In vivo phosphorus polarization transfer and decoupling from protons in three-dimensional localized nuclear magnetic resonance spectroscopy of human brain

Refocused insensitive nucleus enhancement by polarization transfer (RINEPT) from protons (¹H) to a J-coupled phosphorus (³¹P) has been incorporated into three-dimensional (3D) chemical-shift-imaging (CSI) sequence on a clinical imager. The technique is demonstrated on a phantom and in in vivo human brain. The polarization-transfer efficiency (～1.2) is lower than the theoretical maximum of γ¹H/γ³¹P≈ 2.4 resulting from ¹H-¹H homonuclear J couplings of similar magnitude competing with the ¹H →³¹P transfer. Nevertheless, compared with direct ³¹P Ernst-angle excitation, signal gains of up to × 1.8 were obtained mainly as a result of T¹ differences between ³¹P and the ¹H. Spectral interpretation is simplified by editing out all non-proton-coupled ³¹P signals. The duration, ～50 min, and power deposition, ～1 W · kg^?1, make the application suitable for human studies.     

Time in hemodialysis modulates the levels of genetic damage in hemodialysis patients

It is assumed that hemodialysis treatment can diminish the levels of genetic damage in circulating lymphocytes by cleaning the blood of uremic toxins that cause oxidative stress. However, the hemodialysis process by itself may also induce genomic damage by producing reactive oxygen species (ROS). We conducted a follow‐up study in a group of 70 hemodialysis patients followed for a mean time of 15 months. We investigated the effect of exposure time in hemodialysis on the levels of genetic damage in peripheral blood lymphocytes using the micronucleus assay. In addition, genetic damage after in vitro irradiation with 0.5 Gy was also analyzed to evaluate changes in radiosensitivity. Our results showed that, at the end of the study, there was a decrease in both the basal levels of genetic damage (9.9 ± 1.0 vs. 7.6 ± 0.7) and radiosensitivity values (38.5 ± 3.0 vs. 27.6 ± 2.4). We conclude that hemodialysis procedures may act as an ameliorating factor reducing the genetic damage present in chronic kidney disease patients. Environ. Mol. Mutagen. 55:363–368, 2014. © 2014 Wiley Periodicals, Inc.     

Genomic damage as a biomarker of chronic kidney disease status

Patients suffering from chronic kidney disease (CKD) exhibit a high incidence of cancer and cardiovascular diseases, as well as high levels of genomic damage. To confirm the association of CKD with genomic damage we have carried out the largest study to date addressing this issue, using a total of 602 subjects (187 controls, 206 pre‐dialysis CKD patients and 209 CKD patients in hemodialysis). DNA oxidative damage was measured in all individuals using the comet assay. Our results indicate that CKD patients have significantly higher levels of DNA damage than controls, but no significant differences were observed between pre‐hemodialysis (pre‐HD) and hemodialysis (HD) patients. When oxidative damage was measured, no differences were observed between patients and controls, although HD patients showed significantly higher levels of oxidative damage than pre‐HD patients. In addition, a positive relationship was demonstrated between genomic damage and all‐cause mortality. Our study confirms that genomic damage can be predictive of prognosis in CKD patients, with high levels of DNA damage indicating a poor prognosis in HD patients. Environ. Mol. Mutagen. 56:301–312, 2015. © 2014 Wiley Periodicals, Inc.     

Managing Uncertainty: Healthcare Professionals' Meanings Regarding the HPV Vaccine

Background

New preventive technologies such as vaccines offer insight into psychological, social, and cultural landscapes. Providers have a key role in parents' decisions for vaccinating their children. Yet, perspectives from providers regarding the human papillomavirus (HPV) vaccine, or vaccination in general, are rarely sought

Purpose

Our objective in this paper is to understand how the HPV vaccine is perceived by health care providers and the multiple contextual meanings it elicits.

Methods

We conducted interviews with 20 health care professionals in Bulgaria about their attitudes and practices related to HPV vaccination and their recommendations for policies. The verbatim-transcribed interviews were analyzed through narrative analysis, with a special focus on language.

Results

We illustrate providers' contradictory and contextualized constructions of the vaccine and the narrative strategies they use to manage any uncertainty it elicits. These include being advocates and missionaries for preventive health, confirming their trust in the medical profession and professional organizations, challenging patients' concerns with rational explanations, normalizing the risk of medical innovations, and avoiding the sexual nature of HPV transmission.

Conclusions

The introduction of a vaccine to prevent HPV infection, and by implication, possibly cervical and other cancers, created hope, and at the same time, intensified confusion and uncertainty. Providers have been frustrated for years with the rising mortality from cervical cancer in Bulgaria, and their perceived powerlessness in affecting this. HPV vaccination, on the other hand, seems relatively simple and “taming uncertainty” positions them as instrumental in limiting (or even eliminating) morbidity and mortality in future generations.     

The Role of 3-D Endorectal Ultrasound in Rectal Cancer: Our Experience

In the last 20 years, endorectal ultrasound (ERUS) has been one of the main diagnostic methods for locoregional staging of rectal cancer. ERUS is accurate modality for evaluating local invasion of rectal carcinoma into the rectal wall layers (T category). Adding the three-dimensional modality (3-D) increases the capabilities of this diagnostic tool in rectal cancer patients. We review the literature and report our experience in preoperative 3-D ERUS in rectal cancer staging. In the group of 71 patients, the staging of preoperative 3-D endorectal ultrasonography was compared with the postoperative morphologic examination. Three-dimensional ERUS preoperative staging was confirmed with morphologic evaluation in 66 out of 71 cases (92.9%). The detection sensitivities of rectal cancer with 3-D ERUS were as follows: T1, 92.8%; T2, 93.1%; T3, 91.6%; and T4, 100.0%; with specificity values of T1, 98.2%; T2, 95.4%; T3, 97.8%; and T4, 98.5%. Three-dimensional ERUS correctly categorized patients with T1, 97.1%; T2, 94.3%; T3, 95.7%; and T4, 98.5%. The percentage of total overstaged cases was 2.75% and that of understaged cases was 6.87%. The metastatic status of the lymph nodes was determined with a sensitivity of 79.1% (19 of 24), specificity of 91.4% (43 of 47), and diagnostic accuracy of 87.3% (62 of 71). In our experience, 3-D ERUS has the potential to become the diagnostic modality of choice for the preoperative staging of rectal cancer.Key words: Three-dimensional endorectal ultrasound, Rectal cancerEndorectal ultrasound (ERUS) has been used as a diagnostic tool for evaluation and staging of rectal cancer since the 1980s.¹ According to the literature, in studies with more than 50 patients included, an overall accuracy of approximately 81.8% was reported.² Most of the studies present data between 85% and 95%, but in the studies with more than 200 patients, the accuracy rates are relatively lower—63.3% and 69%, respectively.^3,4 A common disadvantage of ERUS and magnetic resonance imaging (MRI) is the overstaging of T2 tumors owing to an irregular outer rectal wall resulting from transmural tumor extension or inflammation around the tumor. Another challenge for the ERUS, and especially the rigid probes, are the locally advanced, stenotic tumors, where the probe may not be able to pass above the lesion.⁵ The nodal staging accuracy of ERUS ranges from 70% to 75%.^1,5,6 The metastatic lymph nodes are distinguished by hypoechoic appearance, round shape, peritumoral location, and size >5 mm.^7,8 Lymph nodes >5 mm have a 50% to 70% chance of being malignant, while those <4 mm have only a 20% chance.^9,10 A new modality of endorectal ultrasound represents a three-dimensional (3-D) ERUS that provides better visual images of the tumor volume and spatial relations to the adjacent organs and structures, even better than those of MRI, which leads to better diagnostic accuracy than MRI and standard ERUS.^11–15 The unique 3-D–ERUS longitudinal scan can precisely assess the tumor size and location.¹⁶ The most important feature of this upgraded modality is the ability to reduce interpreter errors and offer potential predictive value. Three-dimensional ERUS provides the possibility to distinguish blood vessels from lymph nodes and allow precise fine needle aspiration (FNA) biopsies.^13,17 The infiltration of circumferential margin has been proven to correlate with T category, lymph node metastasis histologic tumor differentiation, and lymphovascular invasion.^13,17 Three-dimensional ERUS gives the possibility of multiplane evaluation of the tumor, allowing visualization of more subtle changes in the tumor characteristics and therefore better T and N categorizing.¹⁸ A review of 86 patients who underwent standard 3-D ERUS, ERUS and 4-channel detector computed tomography (CT) demonstrated T-category accuracy of 78%, 69%, and 57%, respectively.¹⁹ After analysis of the examiner''s error, the accuracy of 3-D ERUS for T category has reached 91% for 3-D ERUS and 88% for standard ERUS, and the N category accuracy improved to 90% and 76%, respectively. Also, ERUS can be used for diagnosis of premalignant lesions such as adenomas and polyps.²⁰ The main goal is to properly identify any chance of tumor invasion in the primary lesion and involvement of the surrounding lymph nodes in case the absence of those alarming characteristics allows for endoscopic resection of the lesion. Using higher-resolution probes, ERUS can distinguish T0 from T1 lesions. According to a meta-analysis of 258 biopsy-negative tumors, ERUS identified tumor mass in 81% of the 24 lesions, which were found to be invasive tumors on morphologic examination.²⁰ Another series of 60 patients with pT0/pT1 lesions demonstrated sensitivity and specificity of ERUS 89% and 88%, respectively.²¹ As with MRI, 3-D ERUS could provide an evaluation of the mesorectal fascia.^14,22The reported data lead to the position that 3-D ERUS combines the high-resolution images of the rectal wall and cost-effectiveness of standard ERUS with the multiplanar and stereoscopic imaging capabilities of MRI. Three-dimensional ERUS may be the future premier imaging modality used in rectal cancer management.     

Synthesis and antibacterial activity of new arylamido derivatives of 6 beta-aminopenicillanic, 7 beta-aminocephalosporanic and 7 beta-aminodesacetoxycephalosporanic acids

New semisynthetic penicillins and cephalosporins have been synthesized by acylation of 6 beta-aminopenicillanic, 7 beta-aminocephalosporanic and 7 beta-aminodesacetoxycephalosporanic acids with ortho-substituted aromatic acids, using the method of mixed anhydrides. The chemical structures of the compounds obtained were confirmed by elemental analysis and by IR- and 1H-NMR spectra. Antibacterial activities of the compounds were determined by the macrodilution susceptibility test in brain-heart infusion broth. Test organisms producing beta-lactamases: Bacillus subtilis L2, Bacillus subtilis HB2, Bacillus cereus 30, Bacillus subtilis 6633 ATCC, Bacillus mycoides 924; Staphylococcus aureus 1/45 "Oxford" as Gram-positive bacteria, and Escherichia coli 111, Escherichia coli K12/F-?lac-/, Escherichia coli K12/F-?lambda-/, Escherichia coli K12/F-?lambda-?lac+/ as Gram-negative bacteria. In general, the derivatives of 6 beta-aminopenicillanic acid were more active than 7 beta-aminocephalosporanic and 7 beta-aminodesacetoxycephalosporanic acid derivatives. Among all the compounds synthesized 6 beta-[4'-(dimethylamino)-azobenzene-2-amido]penicillanic acid and 6 beta-(N-phenylanthranilamido)penicillanic acid showed the best activity and were with the broadest spectrum of action.     

Synthesis and antibacterial activity of 5-nitrofuryl and 3-methoxy-2-nitrophenyl derivatives of 6 beta-aminopenicillanic, 7 beta-aminocephalosporanic and 7 beta-aminodesacetoxy-cephalosporanic acids.

A number of 5-nitrofuryl and 3-methoxy-2-nitrophenyl derivatives of 6 beta-aminopenicillanic (6 beta-APA), 7 beta-aminocephalosporanic (7 beta-ACA) and 7 beta-aminodesacetoxycephalosporanic (7 beta-ADCA) acids were synthesized by the method of mixed anhydrides or via Schiff bases. The chemical structures of the new compounds were confirmed by IR-, 1H-NMR and mass spectral data, obtained by negative ion electrospray ionization. The in vitro testing results indicated that all penicillins and cephalosporins prepared exhibited antibacterial activity equal to or in many cases considerably higher than those of ampicillin (CAS 69-53-4) and cephalexin (CAS 23325-78-2) against the Gram-positive microorganisms, excluding B. subtilis L2, B. subtilis HB2 and S. aureus 1/45 "Oxford". Their activity towards the two strains of Proteus mirabilis was also good being greater than that of cephalexin contrary to the demonstrated lower activity towards all strains of E. coli tested. The most active compounds which simultaneously possessed the broadest spectrum of antibacterial activity proved to be compounds 1 and 8 both bearing as a substituent a 5-nitrofuran group.     

A case of undifferentiated (embryonal) sarcoma of the liver: fine needle aspiration cytology diagnosis by one cell type

We present the first case in Bulgaria of cytologically verified undifferentiated (embryonal) sarcoma of the liver. A 10-year-old girl was admitted to the hospital with abdominal pain, extreme hepatomegaly, one-month fever, anemia and highly elevated erythrocyte sedimentation rate (95 mm). A large formation was found in the right liver lobe on ultrasound examination, which was polycystic on CT scan. Neither bone marrow abnormalities nor elevation of serum alpha-fetoprotein was found. In the scanty specimen obtained by fine-needle aspiration biopsy under ultrasound control a characteristic prevalence of polygonal cells within mesenchyme tissue was found. The cells had eccentric hyperchromic nuclei which were pushed to the periphery by large clusters of PAS-positive, diastase-resistant granules. Vimentin and alpha 1-antitrypsyn were expressed immunohistochemically. The cells are pathognomonic of undifferentiated (embryonal) sarcoma of the liver. After preoperative chemotherapy with ifosfamide, vincristine and actinomycin D (CEVAIE, CWS--96) resection of the tumor including IV, V, VI and VII liver segments was performed. A 30 x 30-cm soft gray-whitish tumor with fine capsule was found. The cytological diagnosis was histologically verified. The patient had a mechanical subileus episode after the 6th course of chemotherapy. One year after the surgery she is in good condition. The histogenesis of this rare tumor is discussed regarding its unique cytology, immunohistochemical constellation and ultrastructure. A literature review is presented. The case indicates that the unique cell appearance in embryonal sarcoma of the liver provides a correct diagnosis even in a scanty specimen.