Genetic abnormalities and CNS tumors: report of two cases of ependymoma associated with Klinefelter’s Syndrome (KS)

Objects Genetic syndromes associated with ependymoma are uncommon, with the exception of NF2. We describe two cases of ependymoma presenting with Klinefelter’s Syndrome (KS) as co-morbid condition. Materials and methods The first patient was diagnosed for KS during pregnancy; he also presented a thyroid agenesis and a deficit of methyltetrahydrofolate reductase (MTHFR); at 30 months of age he was operated on for a grade II ependymoma of IV ventricle; after a multiple-stage surgery, he underwent oral chemotherapy and stereotactic radiotherapy, but after 15 months he presented a local recurrence and died. The second patient was diagnosed for KS at the age of 16 months; at 10 years of age, due to back pain, he underwent an MRI, which showed a cauda equine tumor. He underwent surgery and radiotherapy. Histology was of mixopapillary ependymoma. Conclusion In a review of literature, various neoplasms have been described in association with KS. To our knowledge, these are the first two cases reported of ependymoma associated to KS. A retrospective study of 44 monoinstitutional ependymoma cases demonstrated association with genetic syndromes in 22%.     

Reduced folate carrier polymorphism (80A-->G) and neural tube defects

Transport of folates in mammalian cells occurs by a carrier-mediated mechanism. The human folate carrier (RFC-1) gene has been isolated and characterized. Within this gene, a common polymorphism, 80A-->G, changing a histidine to an arginine in exon 2 (H27R), was recently identified. Defects in folate metabolism, such as defective carrier molecules, could be implicated in the etiology of neural tube defects (NTDs). In the present case-control study, we recruited 174 Italian probands with nonsyndromic NTD, 43 mothers, 53 fathers and 156 control individuals and evaluated the impact of RFC-1 variant on NTD risk. A statistically significant risk was calculated for the 80GG genotype of the NTD cases (OR=2.35; 95% CI 1.21-4.58) and mothers (OR=2.74; 95% CI 0.92-8.38). On the contrary, the heterozygous genotype of the mothers and both heterozygous and homozygous genotypes of the fathers did not seem to be significant NTD risk factors. Furthemore, according to the multifactorial inheritance of NTDs, we demonstrated that the combined genotypes for MTHFR 1298A-->C and RFC-1 80A-->G polymorphisms of cases resulted in greater NTD risk than heterozygosity or homozygosity for RFC-1 80A-->G variant alone. Conversely, our data provide no evidence for an association between NTD phenotype and combined MTHFR C677T/RFC-1 A80G genotypes. Moreover, here we describe the combinations of the two MTHFR polymorphic sites (677CT and 1298AC) with RFC-1 genotypes. We found that both patients and controls could have at most quadruple-mutation combinations. Interestingly, 27% (7/26) of the mothers and 18.75% (30/160) of the cases genotyped presented four mutant alleles in comparison with 8.5% (11/129) of the controls. Finally, the frequency of NTD cases and mothers carrying combined heterozygosity for the two MTHFR polymorphisms and RFC-1 80GG homozygosity (677CT/1298AC/80GG) (cases=11.3%; mothers 11.5%) was increased compared with controls (1.6%). Altogether, our findings support the hypothesis that RFC-1 A80G variant may contribute to NTD susceptibility in the Italian population.     

The effects of melatonin therapy on the development of scoliosis after pinealectomy in the chicken

The mechanism underlying the development of scoliosis after pinealectomy in young chickens is unknown. However, since the main product of the pineal gland is melatonin, melatonin remains an obvious focus in studies designed to discover this mechanism. One confounding factor is that serum melatonin levels are close to zero after pinealectomy but scoliosis does not develop in all chickens that have had this procedure. Therefore, the role of melatonin in the development of scoliosis in chickens after pinealectomy remains controversial. In the current investigation, two pilot studies demonstrated that a physiological therapeutic dose of melatonin (2.5 milligrams per kilogram of body weight) restored the circadian rhythm of melatonin, as measured by serum assay. In the main study, this dose was administered daily starting either immediately after the pinealectomy or two weeks after it, when scoliosis had developed. Scoliosis was assessed on weekly radiographs, and the Cobb angle was determined for all chickens in which scoliosis developed. Overall, scoliosis developed in only 56 percent (fifty) of the eighty-nine chickens that had had a pinealectomy; this rate was consistent throughout all experimental groups. Scoliosis did not develop in any of the control chickens, which did not have a pinealectomy. On the basis of the average Cobb angles in the chickens in which scoliosis had developed, it was determined that neither the prevalence nor the pattern of the scoliosis was affected by the therapy in any of the experimental groups. It was thus concluded that melatonin therapy after pinealectomy in young chickens has no effect on the development or progression of scoliosis. These results raise doubts regarding the role of melatonin in the development of scoliosis after pinealectomy in the young chicken.     

Preparation and local anaesthetic activity of benzotriazinone and benzoyltriazole derivatives

Two sets of benzotriazinone and benzoyltriazole derivatives were prepared and tested for local anaesthetic activity in comparison with lidocaine. Several of the prepared compounds exhibited a fairly good activity comparable or superior to that of lidocaine. The presence of a benzotriazinone or a benzoyltriazole moiety as an aromatic system was quite profitable for both the intensity and duration of activity. The acute toxicity in mice of the four most potent compounds of the series was also assessed. Compound 1b, which has an anaesthetic activity comparable to that of lidocaine, was also characterized by a more favourable therapeutic index. All compounds were tested in vitro to evaluate their negative chronotropic action in isolated rat right atria.     

Etiology of idiopathic scoliosis: current trends in research

Current population studies characterize idiopathic scoliosis as a single-gene disorder that follows the patterns of mendelian genetics, including variable penetrance and heterogeneity. The role of melatonin and calmodulin in the development of idiopathic scoliosis is likely secondary, with indirect effects on growth mechanisms. Reported abnormalities of connective tissue, skeletal muscle, platelets, the spinal column, and the rib cage are all thought to be secondary to the deformity itself. Although no consistent neurological abnormalities have been identified in patients with idiopathic scoliosis, it is possible that a defect in processing by the central nervous system affects the growing spine. The true etiology of idiopathic scoliosis remains unknown; however, it appears to be multifactorial.     

Neurologic toxicity of lidocaine during awake intubation in a patient with tongue base abscess. Case report

Lidocaine is commonly used for topical anesthesia of the upper airway in patient with anticipated difficult tracheal intubation undergoing awake fiberoptic intubation. Lidocaine toxicity is dose related and proportional to its plasma level. Although neurologic toxicity has been frequently observed with intravenous use, it has also been reported for topical use.     

Digital breast tomosynthesis and contrast‐enhanced dual‐energy digital mammography alone and in combination compared to 2D digital synthetized mammography and MR imaging in breast cancer detection and classification

To compare diagnostic performance of contrast‐enhanced dual‐energy digital mammography (CEDM) and digital breast tomosynthesis (DBT) alone and in combination compared to 2D digital mammography (MX) and dynamic contrast‐enhanced MRI (DCE‐MRI) in women with breast lesions. We enrolled 100 consecutive patients with breast lesions (BIRADS 3‐5 at imaging or clinically suspicious). CEDM, DBT, and DCE‐MRI 2D were acquired. Synthetized MX was obtained by DBT. A total of 134 lesions were investigated on 111 breasts of 100 enrolled patients: 53 were histopathologically proven as benign and 81 as malignant. Nonparametric statistics and receiver operating characteristic (ROC) curve were performed. Two‐dimensional synthetized MX showed an area under ROC curve (AUC) of 0.764 (sensitivity 65%, specificity 80%), while AUC was of 0.845 (sensitivity 80%, specificity 82%) for DBT, of 0.879 (sensitivity 82%, specificity 80%) for CEDM, and of 0.892 (sensitivity 91%, specificity 84%) for CE‐MRI. DCE‐MRI determined an AUC of 0.934 (sensitivity 96%, specificity 88%). Combined CEDM with DBT findings, we obtained an AUC of 0.890 (sensitivity 89%, specificity 74%). A difference statistically significant was observed only between DCE‐MRI and CEDM (P = .03). DBT, CEDM, CEDM combined to tomosynthesis, and DCE‐MRI had a high ability to identify multifocal and bilateral lesions with a detection rate of 77%, 85%, 91%, and 95% respectively, while 2D synthetized MX had a detection rate for multifocal lesions of 56%. DBT and CEDM have superior diagnostic accuracy of 2D synthetized MX to identify and classify breast lesions, and CEDM combined with DBT has better diagnostic performance compared with DBT alone. The best results in terms of diagnostic performance were obtained by DCE‐MRI. Dynamic information obtained by time‐intensity curve including entire phase of contrast agent uptake allows a better detection and classification of breast lesions.     

Nursing profession and nurses' contribution to nursing education as seen through students' eyes: A qualitative study

The behavior of clinical instructors, as observed by students, deeply influences their professional development. When instructors behave unprofessionally, they risk undermining the professional growth students gain from their clinical placement experience. Clinical instructors need to be aware of how their behavior can affect the students' learning process and the contributions they make to clinical nursing education. A qualitative study was performed to describe the nursing profession as perceived by students who observed their clinical instructors' behaviors during the clinical experience. In‐depth interviews of nursing students were conducted until data saturation was attained. Sixteen interviews were analyzed using an inductive content analysis methodology. The nursing profession was described by the participants through five themes as follows: the helping relationship, technical role, professional growth, working group, and contradictions and conflicts. Several examples of unprofessional behaviors on the part of the clinical instructors were reported by the respondents. The nursing profession, as perceived by nursing students, does not always reflect their expectations and their ideas related to professionalism. Universities and schools of nursing should ascertain that clinical instructors are prepared to educate students. Faculty should clearly state to students what they can expect from the clinical experience, namely, preparing students to face real working environments that do not always reflect educational philosophies.     

Cerebral small vessel disease affects white matter microstructure in mild cognitive impairment

Microstructural white matter deterioration is a frequent finding in mild cognitive impairment (MCI), potentially underlying default mode network (DMN) dysfunctioning. Thus far, microstructural damage in MCI has been attributed to Alzheimer's disease pathophysiology. A cerebrovascular role, in particular the role of cerebral small vessel disease (CSVD), received less interest. Here, we used diffusion tensor imaging (DTI) to examine the role of CSVD in microstructural deterioration within the normal appearing white matter (NAWM) in MCI. MCI patients were subdivided into those with (n = 20) and without (n = 31) macrostructural CSVD evidence on MRI. Using TBSS we performed microstructural integrity comparisons within the whole brain NAWM. Secondly, we segmented white matter tracts interconnecting DMN brain regions by means of automated tractography segmentation. We used NAWM DTI measures from these tracts as dependent variables in a stepwise‐linear regression analysis, with structural and demographical predictors. Our results indicated microstructural deterioration within the anterior corpus callosum, internal and external capsule and periventricular white matter in MCI patients with CSVD, while in MCI patients without CSVD, deterioration was restricted to the right perforant path, a tract along the hippocampus. Within the full cohort of MCI patients, microstructure within the NAWM of the DMN fiber tracts was affected by the presence of CSVD. Within the cingulum along the hippocampal cortex we found a relationship between microstructural integrity and ipsilateral hippocampal volume and the extent of white matter hyperintensity. In conclusion, we found evidence of CSVD‐related microstructural damage in fiber tracts subserving the DMN in MCI. Hum Brain Mapp 35:2836–2851, 2014. © 2013 Wiley Periodicals, Inc .     

In-vivo and in-vitro anti-inflammatory effect of Echinacea purpurea and Hypericum perforatum

Echinacea purpurea (L.) Moench and Hypericum perforatum (L.) were evaluated for their anti-inflammatory activity against carrageenan-induced paw oedema in mice. Each drug was administered orally to mice at 30 and 100 mg kg(-1), twice daily. Only the higher dose significantly inhibited, time dependently, the formation of oedema, evaluated as area under the curve (echinacea P < 0.01; hypericum P < 0.05). Western blot analysis showed that in-vivo treatment with these extracts could modulate lipopolysaccharide (LPS) and interferon-gamma induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in peritoneal macrophages. In particular, treatment with 100 mg kg(-1) hypericum inhibited both iNOS and COX-2 expression, whereas treatment with 100 mg kg(-1) echinacea down-regulated only COX-2 expression. The present study suggests that the anti-inflammatory effect of these extracts could be in part related to their modulation of COX-2 expression.