Agenesis of the corpus callosum associated with narcolepsy-cataplexy

We describe a 24-year-old man with episodes of intense desire to sleep for periods ranging from 2min to 3h, episodes of generalized weakness and inability to speak without alteration of consciousness, frequent hypnagogic hallucinations during sleep and occasionally transient paralysis of limbs upon awakening. Brain MRI demonstrated elevation of the third ventricle, a characteristic lack of depiction of the corpus callosum and extension of the bihemispheric fissure to the third ventricle. We assume that structural changes of the base of frontal lobes, diencephalon and brainstem, can be accountable for symptomatic narcolepsy and cataplexy.     

In vitro and in vivo antitumor activity of platinum(II) complexes with thiosemicarbazones derived from 2-formyl and 2-acetyl pyridine and containing ring incorporated at N(4)-position: synthesis, spectroscopic study and crystal structure of platinum(II) complexes with thiosemicarbazones, potential anticancer agents

Reactions of thiosemicarbazones of 2-formyl and 2-acetyl pyridine and containing an azepane ring (hexamethyleneiminyl ring) incorporated at N(4)-position, HL(1) (1) and HL(2) (2) with platinum(II) afforded the complexes, [Pt(L(1))Cl] (3) and [Pt(L(2))Cl] (4). Characterization of the compounds was accomplished by means of elemental analysis and spectroscopic techniques NMR, UV-vis and IR spectroscopy. The single-crystal X-ray structure of complex [Pt(L(2))Cl] (4) shows that the ligand monoanion coordinates in a planar conformation to the metal via the pyridyl N atom, the imine-N atom, and thiolato S-atom. Compounds 1-4 have been evaluated for antiproliferative activity in vitro against three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). Ligand 2 exhibited high activity as anticancer agent against all four cancer cell lines, while ligand 1 exhibited selectivity against MCF-7, L-929 cell lines and complex 4 against A-549, T-24 cancer cell lines. Also, the acute toxicity and antitumor activity were evaluated on leukemia P388-bearing mice. Complex 3 afforded five to six cures against leukemia P388. The in vivo results of the antitumor activity show the two platinum complexes as very effective chemotherapeutic antileukemic agents.     

Acute Tc-99m DMSA scan for identifying dilating vesicoureteral reflux in children: a meta-analysis

Controversy exists regarding the type and/or sequence of imaging studies needed during the first febrile urinary tract infection (UTI) in young children. Several investigators have claimed that because acute-phase Tc-99m dimercaptosuccinic acid (DMSA) renal-scan results are abnormal in the presence of dilating vesicoureteral reflux, a normal DMSA-scan result makes voiding cystourethrography (VCUG) unnecessary in the primary examination of infants with UTI. To evaluate the accuracy of acute-phase DMSA scanning in identifying dilating (grades III through V) vesicoureteral reflux documented by VCUG in children with a first febrile UTI, we performed a meta-analysis of the accuracy of diagnostic tests as reported from relevant studies identified through the PubMed and Scopus databases. Patient-based and renal unit-based analyses were performed. Overall, 13 cohort studies were identified. Nine studies involved patients younger than 2 years, 3 involved children aged 16 years or younger, and 1 involved exclusively neonates. Girls constituted 22% to 85% of the involved children. Pooled (95% confidence intervals) sensitivity and specificity rates of DMSA scanning were 79% and 53%, respectively, for the patient-based analysis (8 studies) and 60% and 65% for the renal unit-based analysis (5 studies). The respective areas under the hierarchical summary receiver operating curves were 0.71 and 0.67. Marked statistical heterogeneity was observed in both analyses, as indicated by I(2) test values of 91% and 87%, respectively. Acute-phase DMSA renal scanning cannot be recommended as replacement for VCUG in the evaluation of young children with a first febrile UTI.     

Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC bead

PURPOSE: To examine the results of segmental transcatheter arterial chemoembolization with doxorubicin-loaded DC Bead in the treatment of hepatocellular carcinoma (HCC) in non-surgical candidates. MATERIAL AND METHODS: Seventy-one patients (60% men; 11% women; mean age 63; range 46-71 years) with documented HCC of 3-10 cm in diameter (mean 6.2) were enrolled prospectively in the study. All patients had cirrhosis-related HCC that was developed on an underlying controlled hepatitis infection. Only patients with compensated cirrhosis--Child A or B--were included in this study. RESULTS: Overall complete response (CR) according to EASL on an intention to treat basis was seen in 11 patients who developed complete necrosis (15.5%). Objective response (OR) ranged from 66.2% to 85.5% across the four treatments. Survival at 12 months was 97.05%. Sustained CR was observed in 11 (16.1%), and OR in 49 (72%). Sustained partial response was seen in 49 patients (72.05%). Survival at 18 months was 94.1%. At 24 months follow-up survival was 91.1%. Sustained OR was seen in 45 patients (66.2%) while sustained CR was 16.1% (11/68). At 30 months survival was 88.2%. One patient with CR developed multifocal HCC in areas that most likely were not embolized during the previous embolization sessions. In this patient recurrence-free survival was 28 months. Alpha Fetroprotein levels decreased significantly in measurements 1 month post each procedure (p < 0.001). Bilirubin, gamma-GT, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (ALP) showed only transient increases observed during the study period. Severe procedure-related complications were seen in 4.2% (cholecystitis: n = 1; liver abscess: n = 1; pleural effusion: n = 1). Post Embolization Syndrome (PES) was observed in all patients. CONCLUSION: Transcatheter arterial chemoembolization with DC Bead is an effective and safe procedure in the treatment of HCC patients not eligible for curative treatments with high rates of response and high rates of mid term survival.     

Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior

The accurate execution of DNA replication requires a strict control of the replication licensing factors hCdt1 and hCdc6. The role of these key replication molecules in carcinogenesis has not been clarified. To examine how early during cancer development deregulation of these factors occurs, we investigated their status in epithelial lesions covering progressive stages of hyperplasia, dysplasia, and full malignancy, mostly from the same patients. Abnormal accumulation of both proteins occurred early from the stage of dysplasia. A frequent cause of unregulated hCdc6 and hCdt1 expression was gene amplification, suggesting that these components can play a role per se in cancer development. Overexpression of hCdt1 and hCdc6 promoted rereplication and generated a DNA damage response, which activated the antitumor barriers of senescence and apoptosis. Generating an inducible hCdt1 cellular system, we observed that continuous stimulus by deregulated hCdt1 led to abrogation of the antitumor barriers and resulted in the selection of clones with more aggressive properties. In addition, stable expression of hCdc6 and hCdt1 in premalignant papilloma cells led to transformation of the cells that produced tumors upon injection into nude mice depicting the oncogenic potential of their deregulation.