Methylation profiling of benign and malignant breast lesions and its application to cytopathology.

Methylation of tumor suppressor genes has been implicated in breast cancer development. However, methylation profiles of different breast lesions, subtypes of carcinoma in particular, have not been examined in detail. In this study, we use methylation-specific PCR (MSP) to generate gene methylation profiles of different breast lesions and to test the clinical utility of such profiles. We examined the methylation status of three genes, RARbeta2, RASSF1A, and cyclin D2, on 102 samples of breast tissue, from benign (n = 36), to in situ carcinoma (n = 21), to invasive carcinoma (n = 45). We found that almost all cases of invasive carcinoma (96%) contained at least one methylated gene from our panel, whereas gene methylation was less common among benign lesions (42%) and in situ carcinoma (76%). Of the three genes, cyclin D2 methylation was most specific for malignancy because only 1 of 35 benign cases was methylated at this gene (1 case was not informative). The major histologic subtypes of invasive carcinoma show similar methylation profiles in the genes examined. We next performed MSP analysis on archival breast fine-needle aspiration (FNA) biopsy samples and corresponding surgical biopsy specimens and found a high concordance between the two types of specimens. We then analyzed 17 breast FNA biopsy samples with an indeterminate diagnosis. In this setting, MSP had a high specificity (100%) and modest sensitivity (67%) for identifying malignancy.     

Acceptance and effects of nasal lavage in volunteer woodworkers

Wood dust is an irritant and is carcinogenic to the nasal mucosa. It inhibits its own clearance from the nose. It therefore makes sense to lavage retained wood dust from the nose following exposure. To our knowledge this is the second study conducted to determine whether the procedure of nasal lavage reduces nasal symptoms in woodworkers. Forty-six woodworkers from 150 approached volunteered to trial nasal lavage using gravity fed, home-made unbuffered isotonic saline for 2 months in a crossover trial and then be followed-up a year later. The group reported significantly decreased nasal symptoms and over half continued to use nasal lavage voluntarily after 1 year. Results support the findings of the previous study that nasal lavage improves nasal symptoms and supplements those findings with data indicating patterns of voluntary usage following the study's conclusion. It is concluded that nasal lavage is an acceptable, effective and inexpensive option with minimal side effects for woodworkers who experience nasal symptoms and who wish to try the procedure.     

A patient-specific quality assurance study on absolute dose verification using ionization chambers of different volumes in RapidArc treatments

The recalculation of 1 fraction from a patient treatment plan on a phantom and subsequent measurements have become the norms for measurement-based verification, which combines the quality assurance recommendations that deal with the treatment planning system and the beam delivery system. This type of evaluation has prompted attention to measurement equipment and techniques. Ionization chambers are considered the gold standard because of their precision, availability, and relative ease of use. This study evaluates and compares 5 different ionization chambers: phantom combinations for verification in routine patient-specific quality assurance of RapidArc treatments. Fifteen different RapidArc plans conforming to the clinical standards were selected for the study. Verification plans were then created for each treatment plan with different chamber-phantom combinations scanned by computed tomography. This includes Medtec intensity modulated radiation therapy (IMRT) phantom with micro-ionization chamber (0.007 cm³) and pinpoint chamber (0.015 cm³), PTW-Octavius phantom with semiflex chamber (0.125 cm³) and 2D array (0.125 cm³), and indigenously made Circular wax phantom with 0.6 cm³ chamber. The measured isocenter absolute dose was compared with the treatment planning system (TPS) plan. The micro-ionization chamber shows more deviations when compared with semiflex and 0.6 cm³ with a maximum variation of ?4.76%, ?1.49%, and 2.23% for micro-ionization, semiflex, and farmer chambers, respectively. The positive variations indicate that the chamber with larger volume overestimates. Farmer chamber shows higher deviation when compared with 0.125 cm³. In general the deviation was found to be <1% with the semiflex and farmer chambers. A maximum variation of 2% was observed for the 0.007 cm³ ionization chamber, except in a few cases. Pinpoint chamber underestimates the calculated isocenter dose by a maximum of 4.8%. Absolute dose measurements using the semiflex ionization chamber with intermediate volume (0.125 cm³) shows good agreement with the TPS calculated among the detectors used in this study. Positioning is very important when using smaller volume chambers because they are more sensitive to geometrical errors within the treatment fields. It is also suggested to average the dose over the sensitive volume for larger-volume chambers. The ionization chamber-phantom combinations used in this study can be used interchangeably for routine RapidArc patient-specific quality assurance with a satisfactory accuracy for clinical practice.     

Use of bone marrow derived stem cells in a fracture non-union

This is an attempt of using in vitro cultured mesenchymal stem cells (MSCs) from bone marrow in joining of a fracture non-union. Bone marrow cells were obtained and differentially centrifuged for MSCs that were grown in vitro in mesenchymal stem cell basal medium aseptically, for 10 d. The cell mass was injected around the fracture non-union. Healthy conditions of development of tissue regeneration at the trauma site and due bone joining were recorded. It is concluded that in vitro cultured MSCs had a blithesome effect on the fracture non-union.     

Age-dependent impairment of IgG responses to glycosylphosphatidylinositol with equal exposure to Plasmodium falciparum among Javanese migrants to Papua,Indonesia

Immune responses directed at glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum may offer protection against symptomatic malaria. To independently explore the effect of age on generation of the anti-GPI IgG response, we measured serum anti-GPI IgGs in a longitudinal cohort of migrant Javanese children (6-12 years old) and adults (> or = 20 years old) with equivalent numbers of exposures to P. falciparum in Papua, Indonesia. While the peak response in adults was achieved after a single infection, comparable responses in children required > or = 3-4 infections. Significantly fewer children (16%) than adults (41%) showed a high (optical density > 0.44) anti-GPI IgG response (odds ratio [OR] = 3.8, 95% confidence interval [CI] = 2.3-6.3, P < 0.0001), and adults were more likely to show a persistently high response (OR = 5.5, 95% CI = 1.0-56.8, P = 0.03). However, the minority of children showing a strong response were significantly less likely to experience symptoms with subsequent parasitemia compared with those with a weak response (OR = 4.0, 95% CI = 1.1-13.8, P = 0.02). This effect was not seen among high- and low-responding adults (OR = 1.2, 95% CI = 0.5-2.8, P = 0.60). Host age, independent of cumulative exposure, apparently represents a key determinant of the quantitative and qualitative nature of the IgG response to P. falciparum GPI.