionelle vertebrogene St?rung mit einer eher zentralen L?sion bei einem Hirnschaden oder mit einer perinatalen Rückenmarkssch?digung kombiniert wird. Das diffentialdiagnostische Vorgehen gibt eine wichtige Entscheidungshilfe für die richtige Auswahl der durchzuführenden Therapien und macht verl?ssliche Aussagen zur Prognose m?glich.     

Cardiovascular biomarkers in patients with psoriasis

Psoriasis is a systemic inflammatory disease of the skin with associated comorbidity. Severe forms of psoriasis are associated with increased mortality, which might be due to cardiovascular (CV) comorbidity. In this study, we investigated in 79 patients with psoriasis compared to 80 healthy volunteers different biomarkers that play a role in vascular disease and inflammation, such as C‐reactive protein (CRP), human soluble CD40 ligand (sCD40L), oxidized low‐density lipoprotein (ox‐LDL), human matrix Gla protein (MGP) and fetuin‐A. Our results showed that CRP (P < 0.0001), sCD40L (P < 0.0001) and MGP (P < 0.0001) were increased in the patient cohort. Fetuin‐A showed decreased serum levels in patients with psoriasis (P < 0.0001), whereas ox‐LDL did not show any significant difference. In multivariate analyses controlling for sex, age and BMI, these findings were confirmed. Thus, CV biomarkers are altered in patients with psoriasis. If the decrease in fetuin‐A as well as the increase in sCD40L can be proven in further studies, these biomarkers may help to characterize a subgroup of patients who are at risk to develop CVD and/or monitor the effect of therapeutic antipsoriatic strategies on concomitant diseases. This knowledge may be useful in the management of high‐need patients with psoriasis.     

DuCLOX-2/5 inhibition: a promising target for cancer chemoprevention

Cancer is a leading cause of death and major health concern worldwide. The animal and human studies support the presumption that inflammation directs the cancer initiation and progression. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are the key players in the inflammatory cascade contributing towards the angiogenesis, tumor cell invasiveness, and disruption in the pathways of cellular proliferation/apoptosis. Contemporary studies have particularized a promising role of COX-2 and 5-LOX inhibitors in cancer chemoprevention. The present review is a pursuit to define implications of dual COX-2 and 5-LOX (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention.     

Rifaximin,a pregnane X receptor (PXR) activator regulates apoptosis in a murine model of breast cancer

The present study was proposed to investigate the effect of rifaximin (RFX) on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. Animals were randomized and divided among four groups of six animals each. Group I (control 0.9% normal saline, 3 ml kg⁻¹, p.o.); Group II (toxic control, MNU 47 mg kg⁻¹, i.v.); Group III (RFX, 25 mg kg⁻¹, p.o.); Group IV (RFX, 50 mg kg⁻¹, p.o.). Toxicity was induced by single i.v. injection of MNU. MNU treatment was evident with increased alveolar bud count, differentiation score, up-regulated inflammatory enzyme markers (COX, LOX, NO and H₂S) and oxidative stress markers (TBAR''s, protein carbonyl, SOD, catalase and Ach). The mammary gland surface architecture was studied using SEM, carmine staining and H&E staining. The treatment with RFX elicited noticeable restoration of the overall histological architecture in the experimental animals similar to the control. In the MNU treated toxic group, the levels of oxidative stress markers significantly increased in comparison to the control, which was subsequently restored after RFX treatment. Furthermore, RFX up regulated the levels of caspase 3 and caspase 8, when compared to the MNU treated animals. MNU associated toxicity was also ascertained, when determined for UCHL-1, COX, NF-κBp65, BAD, and BCL-xl expression, while RFX demonstrated modulation of the same.

The present study was proposed to investigate the effect of rifaximin (RFX) on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats.     

A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain

Central nervous and hematopoietic systems share developmental features. We report that thrombopoietin (TPO), a stimulator of platelet formation, acts in the brain as a counterpart of erythropoietin (EPO), a hematopoietic growth factor with neuroprotective properties. TPO is most prominent in postnatal brain, whereas EPO is abundant in embryonic brain and decreases postnatally. Upon hypoxia, EPO and its receptor are rapidly reexpressed, whereas neuronal TPO and its receptor are down-regulated. Unexpectedly, TPO is strongly proapoptotic in the brain, causing death of newly generated neurons through the Ras-extracellular signal-regulated kinase 1/2 pathway. This effect is not only inhibited by EPO but also by neurotrophins. We suggest that the proapoptotic function of TPO helps to select for neurons that have acquired target-derived neurotrophic support.     

Surface antigen profiles of leukocytes and melanoma cells in lymph node metastases are associated with survival in AJCC stage III melanoma patients

There is an urgent need to identify more accurate prognostic biomarkers in melanoma patients, particularly in those with metastatic disease. This study aimed to identify melanoma and leukocyte surface antigens predictive of survival in a prospective series of AJCC stage IIIb/c melanoma patients (n = 29). Live cell suspensions were prepared from melanoma metastases within lymph nodes (LN). The suspensions were immuno-magnetically separated into CD45⁺ (leukocyte) and CD45^? (non-hematopoietic, enriched melanoma cell) fractions. Surface antigens on CD45^? and CD45⁺ cell populations were profiled using DotScan? microarrays (Medsaic Pty. Ltd.) and showed differential abundance levels for 52 and 78 antigens respectively. Associations of the surface profiles with clinicopathologic and outcome data (median follow-up 35.4 months post LN resection) were sought using univariate (log-rank test) and multivariate (Wald’s test; modelled with patient’s age, gender and AJCC staging at LN recurrence) survival models. CD9 (p = 0.036), CD39 (p = 0.004) and CD55 (p = 0.005) on CD45⁺ leukocytes were independently associated with distant metastasis-free survival using multivariate analysis. Leukocytes with high CD39 levels were also significantly associated with increased overall survival (OS) in multivariate analysis (p = 0.016). LNs containing leukocytes expressing CD11b (p = 0.025), CD49d (p = 0.043) and CD79b (p = 0.044) were associated with reduced OS on univariate analysis. For enriched melanoma cells (CD45^? cell populations), 11 surface antigens were significantly correlated with the disease-free interval (DFI) between diagnosis of culprit primary melanoma and LN metastasis resection. Nine antigens on CD45⁺ leukocytes also correlated with DFI. Following validation in independent datasets, surface markers identified here should enable more accurate determination of prognosis in stage III melanoma patients and provide better risk stratification of patients entering clinical trials.     

Value of upper gastrointestinal endoscopy for gastric cancer surveillance in patients with Lynch syndrome

In our study, we evaluated the effectiveness of upper gastrointestinal (GI) endoscopy as an instrument for early gastric cancer (GC) detection in Lynch syndrome (LS) patients by analyzing data from the registry of the German Consortium for Familial Intestinal Cancer. In a prospective, multicenter cohort study, 1128 out of 2009 registered individuals with confirmed LS underwent 5176 upper GI endoscopies. Compliance was good since 77.6% of upper GI endoscopies were completed within the recommended interval of 1 to 3 years. Forty‐nine GC events were observed in 47 patients. MLH1 (n = 21) and MSH2 (n = 24) mutations were the most prevalent. GCs in patients undergoing regular surveillance were diagnosed significantly more often in an early‐stage disease (UICC I) than GCs detected through symptoms (83% vs 25%; P = .0231). Thirty‐two (68%) patients had a negative family history of GC. The median age at diagnosis was 51 years (range 28‐66). Of all GC patients, 13 were diagnosed at an age younger than 45. Our study supports the recommendation of regular upper GI endoscopy surveillance for LS patients beginning no later than at the age of 30.