Karyotypic evolution pathways in medulloblastoma/primitive neuroectodermal tumor determined with a combination of spectral karyotyping, G-banding, and fluorescence in situ hybridization

Medulloblastomas (MBs) or primitive neuroectodermal tumors (PNETs) represent 15%-30% of pediatric brain tumors and are the most common brain tumors in children; they are rare in adults. Classification of these tumors is based on tissue morphology and is often controversial and problematic. Karyotypic analysis of these tumors using conventional cytogenetic methods is often a difficult process that may be hindered by a limited number of metaphase cells and poor chromosome morphology, often leading to only partial characterization of the chromosomal abnormalities. We investigated three primary human tumors and four cell lines (CHO-707, DAOY, D-341, and PFSK) utilizing a combination of conventional G-banding, spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH) techniques. A high level of intratumoral heterogeneity was seen, with multiple numerical and structural chromosomal aberrations. The chromosomes most frequently involved in structural aberrations were chromosomes 1 (14 rearrangements), 7 (9 rearrangements), and 21 (9 rearrangements). The chromosomes most frequently involved in numerical aberrations were chromosomes 1, 12, and 13 (four cases) and chromosomes 14, 17, 19, 21, 22, and X (three cases). Numerous aberrant chromosomes were characterized only with the SKY analysis, and based on these findings multiple clones were identified, facilitating analysis of karyotypic evolution. The most frequent evolution mechanism was via polyploidization, followed by acquisition of additional numerical or structural aberrations (or both); however, the results showed that the karyotypic evolution process in these tumors is typically divergent and complex.     

Comparison of magnesium status using X-ray dispersion analysis following magnesium oxide and magnesium citrate treatment of healthy subjects

The magnesium content in food consumed in the Western world is steadily decreasing. Hypomagnesemia is associated with increased incidence of diabetes mellitus, metabolic syndrome, all-cause and coronary artery disease mortality. We investigated the impact of supplemental oral magnesium citrate versus magnesium oxide on intracellular magnesium levels ([Mg2+]i) and platelet function in healthy subjects with no apparent heart disease. In a randomized, prospective, double-blind, crossover study, 41 (20 women) healthy volunteers [mean age 53±8 (range 31-75) years] received either magnesium oxide monohydrate tablets (520 mg/day of elemental magnesium) or magnesium citrate tablets (295.8 mg/day of elemental magnesium) for one month (phase 1), followed by a four-week wash-out period, and then crossover treatment for one month (phase 2). [Mg2+]i was assessed from sublingual cells through x-ray dispersion (normal values 37.9±4.0 mEq/L), serum magnesium levels, platelet aggregation, and quality-of-life questionnaires were assessed before and after each phase. Oral magnesium oxide, rather than magnesium citrate, significantly increased [Mg2+]i (34.4±3 versus 36.3±2 mEq/L, p<0.001 and 34.7±2 versus 35.4±2 mEq/L, p=0.097; respectively), reduced total cholesterol (201±37 versus 186±27 mg/dL, p=0.016 and 187±28 versus 187±25 mg/dL, p=0.978; respectively) and low-density lipoprotein (LDL) cholesterol (128±22 versus 120±25 mg/dL, p=0.042 and 120±23 versus 121±22 mg/dL, p=0.622; respectively). Noteworthy is that both treatments significantly reduced epinephrine-induced platelet aggregation (78.9±16% versus 71.7±23%, p=0.013 and 81.3±15% versus 73.3±23%, p=0.036; respectively). Thus, oral magnesium oxide treatment significantly improved [Mg2+]i, total and LDL cholesterol compared with magnesium citrate, while both treatments similarly inhibited platelet aggregation in healthy subjects with no apparent heart disease.     

The association between previous single first trimester abortion and pregnancy outcome in nulliparous women

Objective: To determine the association between single previous abortion and pregnancy outcome in nulliparous women.

Methods: A retrospective cohort study of all nulliparous women who delivered in a university-affiliated tertiary hospital (2009–2014). Pregnancy outcome of women with single previous first trimester abortion (study group) was compared to those of primigravida (control group).

Results: Of the 44?371 deliveries during the study period, 14?498 (32.6%) were of nulliparous women, of them 1501 (10.3%) had single previous abortion (<13 weeks). Except for a higher rate of diabetes mellitus in the study group (6.1 versus 4.4%, p?=?0.003), no differences were found between the groups regarding pregnancy complications. In multivariate analysis, previous single abortion was independently associated with induction of labor (OR?=?1.31, 95%C.I 1.04–1.63, p?=?0.01), cesarean section (OR?=?1.38, 95%C.I 1.18–1.60, p?<?0.001) and retained placenta (OR?=?1.29, 95%C.I 1.03–1.61, p?=?0.02). Among nulliparous women with previous single abortion no difference in pregnancy outcome was observed between those with previous induced termination of pregnancy and spontaneous abortion, except for increased risk for retained placenta in those with previous spontaneous abortion.

Conclusion: Single early previous abortion in nulliparous women was associated with higher rate of induction of labor, cesarean section and retained placenta compared to primigravida women.     

Statins,aspirin and risk of thromboembolic events in ovarian cancer patients

Objectives

Studies suggest that statins and low dose aspirin reduce risk of VTEs in the general population. We aimed to study the effect of these drugs on the incidence of VTEs in patients with ovarian cancer.

Methods

Patients diagnosed with ovarian cancer between 2000 and 2011 were identified through the Clalit Health Services (CHS) chronic disease registry. Data were extracted from CHS database and from computerized pharmacy records. Use of medications was analyzed as a time dependent covariate in a Cox regression model.

Results

Of 1746 patients 175 (10%) had a VTE during a median follow up of 3.13 years. 83 patients (5.6%) had a VTE within 2 years of diagnosis of ovarian cancer. Use of chemotherapy and stage 3 and 4 at presentation were associated with an increased risk for VTEs.Statins were used by 43.5% of the patients, and 32.3% used aspirin. Aspirin use was associated with a marginally significant reduction in incidence of VTEs within 2 years of diagnosis, HR 0.423 (95% CI 0.182–1.012, p-value 0.053). Statin use was not associated with risk of VTEs.

Conclusion

This is the first study looking at the effect of statins and aspirin on the incidence of VTEs in ovarian cancer patients. In our cohort, statins did not decrease the risk for a VTE and aspirin use was associated with a reduced risk which was marginally significant. Our results might be explained by use of low potency statins and by alternate mechanisms for VTE formation in cancer patients.     

The presurgical workup before third molar surgery: how much is enough?

PURPOSE: We sought to assess the indications for patient referral for computed tomography (CT) scan before third molar extraction. The influence of the data obtained from the CT scans on the surgical outcome and morbidity was also evaluated. PATIENTS AND METHODS: There were 189 patients in the study (120 females and 69 males). Sixty-five patients were referred to receive CT and formed the study group. The remaining patients were included in the control group. RESULTS: There were no statistically significant differences between the groups with regard to demographic data and tooth and root angulations. Indications for tooth extraction such as pain, swelling, pericoronitis, caries, endodontic problems, pathology, and prosthetic considerations were similar. The proximity of the tooth root to the inferior alveolar canal was the only statistically significant difference between the 2 groups (P <.001). The treatment plan outcomes for extraction, surgical extraction, and follow-up were comparable. The surgeon changed the initial decision from "surgical extraction" to "follow-up" in only 1 case after CT scan. CONCLUSIONS: Within the limits of the present study, it can be concluded that the main reason for CT scan referral is the proximity of the third molar root to the inferior alveolar canal (<1 mm). The data obtained from the CT scan had minimal effect on the final surgical outcome. The routine use of CT scan in cases of third molar extractions cannot be recommended.