Genetic diversity of Mycobacterium tuberculosis in Madang, Papua New Guinea

Madang and surroundings, Papua New Guinea (PNG).

Comprehensive analysis of CpG island methylator phenotype (CIMP)-high, -low, and -negative colorectal cancers based on protein marker expression and molecular features

CpG island methylator phenotype (CIMP) is being investigated for its role in the molecular and prognostic classification of colorectal cancer patients but is also emerging as a factor with the potential to influence clinical decision-making. We report a comprehensive analysis of clinico-pathological and molecular features (KRAS, BRAF and microsatellite instability, MSI) as well as of selected tumour- and host-related protein markers characterizing CIMP-high (CIMP-H), -low, and -negative colorectal cancers. Immunohistochemical analysis for 48 protein markers and molecular analysis of CIMP (CIMP-H: ? 4/5 methylated genes), MSI (MSI-H: ? 2 instable genes), KRAS, and BRAF were performed on 337 colorectal cancers. Simple and multiple regression analysis and receiver operating characteristic (ROC) curve analysis were performed. CIMP-H was found in 24 cases (7.1%) and linked (p < 0.0001) to more proximal tumour location, BRAF mutation, MSI-H, MGMT methylation (p = 0.022), advanced pT classification (p = 0.03), mucinous histology (p = 0.069), and less frequent KRAS mutation (p = 0.067) compared to CIMP-low or -negative cases. Of the 48 protein markers, decreased levels of RKIP (p = 0.0056), EphB2 (p = 0.0045), CK20 (p = 0.002), and Cdx2 (p < 0.0001) and increased numbers of CD8+ intra-epithelial lymphocytes (p < 0.0001) were related to CIMP-H, independently of MSI status. In addition to the expected clinico-pathological and molecular associations, CIMP-H colorectal cancers are characterized by a loss of protein markers associated with differentiation, and metastasis suppression, and have increased CD8+ T-lymphocytes regardless of MSI status. In particular, Cdx2 loss seems to strongly predict CIMP-H in both microsatellite-stable (MSS) and MSI-H colorectal cancers. Cdx2 is proposed as a surrogate marker for CIMP-H.

The impact of CpG island methylator phenotype and microsatellite instability on tumour budding in colorectal cancer

In colorectal cancer, tumour budding, a process likened to epithelial mesenchymal transition, is an adverse prognostic factor which is rarely found in tumours with high-level microsatellite instability (MSI-H). Cases with MSI-H or high-level CpG island methylator phenotype (CIMP-H) have similar histomorphological features, yet seemingly opposite prognosis. We hypothesized that tumour budding is related to CIMP, thus partially explaining this prognostic difference.

[Fetal programming of cardiovascular disease: new causes and underlying mechanisms]

There exists an association between pathologic events occurring during early life and the development of cardiovascular disease in adulthood. For example, transient perinatal hypoxemia predisposes to exaggerated hypoxic pulmonary hypertension and preeclampsia predisposes the offspring to pulmonary and systemic endothelial dysfunction later in life. The latter finding offers a scientific basis for observations demonstrating an increased risk for premature cardiovascular morbidity in this population. Very recently, we showed that offspring of assisted reproductive technologies also display generalized vascular dysfunction and early arteriosclerosis. Studies in animal models have provided evidence that oxidative stress and/or epigenetic alterations play an important pathophysiological role in the fetal programming of cardiovascular disease.

Ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerve: accuracy of a selective new technique confirmed by anatomical dissection

BACKGROUND: Ilioinguinal and iliohypogastric nerve blocks may be used in the diagnosis of chronic groin pain or for analgesia for hernia repair. This study describes a new ultrasound-guided approach to these nerves and determines its accuracy using anatomical dissection control. METHODS: After having tested the new method in a pilot cadaver, 10 additional embalmed cadavers were used to perform 37 ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerve. After injection of 0.1 ml of dye the cadavers were dissected to evaluate needle position and colouring of the nerves. RESULTS: Thirty-three of the thirty-seven needle tips were located at the exact target point, in or directly at the ilioinguinal or iliohypogastric nerve. In all these cases the targeted nerve was coloured entirely. In two of the remaining four cases parts of the nerves were coloured. This corresponds to a simulated block success rate of 95%. In contrast to the standard 'blind' techniques of inguinal nerve blocks we visualized and targeted the nerves 5 cm cranial and posterior to the anterior superior iliac spine. The median diameters of the nerves measured by ultrasound were: ilioinguinal 3.0x1.6 mm, and iliohypogastric 2.9x1.6 mm. The median distance of the ilioinguinal nerve to the iliac bone was 6.0 mm and the distance between the two nerves was 10.4 mm. CONCLUSIONS: The anatomical dissections confirmed that our new ultrasound-guided approach to the ilioinguinal and iliohypogastric nerve is accurate. Ultrasound could become an attractive alternative to the 'blind' standard techniques of ilioinguinal and iliohypogastric nerve block in pain medicine and anaesthetic practice.