Distant metastases in meningioma: an underestimated problem

Meningioma is a common intracranial neoplasm derived from meningothelial cells. Meningiomas are associated with a benign clinical course. However, malignant behaviour such as metastatic disease has been also described. Our aim was to analyze the metastatic pattern taking tumor grading into consideration, and to determine clinical signs of distant metastases in meningiomas. In this systematic review PubMed database was screened for distant meningioma metastases from 1990 to 2012. 95 articles were identified. Only cases with metastasized meningiomas were included in the analysis. Our analysis comprised 115 cases with 164 metastatic lesions. Primary tumors were in 33.9 % grade 1, 20.9 % grade 2, and 40 % grade 3. In 5.2 % the grade was not reported. In 93 % meningiomas were diagnosed and resected before distant metastases occurred. In 6.1 % metastases were identified simultaneously with primary tumors and in 0.9 % metastases were identified before the primary tumor was found. The metastatic lesions were localized most frequently in the lung (37.2 %), bones (16.5 %), intraspinally (15.2 %), and in the liver (9.2 %). Other locations were rarer. The size of the metastases varied from 0.6 to 28 cm (median size, 3 cm). There were no significant differences between sizes of the identified metastases in relation to tumor grading. 50.4 % of distant metastases were clinically manifest and 31.3 % were identified incidentally. In 18.3 % clinical signs were missing. In our review 31.3 % of metastatic meningiomas were found to be clinically silent. The prevalence of metastases in meningioma may be underreported.     

Tuberculous and Non-Tuberculous Granulomatous Lymphadenitis in Patients Receiving Imatinib Mesylate (Glivec) for Metastatic Gastrointestinal Stromal Tumor

Background

Imatinib mesylate (IM) is the standard treatment for BCR-ABL-positive chronic myelogenous leukemia (CML) and is the first-line adjuvant and palliative treatment for metastatic and inoperable gastrointestinal stromal tumor (GIST). IM is not known to be associated with an increased risk for development of granulomatous diseases.

Methods

We describe our experience with 2 patients (42 and 62 years of age) who developed granulomatous disease during IM treatment for metastatic GIST.

Results

Mean duration of IM treatment was 12 (range 8–16) months. Enlarged lymph nodes with increased metabolism on FDG-PET-CT examination were detected and resected. Affected sites were supraclavicular (1) and subcarinal/mediastinal (1) lymph nodes. Histological examination revealed caseating and non-caseating granulomas suggestive of tuberculosis and sarcoidosis, respectively. Mycobacterium tuberculosis was detected by PCR in lymph nodes of 1 patient who was then successfully treated by anti-tuberculous agents. The other patient had negative sputum test for acid-fast bacilli and PCR-DNA-analysis was negative for M. tuberculosis and other mycobacteria. He received no anti-tuberculous therapy and had no evidence of progressive lymphadenopathy or new lung lesions during follow-up.

Conclusion

Our observations underline the necessity to obtain biopsy material from enlarged or metabolically active lymph nodes developing during IM treatment for timely diagnosis and appropriate treatment of these rare complications. Follow-up without treatment is safe for patients without detectable microorganisms by sputum examination and PCR.Key words: Gastrointestinal stromal tumor, Imatinib mesylate, Glivec, Tuberculosis, Granuloma, PET-CT     

Radiographic quantification of alveolar bone level changes. Predictors of longitudinal bone loss

The purpose of the present study was to determine the relative importance of a set of predictors for the radiographic change in alveolar bone level over 2 years in a group of 180 subjects and to assess the fit of the applied multivariate model. The included predictors were age, sex, initial bone level, type of initial lesion, tooth type, proximal tooth surface, calculus, and the presence of metal crowns or proximal fillings. The multivariate method of choice was multiple classification analysis. The results indicated that in descending order tooth type, initial bone level, and age were the most important predictors. Sex, calculus, and crown and filling margins also showed significant direct effects (beta) on longitudinal bone loss (p less than 0.05). However, their relative importance was far less than that of tooth type, initial bone level, and age. Proximal side showed no significant direct effect. Using seven predictors, the applied multivariate model explained 20% of the variance in longitudinal bone loss.     

A new solution for the removal of the smear layer

Various organic acids, ultrasonic instruments, and lasers have been used to remove the smear layer from the surface of instrumented root canals. The purpose of this study was to investigate the effect of a mixture of a tetracycline isomer, an acid, and a detergent (MTAD) as a final rinse on the surface of instrumented root canals. Forty-eight extracted maxillary and mandibular single-rooted human teeth were prepared by using a combination of passive step-back and rotary 0.04 taper nickel-titanium files. Sterile distilled water or 5.25% sodium hypochlorite was used as intracanal irrigant. The canals were then treated with 5 ml of one of the following solutions as a final rinse: sterile distilled water, 5.25% sodium hypochlorite, 17% EDTA, or a new solution, MTAD. The presence or absence of smear layer and the amount of erosion on the surface of the root canal walls at the coronal, middle, and apical portion of each canal were examined under a scanning electron microscope. The results show that MTAD is an effective solution for the removal of the smear layer and does not significantly change the structure of the dentinal tubules when canals are irrigated with sodium hypochlorite and followed with a final rinse of MTAD.     

Carbetocin versus oxytocin for prevention of postpartum hemorrhage in obese nulliparous women undergoing emergency cesarean delivery

Objective: To assess and compare the effectiveness and safety of single IV polus dose of carbetocin, versus IV oxytocin infusion in the prevention of PPH in obese nulliparous women undergoing emergency Cesarean Delivery.

Methods: A double-blinded randomized-controlled trial was conducted on 180 pregnant women with BMI >30. Women were randomized to receive either oxytocin or carbetocin during C.S. The primary outcome measure was major primary PPH >1000?ml within 24?h of delivery as per the definition of PPH by the World Health Organization Secondary outcome measures were hemoglobin and hematocrit changes pre- and post-delivery, use of further ecobolics, uterine tone 2 and 12-h postpartum and adverse effects.

Results: A significant difference in the amount of estimated blood loss or the incidence of primary postpartum haemorrhage (>1000?ml) in both groups. Haemoglobin levels before and 24-h postpartum was similar. None from the carbetocin group versus 71.5% in oxytocin group needed additional utrotonics (p?<?0.01). The uterine contractility was better in the carbetocin group at 2, and 12-h postpartum (p?<?0.05).

Conclusions: A single 100-µg IV carbetocin is more effective than IV oxytocin infusion for maintaining adequate uterine tone and preventing postpartum bleeding in obese nulliparous women undergoing emergency cesarean delivery, both has similar safety profile and minor hemodynamic effect.     

Integrative mid-trimester anomaly (IMTA) chart: a novel sonographic approach for syndromatic challenges (pilot study)

Objective: To validate the use of the integrative mid-trimester anomaly (IMTA) chart, a novel chart that aims to increase sonographers’ ability to diagnose fetal syndromes and complex anomalies.

Methods: This study was conducted between September 2014 and January 2015. Pregnant women who attended our hospital for fetal medicine consultation during the second trimester were recruited. The diagnosis was assigned by a qualified consultant. The research coordinator randomized women between two groups (each consisted of two sonographers with comparable experience) and each was then examined twice (once with and once without the chart). Supposed diagnosis, patient and sonographer satisfactions were reported.

Results: Twenty five women were recruited. Their average age was 26.48?±?4.49 years and gestational age at examination was 24.39?±?6.39. There were 17 (68%) fetuses that had multiple anomalies. The duration of examination was comparable. However, patient and sonographer satisfactions were higher when the same women were examined with the chart (p?<?0.0001). The accuracy of diagnosis was also significantly higher (p?=?0.03).

Conclusion: The IMTA chart seems to be a useful tool for novice sonographers that could increase their diagnostic accuracy and improve their patient and their own satisfaction.     

Biochemical,histopathological, and transmission electron microscopic ultrastructural changes in mice after exposure to silver nanoparticles

Four‐week‐old mice, weighing about 25–35 g were divided into five groups (8 mice in each group): vehicle control, low‐ (0.5 g/kg), middle‐ (1 g/kg), high‐ (3 g/kg), and exceptionally high‐dose (5 g/kg). After first and second weeks of intraperitoneal exposure to AgNPs, biochemical, histopathological, and electron microscopic ultrastructural changes were investigated. No significant changes were observed in SGOT and ALP levels after first week of exposure, while the level of SGPT significantly increased (p < 0.05) in 2nd week treated mice, indicating that inflammatory of liver might be induced by high‐dose (3 and 5 g/kg) of AgNPs. No obvious changes were observed for UA and BUN in all groups of treated mice. However, significant (p < 0.05) decrease in CR level was noticed in all groups of treated mice only at high‐dose (3 and 5 g/kg). No remarkable changes in lipid profile were observed. Light microscopic histopathological investigation shows that first week treatment had not perceptible effect on the cytoarchitecture on liver, kidney, and spleen; while, second week treatment had only sporadic mild effects on these organs. However, no ultrastructural electron microscopic changes were observed in liver, kidney, and spleen of mice treated with 0.5, 1, and 3 g/kg of AgNPs when sacrificed on first and second week; while, exceptionally high‐dose (5 g/kg) of AgNPs resulted in slight nuclear chromatin condensation and irregularities in nuclear membrane. The results suggested that AgNPs could be well tolerated in mice when given intraperitoneally and no death has been found during the experiment in any groups of treated mice. Interestingly, significant (<0.05) decrease in glucose levels in all experiment group is suggestive of curious hypoglycemic role of AgNPs warranting further study to explore its possible therapeutic potential in hyperglycemic conditions as well as its mechanism of action at molecular level. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 945–956, 2016.     

Evaluation of cytotoxicity and genotoxicity of pesticide mixtures on lymphocytes

The cytotoxicity and genotoxicity of pesticide mixtures viz. endosulfan?+?chlorpyrifos, chlorpyrifos?+?profenofos, and endosulfan?+?profenofos were evaluated on cultured human peripheral blood lymphocytes using assays for cell viability, and genotoxicity using chromosomal aberrations test and comet assay. The LC₅₀ values for cytotoxicity were 3.50?μM, 4.18?μM, and 10.5?μM for profenofos, endosulfan, and chlorpyrifos respectively. When combined in equimolar concentrations, the LC₅₀ values for cytotoxicity were 1.4?μM, 1.8?μM, and 2.0?μM for endosulfan?+?chlorpyrifos, chlorpyrifos?+?profenofos, and endosulfan?+?profenofos, respectively. Higher concentrations of individual pesticides (0.5–4.0?μM) but very low concentrations of pesticide mixtures caused significant DNA damage. Additive index values indicated a synergistic effect of toxicity for endosulfan?+?chlorpyrifos combination (1.12 TTU). The binary mixture of chlorpyrifos?+?profenofos showed an additive toxicity (0.46 TTU) while an antagonistic effect was observed for endosulfan?+?profenofos combination. Synergism could be due to these complementary pesticides simultaneously acting in different ways, magnifying their efficacy, whereas an additive interaction would imply that the chemicals are acting by the same mechanism and at the same target. Analysis of toxicity of pesticide mixtures may serve as important biomarker for occupational and household exposure to pesticides, with different modes of action.     

Betulinic Acid: Recent Advances in Chemical Modifications,Effective Delivery,and Molecular Mechanisms of a Promising Anticancer Therapy

An important method of drug discovery is examination of diverse life forms, including medicinal plants and natural products or bioactive compounds isolated from these sources. In cancer research, lead structures of compounds from natural sources can be used to design novel chemotherapies with enhanced biological properties. Betulinic acid (3β‐hydroxy‐lup‐20(29)‐en‐28‐oic acid or BetA) is a naturally occurring pentacyclic triterpene with a wide variety of biological activities, including potent antitumor properties. Non‐malignant cells and normal tissues are not affected by BetA. Because BetA exerts its effects directly on the mitochondrion and triggers death of cancerous cells, it is an important alternative when certain chemotherapy drugs fail. Mitochondrion‐targeted agents such as BetA hold great promise to circumvent drug resistance in human cancers. BetA is being developed by a large network of clinical trial groups with the support of the U.S. National Cancer Institute. This article discusses recent advances in research into anticancer activity of BetA, relevant modes of delivery, and the agent's therapeutic efficacy, mechanism of action, and future perspective as a pipeline anticancer drug. BetA is a potentially important agent in cancer therapeutics.