John J. Baker

The biosynthesis of trimethylamine-N-oxide

Norris and Benoit (1) provided ‘good evidence that injected trimethylamine is converted in the rat to its N-oxide and excreted in the urine. Other mammals have been shown to have the ability to effect the same reaction (2, 3). In a preliminary communication (4), we have reported that hog liver microsomes will catalyze the oxidation of trimethylamine in vitro. The additional requirement for reduced triphosphopyridine nucleotide and oxygen makes this system analogous to a group of microsomal enzyme systems that also catalyze biological oxidations (5). Thus, a study of the oxidation of trimethylamine may yield information on microsomal oxidations in general. In this paper, evidence is presented that the product of trimethylamine oxidation is trimethylamine-N-oxide. Results of experiments to determine optimal conditions for this reaction and the effects of some potential inhibitors and activators are reported.

Whole slide imaging diagnostic concordance with light microscopy for breast needle biopsies

This study investigated the diagnostic accuracy of whole slide imaging (WSI) in breast needle biopsy diagnosis in comparison with standard light microscopy (LM). The study examined the effects of image capture magnification and computer monitor quality on diagnostic concordance of WSI and LM. Four pathologists rendered diagnoses using WSI to examine 85 breast biopsies (92 parts; 786 slides) consisting of benign and malignant cases. Each WSI case was evaluated using images captured at either ×20 or ×40 magnifications and viewed using a Digital Imaging and Communication in Medicine (DICOM) grade, color-calibrated monitor or a standard, desktop liquid-crystal display (LCD) monitor. For each combination, the WSI result was compared with the original, LM diagnosis. The overall concordance rate observed between WSI and LM was 97.1% (95% confidence intervals [CI]: 94.3%-98.5%). After a washout period, all cases were reviewed a second time by each pathologist after using LM, and the second LM diagnosis was compared with the WSI diagnosis rendered by the same pathologist. Intraobserver concordance between WSI and LM was 95.4% (95% CI: 92.2%-97.4%). The second LM diagnoses were also compared with the original LM diagnoses, and the observed interobserver LM concordance rate was 97.3% (95% CI: 93.1%-99.0%). The study data demonstrated that breast needle biopsy diagnoses rendered by WSI were equivalent to diagnoses rendered by LM. No diagnostic differences were detected between the underlying viewing system parameters of monitor quality and image capture resolution. The results of this study demonstrated that WSI can be effectively used in subspecialty diagnostic cases where a minimum amount of tissue is available.

Salivary duct carcinoma responding to trastuzumab-based therapy: case report and review of the literature.

Salivary duct carcinoma (SDC) is a rare malignancy with a poor prognosis. Human epidermal growth factor receptor‐2 (Her‐2/neu) is overexpressed in SDC and, hence, HER‐2/neu targeted therapy could be an option.

The Changing Face of Paranasal Sinus Fungus Balls

Objectives: We describe the clinical, radiographic, and histopathologic characteristics of fungus balls. Methods: We performed a retrospective review of 24 consecutive patients with the diagnosis of a paranasal sinus fungus ball (mycetoma) from 2001 to 2008. Results: We found that 18 of the 24 primarily involved sinuses had bony thickening, and 13 of the 24 had notable dilatation of the ostium. Eleven of the 24 patients were found to have some degree of immunocompromise (from organ transplantation, diabetes, etc). The patients immune status correlated with the type of fungus involved. (Mucor-like fungi were more common in immunocompetent patients, and aspergillus-like fungi were more common in immunocompromised patients.) Also, there was a predilection for immunocompetent patients to have dilatated ostia, whereas immunocompromised patients were more likely to have a nondilatated ostium (p = 0.019). Conclusions: Our series of paranasal sinus fungus balls defines a group of patients heretofore poorly described in the literature. Our data reveal an increased incidence in immunocompromised patients. We also found consistent radiographic patterns, correlations between immune status and the fungal pathogen, correlations between ostial enlargement and immune status, and the presence of cranial nerve pareses. These represent new findings that merit further study.

Visual memory effects on intraoperator study design: determining a minimum time gap between case reviews to reduce recall bias.

OBJECTIVES The objective of this research was to determine test intervals between intraoperator case reviews to minimize the impact of recall. METHODS Three pathologists were presented with a group of 120 slides and subsequently challenged with a study set of 120 slides after 2-week and 4-week intervals. The challenge set consisted of 60 slides seen during the initial review and 60 slides previously unseen within the study. Pathologists rendered a diagnosis for each slide and indicated whether they recalled seeing the slide previously (yes/no). RESULTS Two weeks after having been shown 60 cases from a challenge set of 120 cases, the pathologists correctly remembered 26, 22, and 24 cases or 40% overall. After 4 weeks, the pathologists correctly recalled 31% of cases previously seen. CONCLUSIONS Pathologists were capable of recalling from memory cases seen previously at 2 and 4 weeks. Recall rates may be sufficiently high to affect intraobserver study design.

Investigation of scanning parameters for thyroid fine needle aspiration cytology specimens: A pilot study

Background: Interest in developing more feasible and affordable applications of virtual microscopy in the field of cytology continues to grow. Aims: The aim of this study was to investigate the scanning parameters for the thyroid fine needle aspiration (FNA) cytology specimens. Subjects and Methods: A total of twelve glass slides from thyroid FNA cytology specimens were digitized at ×40 with 1 micron (μ) interval using seven focal plane (FP) levels (Group 1), five FP levels (Group 2), and three FP levels (Group 3) using iScan Coreo Au scanner (Ventana, AZ, USA) producing 36 virtual images (VI). With an average wash out period of 2 days, three participants diagnosed the preannotated cells of Groups 1, 2, and 3 using BioImagene′s Image Viewer (version 3.1) (Ventana, Inc., Tucson, AZ, USA), and the corresponding 12 glass slides (Group 4) using conventional light microscopy. Results: All three raters correctly identified and showed complete agreement on the glass and VI for: 86% of the cases at FP Level 3, 83% of the cases at both the FP Levels 5 and 7. The intra-observer concordance between the glass slides and VI for all three raters was highest (97%) for Level 3 and glass, same (94%) for Level 5 and glass; and Level 7 and glass. The inter-rater reliability was found to be highest for the glass slides, and three FP levels (77%), followed by five FP levels (69.5%), and seven FP levels (69.1%). Conclusions: This pilot study found that among the three different FP levels, the VI digitized using three FP levels had slightly higher concordance, intra-observer concordance, and inter-rater reliability. Scanning additional levels above three FP levels did not improve concordance. We believe that there is no added benefit of acquiring five FP levels or more especially when considering the file size, and storage costs. Hence, this study reports that FP level three and 1 μ could be the potential scanning parameters for the thyroid FNA cytology specimens.