Frequency of selected thrombophilias in women with placental abruption

OBJECTIVE: There is a growing view that inherited or acquired thrombophilia may predispose a woman towards an adverse pregnancy outcome. The aim of this study was to investigate whether risk factors for placental abruption because of such thrombophilias (such as carriership of factor V Leiden (FVL), prothrombin G20210A gene mutation and homozygous MTHFR C677T) might be used as a predictor for placental abruption. METHODS: A retrospective case-control study conducted at the University Hospital, Palacky University, Olomouc, Czech Republic. One hundred and eighty women with placental abruption out of 20,175 deliveries (0.79%) were compared to 196 unselected gravidae. A detailed medical history was taken with special reference to factors related to hypercoagulation and blood was drawn for polymerase chain reaction analysis. The prevalence of FVL, prothrombin G20210A and MTHFR C677T was related to placental abruption. RESULTS: The heterozygous form of FVL was present in 20of 142 cases (14.1%) in the placental abruption group, compared to ten of 196 (5.1%) in the control group (odds ratio 3.0, 95% confidence interval 1.4-6.7). CONCLUSIONS: We found that factor V Leiden is a significant risk factor for placental abruption.     

The acute nootropic effects of Ginkgo biloba in healthy older human subjects: a preliminary investigation

Ginkgo biloba has been shown to have chronic memory enhancing effects in healthy subjects and patients with dementia. There is limited research on the acute nootropic effects of Ginkgo biloba in humans. The current study aimed to examine the acute effects of Ginkgo biloba (120 mg) on memory functioning in healthy older volunteers using the cognitive drug research (CDR) battery of memory tests and the Rey auditory verbal learning task (AVLT). The study was a double-blind placebo-controlled design, with each participant tested under both placebo and Ginkgo biloba treatment conditions. Testing was conducted pre- and 90 min post-drug administration for each treatment condition. Treatment conditions were separated by a 7 day wash out period. No acute effects of Ginkgo biloba were found for any of the memory tests examined. The findings suggest that 120 mg of Ginkgo biloba has no acute nootropic effects in healthy older humans.     

Prediction of fusion and importance of radiological variables for the outcome of anterior cervical decompression and fusion

In a prospective randomised study with a 2-year follow-up, 103 patients were randomised to anterior cervical decompression and fusion (ACDF) with a cervical carbon-fibre intervertebral fusion cage (CIFC) or the Cloward procedure (CP). The purpose of the present study was to report predictors for fusion and also to investigate the importance of radiological variables for the clinical outcome. Gender, age, smoking habits, disc height, segmental kyphosis and type of surgical procedure were used as independent (before surgery) variables in a multiple regression model. Male gender, one-level surgery and CP treatment were significant predictors of fusion and explained 14% of the variability of fusion status at follow-up. Number of levels operated on, however, did not influence the clinical outcome. Fifty-two per cent of the women and 17% of the men in the CIFC group, and 25% of the women and 8% of the men in the CP group, had pseudarthrosis. Although patients with a healed fusion had significantly less pain intensity than patients with pseudarthrosis, radiological variables explained only 4% of the variability of pain at follow-up. Apart from a significant correlation between preoperative kyphosis and neck disability index at follow-up, no significant correlation between either postoperative kyphosis or preoperative or postoperative disc height and clinical outcome was found. Neither degree of segmental kyphosis nor disc height was different between patients with healed fusion and pseudarthrosis. One can conclude that male gender and type of surgery were significant predictors for a healed fusion and that pseudarthrosis affected outcome. In contrast to the commonly held view based mainly on theoretical considerations, no effect on clinical outcome could be demonstrated for segmental kyphosis and disc height at follow-up. Overall, the study shows that the importance of radiological factors as predictors for fusion as well as clinical outcome is limited.     

Induction of aryl hydrocarbon receptor-mediated and estrogen receptor-mediated activities, and modulation of cell proliferation by dinaphthofurans

A group of heterocyclic aromatic compounds, dinaphthofurans (DNFs), recently have been identified as potentially significant contaminants in freshwater sediments. In the present study, a battery of in vitro assays was used for detection of toxic effects of DNFs that are potentially associated with endocrine disruption and tumor promotion. Dinaphthofurans were found to act as relatively potent inducers of aryl hydrocarbon receptor (AhR)-mediated activity in the chemical-activated luciferase reporter gene expression DR-CALUX assay. The relative AhR-inducing potencies of DNFs were similar or even higher than relative potencies of unsubstituted polycyclic aromatic hydrocarbons (PAHs), with dinaphtho[1,2-b;2'3'-d]furan being the most potent AhR agonist. Two compounds, dinaphtho[2,1-b;2'3'-d]furan and dinaphtho[1,2-b;1'2'-d]furan, induced estrogen receptor (ER)-mediated activity in the estrogen receptor-mediated CALUX (the ER-CALUX) assay. Two types of potential tumor-promoting effects of DNFs were investigated, using in vitro bioassays for detection of inhibition of gap-junctional intercellular communication and detection of a release from contact inhibition. Although the acute inhibition of gap-junctional intercellular communication was not observed, all six tested DNFs were able to release rat liver epithelial WB-F344 cells from contact inhibition at concentrations as low as 100 nM. In summary, the present study indicated that DNFs can exert multiple biological effects in vitro, including induction of the AhR-mediated activity, release of cells from contact inhibition, and induction of ER-mediated activity.     

Inhibition of gap-junctional intercellular communication by environmentally occurring polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are a broad class of ubiquitous environmental pollutants with known or suspected carcinogenic properties. Tumor promotion is a cell-proliferative step of cancer that requires the removal of cells from growth suppression via the inhibition of gap-junctional intercellular communication (GJIC). Inhibition of GJIC measured with an in vitro WB-F344 rat liver epithelial cell system was used to assess the relative potencies of 13 PAHs suggested by the U.S. Environmental Protection Agency (EPA) as the principal contaminants and 22 other PAHs, most of them identified in environmental samples. Maximal inhibition of GJIC was detected after 30 min of exposure, followed by a recovery in intercellular communication after an additional 30 min of exposure, suggesting a transient character of inhibition. Although microM concentrations of PAHs were required to reach the inhibition level equal to the model tumor promoter phorbol 12-myristate 13-acetate (IC50 = 8 nM), 12 of the PAHs under study were found to be strong inhibitors of GJIC (strongest effects were observed with fluoranthene, picene, 5-methylchrysene and nine additional PAHs). The other nine PAHs, including benzo[a]pyrene, inhibited GJIC only up to 50-75% of the control level. Interestingly, several high molecular weight PAHs with known strong carcinogenic properties possessed only weak (dibenzopyrenes) or no inhibition potency (dibenzofluoranthenes, naphtho[2,3-a]pyrene and benzo[a]perylene). Based on the IC50 values related to the reference PAH benzo[a]pyrene, we suggested arbitrary values of inhibition equivalency factors (GJIC-IEFs) ranging from 0 (noninhibiting PAHs) to 10.0 (strongest inhibitors), suitable for the purposes of environmental risk assessment.     

Salvage treatment with upfront melphalan 100 mg/m2 and consolidation with novel drugs for fulminant progression of multiple myeloma

Patients (pts) with fulminant progression (FPG) of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) have poor prognosis. Pancytopenia, extramedullary disease, and/or renal impairment are often present, and treatment options are limited. We have retrospectively evaluated 31 pts with FPG of MM after ASCT who were treated upfront salvage therapy with melphalan 100 mg/m² (MEL 100) followed by PBSC support and consolidation therapy using regimens containing thalidomide (n?=?16) or bortezomib (n?=?15). The overall response rate (ORR) was 58% (18/31). After MEL 100, one patient achieved complete remission (3%), 26% of pts very good partial remission, 29% of pts partial remission, and 42% of pts stable disease. Progression within 3 months after MEL 100 occurred in 35% of pts. The median follow-up from MEL 100 was 8 months. The median TTP was 5 months (range, 2–15 months), and the median OS was 8 months (range, 3–23 months). There were no treatment-related deaths. In fulminant progression of MM, upfront MEL 100 is a safe salvage regimen with good response rate (ORR, 58%). Treatment with upfront MEL 100 followed by a thalidomide- or bortezomib-based regimen can prolong overall survival to more than 12 months in 33% of pts with fulminant progression of MM.     

Focal nodular hyperplasia: spoke-wheel arterial pattern and other signs on dynamic contrast-enhanced ultrasonography

OBJECTIVE: To evaluate the prevalence of spoke-wheel pattern and typical symptoms of focal nodular hyperplasia (FNH) by means of dynamic contrast-enhanced ultrasonography (CEUS) in relation to lesion size. METHODS: Twenty-eight patients were included in the trial, in whom, based on the CEUS, we raised suspicion of hypervascularized liver lesion; there were 30 lesions altogether. The final diagnosis of FNH was verified by means of CT, MRI or lesion biopsy. Majority of patients (26) were females, compared to 2 male, with average age of 33.3 years. Average lesion size was 45.6 mm. Besides the ultrasound examination, we used also "blood pool" ultrasound contrast agent of second generation, sulphur hexafluoride (BR1); we evaluated enhancement of the lesion until the late stage-within 5 min from application. RESULTS: In lesions larger than 3 cm (n=20), stellate vascular enhancement was found in 19 cases (95.0%) early in arterial phase. As for lesions smaller than 3 cm (n=10), spoke-wheel pattern was observed only in 3 cases (30%) and lesions smaller than 2 cm practically did not show this phenomenon at all (n=1; 17%). Generally, symptom of spoke-wheel pattern was observed in 22 cases, i.e. in 73.3%. In total, central scar was present in 63.3% (n=19) of cases. In lesions larger than 3 cm, it was present in 85.0% (n=17), in lesions smaller than 3 cm in 20% (n=2). CONCLUSION: Contrast-enhanced ultrasonography can be the final diagnostic method for FNH larger than 3 cm which has typical spoke-wheel vessel structure on CEUS. If this phenomenon is not present and the central scar is not visible, specific diagnosis of FNH cannot be based solely on CEUS findings.