Intracranial pressure in patients with papilloedema.

OBJECTIVES: Papilloedema is a clinical manifestation of chronically raised intracranial pressure (ICP), often seen in idiopathic intracranial hypertension (IIH). However, the extent of intracranial hypertension required to produce papilloedema is not known. We compare ICP values in IIH patients who developed papilloedema and those who did not. We aim to identify a pathological ICP threshold predictive of the development of papilloedema in IIH patients. MATERIALS AND METHODS: Single-centre cohort of IIH patients (2006-2016) who underwent 24-hour ICP monitoring (ICPM) and ophthalmology assessments, prior to intervention. Papilloedema was graded according to the Frisén scale. An unpaired t-test compared 24-hour ICPM between papilloedema and no-papilloedema groups. Fisher's exact test was used to determine predictive value of ICP. RESULTS: Thirty-six patients with IIH (35 F: 1M), mean age 32.5 ± 9.49 years (mean ± SD) were included. Patients with papilloedema had a mean median 24-hour ICP of 10.4 ± 5.32 mm Hg (n = 25), significantly higher than the group without papilloedema 6.31 ± 3.30 mm Hg (n = 11) (P < .05). The papilloedema group were exposed to higher pressures (10 mm Hg) for 30 minutes or more. Using 24-hour median ICP of 10 mm Hg as a minimum cut-off predictive value gives a specificity = 91%, sensitivity = 48%, PPV = 92% and NPV = 44% of detecting papilloedema. CONCLUSIONS: A 24-hour ICP of 10 mmHg or more is a good predictor for papilloedema and reflects a pathological threshold. The range varied widely suggesting papilloedema can occur at even lower pressures. These results are consistent with emerging evidence suggest that pathologically "high" 24 hours ICP is lower than previously quoted.

A cryptic balanced translocation (5;17), a puzzle revealed through a critical evaluation of the pedigree and a FISH focused on candidate loci suggested by the phenotype.

We report a case of a woman with a cryptic balanced translocation between chromosomes 5 and 17, suspected during genetic counseling. The woman had a history of previous fetal losses attributed to lissencephaly and intra uterine growth retardation (IUGR) and a daughter with dysmorphic features and mental retardation, previously attributed to a small deletion 5pter, detected years ago by a first generation CGH-array. This peculiar combination of personal and family history suggested the opportunity to carry out a FISH approach, focusing on chromosomes 5 and 17, based on the idea that a malsegregation secondary to a balanced translocation, might have escaped the first CGH array. This approach allowed the identification of a balanced translocation in the mother, FISH in the affected child confirmed the partial 5p deletion predicted by the previous CGH array and identified a new 17p duplication that had not been detected before. The described translocation opens the possibility of alternative imbalances that were probably responsible for previous fetal losses. The imbalances were confirmed by a new high resolution SNP array. We conclude that despite the availability of highly effective and sensitive genomic approaches a careful evaluation of medical history is highly recommended since it can suggest clinical hypothesis that can be confirmed by more classical and molecular cytogenetic based approaches.

Sgk1 enhances RANBP1 transcript levels and decreases taxol sensitivity in RKO colon carcinoma cells.

The serum- and glucocorticoid-regulated kinase (Sgk1) is essential for hormonal regulation of epithelial sodium channel-mediated sodium transport and is involved in the transduction of growth factor-dependent cell survival and proliferation signals. Growing evidence now points to Sgk1 as a key element in the development and/or progression of human cancer. To gain insight into the mechanisms through which Sgk1 regulates cell proliferation, we adopted a proteomic approach to identify up- or downregulated proteins after Sgk1-specific RNA silencing. Among several proteins, the abundance of which was found to be up- or downregulated upon Sgk1 silencing, we focused our attention of RAN-binding protein 1 (RANBP1), a major effector of the GTPase RAN. We report that Sgk1-dependent regulation of RANBP1 has functional consequences on both mitotic microtubule activity and taxol sensitivity of cancer cells.