Somatostatin Receptor Localization of Pancreatic Endocrine Tumors

n = 39) than conventional imaging studies (MRI, n = 25; CT, n = 13); 23 of 24 patients had positive octreotide scintigraphy, 17 of 24 had positive MRI-scans, and 12 of 24 patients had positive CT scans. It was concluded that ¹¹¹ In-octreotide scintigraphy combined with conventional imaging improves the preoperative localization of presumably tumorous lesions in patients with gastroenterohepatic endocrine tumors.     

Thrombopoietin receptor agonist switch in children with persistent and chronic severe immune thrombocytopenia: A retrospective analysis in a large tertiary center

We retrospectively analyzed sequential therapy with romiplostim and eltrombopag in 23 children with immune thrombocytopenia: switching from romiplostim to eltrombopag (10 patients) or vice versa (13 patients). The median age of patients at enrollment in the study was 5.6 years (2‐15 years). Switching from romiplostim to eltrombopag was effective in eight (80%) patients, whereas switching from eltrombopag to romiplostim was effective in eight (62%) patients. The response rate was similar in patients failing the first thrombopoietin receptor agonist and those who had previous response. To date, all responders continue to maintain platelets over 50 × 10⁹/L at 13‐39 months after switching.     

Is proliferative colonic disease presentation changing?

AIM: To compare the site, age and gender of cases of colorectal cancer (CRC) and polyps in a single referral center in Rome, Italy, during two periods.METHODS: CRC data were collected from surgery/pathology registers, and polyp data from colonoscopy reports. Patients who met the criteria for familial adenomatous polyposis, hereditary non-polyposis colorectal cancer syndrome or inflammatory bowel disease were excluded from the study. Overlap of patients between the two groups (cancers and polyps) was carefully avoided. The χ² statistical test and a regression analysis were performed.RESULTS: Data from a total of 768 patients (352 and 416 patients, respectively, in periods A and B) who underwent surgery for cancer were collected. During the same time periods, a total of 1693 polyps were analyzed from 978 patients with complete colonoscopies (428 polyps from 273 patients during period A and 1265 polyps from 705 patients during period B). A proximal shift in cancer occurred during the latter years for both sexes, but particularly in males. Proximal cancer increased > 3-fold in period B compared to period A in males [odds ratio (OR) 3.31, 95%CI: 2.00-5.47; P < 0.0001). A similar proximal shift was observed for polyps, particularly in males (OR 1.87, 95%CI: 1.23-2.87; P < 0.0038), but also in females (OR 1.62, 95%CI: 0.96-2.73; P < 0.07).CONCLUSION: The prevalence of proximal proliferative colonic lesions seems to have increased over the last decade, particularly in males.     

Increased Contextual Fear Conditioning in iNOS Knockout Mice: Additional Evidence for the Involvement of Nitric Oxide in Stress-Related Disorders and Contribution of the Endocannabinoid System

Background:

Inducible or neuronal nitric oxide synthase gene deletion increases or decreases anxiety-like behavior in mice, respectively. Since nitric oxide and endocannabinoids interact to modulate defensive behavior, the former effect could involve a compensatory increase in basal brain nitric oxide synthase activity and/or changes in the endocannabinoid system. Thus, we investigated the expression and extinction of contextual fear conditioning of inducible nitric oxide knockout mice and possible involvement of endocannabinoids in these responses.

Methods:

We evaluated the effects of a preferential neuronal nitric oxide synthase inhibitor, 7-nitroindazol, nitric oxide synthase activity, and mRNA changes of nitrergic and endocannabinoid systems components in the medial prefrontal cortex and hippocampus of wild-type and knockout mice. The effects of URB597, an inhibitor of the fatty acid amide hydrolase enzyme, which metabolizes the endocannabinoid anandamide, WIN55,212-2, a nonselective cannabinoid agonist, and AM281, a selective CB1 antagonist, on contextual fear conditioning were also evaluated.

Results:

Contextual fear conditioning expression was similar in wild-type and knockout mice, but the latter presented extinction deficits and increased basal nitric oxide synthase activity in the medial prefrontal cortex. 7-Nitroindazol decreased fear expression and facilitated extinction in wild-type and knockout mice. URB597 decreased fear expression in wild-type and facilitated extinction in knockout mice, whereas WIN55,212-2 and AM281 increased it in wild-type mice. Nonconditioned knockout mice showed changes in the mRNA expression of nitrergic and endocannabinoid system components in the medial prefrontal cortex and hippocampus that were modified by fear conditioning.

Conclusion:

These data reinforce the involvement of the nitric oxide and endocannabinoids (anandamide) in stress-related disorders and point to a deregulation of the endocannabinoid system in situations where nitric oxide signaling is increased.     

Lack of alpha-1 integrin alters lesion morphology during pulmonary Mycobacterium tuberculosis infection

The hallmark of Mycobacterium tuberculosis infection is the granuloma, a highly dynamic immune structure that contains the bacilli during chronic infection. Here, we examined if alpha1beta1 integrin is required in the development and maintenance of the granulomatous structure during pulmonary infection using the alpha1 integrin knockout (alpha1-null) mouse. The alpha1beta1 integrin is expressed on activated macrophages and T cells, and interacts with collagen molecules in the extracellular matrix (ECM), and thus may play a role in the granulomatous process. Following pulmonary infection with virulent M. tuberculosis, lungs of alpha1-null infected mice had striking differences in granuloma structure, as well as distinct and markedly thickened alveolar septae. By day 180, there were regions of cell death within granulomatous lesions, characterized by cellular debris in these mice. To determine if this molecule was necessary for T cell trafficking within the lungs, the expression of CD4, CD44 and CD62L was monitored. The number of activated and IFN-gamma-producing CD4(+) T cells increased in the lungs of alpha1-null mice during the chronic phase of infection, although they had decreased concentrations of TNF-alpha and MMP-9. These results suggest that while alpha1beta1 integrin is not required for trafficking or maintenance of T cells in M. tuberculosis infected lungs, it does play a role in granuloma structure and integrity during the chronic phase of infection.     

MEF2C deletions and mutations versus duplications: A clinical comparison

5q14.3 deletions including the MEF2C gene have been identified to date using genomic arrays in patients with severe developmental delay or intellectual disability, stereotypic behavior, epilepsy, cerebral malformations and a facial gestalt not really distinctive though characterized by broad and/or high, bulging forehead, upslanting palpebral fissures, flat nasal root and bridge, small, upturned nose, hypotonic small mouth resulting in cupid bow/tented upper lip. MEF2C mutations have been also identified in patients with overlapping phenotype so that it is considered the gene responsible for the 5q14.3 deletion syndrome. To date, one single duplication including MEF2C has been reported in a patient with intellectual disability but its clinical significance remains uncertain also because of the large size of the imbalance. Here we present two further patients with 5q14.3 duplications including MEF2C. Their phenotype indeed suggest the pathogenic effect of the MEF2C duplication although other duplicated genes also brain expressed might contribute to the clinical features. In none of them a clear-cut syndrome can be identified. A comparison between MEF2C deleted/mutated and duplicated patients is also presented.