Autopsy Standardized Mortality Review: A Pilot Study Offering a Methodology for Improved Patient Outcomes.

A standardized mortality review of hospital autopsies identified discrepancies between clinical diagnoses and autopsy findings, unexpected deaths, adequacy of diagnostic workup, presence of adverse event, and type of a quality issue if present. The standardized review elements were chosen based on a review of quality metrics commonly used by hospitals. The review was completed by the pathologist based on their initial autopsy findings. The final autopsy report was later reviewed to confirm the initial review findings. Major discrepancies in diagnosis were categorized as class I or II based on the modified Goldman criteria. Ninety-six hospital autopsy cases from January 2015 to February 2018 were included in the study. The overall major discrepancy rate was 27%. Class I discrepancies, where a diagnosis found at autopsy might have improved survival had it been made premortem, were identified in 16% of cases. Categories associated with increased discrepancy rates included unexpected deaths, inadequate workup, abnormal labs or imaging not addressed, and certain quality issues. Deaths not expected at admission but expected at the time of death, those with adverse events, those within 48 hours of a procedure, those within 48 hours of admission, those with physician-specific quality issues, and those with system or process issues were not significantly related to diagnostic accuracy.

Synthesis and biological activity of L-tyrosine-based PPARgamma agonists with reduced molecular weight.

A series of PPARgamma agonists were synthesized from L-tyrosine that incorporated low molecular weight N-substituents. The most potent analogue, pyrrole (4e), demonstrated a K(i) of 6.9nM and an EC(50) of 4.7nM in PPARgamma binding and functional assays, respectively. Pyrrole (4e), which is readily synthesized from L-tyrosine methyl ester in four steps, also demonstrated in vivo activity in a rodent model of Type 2 diabetes.

Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists.

Elevated levels of the hormone resistin, which is secreted by fat cells, are proposed to cause insulin resistance and to serve as a link between obesity and type 2 diabetes. In this report we show that resistin expression is significantly decreased in the white adipose tissue of several different models of obesity including the ob/ob, db/db, tub/tub, and KKA(y) mice compared with their lean counterparts. Furthermore, in response to several different classes of antidiabetic peroxisome proliferator-activated receptor gamma agonists, adipose tissue resistin expression is increased in both ob/ob mice and Zucker diabetic fatty rats. These data demonstrate that experimental obesity in rodents is associated with severely defective resistin expression, and decreases in resistin expression are not required for the antidiabetic actions of peroxisome proliferator-activated receptor gamma agonists.

A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport.

The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of the fibrate drugs and the antidiabetic effects of the glitazone drugs in humans are due to activation of the alpha (NR1C1) and gamma (NR1C3) subtypes, respectively. By contrast, the therapeutic potential of the delta (NR1C2) subtype is unknown, due in part to the lack of selective ligands. We have used combinatorial chemistry and structure-based drug design to develop a potent and subtype-selective PPARdelta agonist, GW501516. In macrophages, fibroblasts, and intestinal cells, GW501516 increases expression of the reverse cholesterol transporter ATP-binding cassette A1 and induces apolipoprotein A1-specific cholesterol efflux. When dosed to insulin-resistant middle-aged obese rhesus monkeys, GW501516 causes a dramatic dose-dependent rise in serum high density lipoprotein cholesterol while lowering the levels of small-dense low density lipoprotein, fasting triglycerides, and fasting insulin. Our results suggest that PPARdelta agonists may be effective drugs to increase reverse cholesterol transport and decrease cardiovascular disease associated with the metabolic syndrome X.

Image processing in forensic pathology.

Image processing applications in forensic pathology are becoming increasingly important. This article introduces basic concepts in image processing as applied to problems in forensic pathology in a non-mathematical context. Discussions of contrast enhancement, digital encoding, compression, deblurring, and other topics are presented.

Three-dimensional visualization and image processing in the evaluation of patterned injuries. The AFIP/UNC experience in the Rodney King case.

We used image processing to elucidate patterned injuries in a case of assault with a police baton. Three-dimensional visualization techniques were then used to correlate the location of patterned injuries with subjacent fracture and soft tissue damage. The visualization methods are discussed.

Enumeration of interphase chromosomes. Comparison of visual in situ hybridization and confocal fluorescence in situ hybridization.

OBJECTIVE: To compare two visual enumeration methods to determine whether the confocal approach yielded better counts of chromosome-specific hybridization sites. STUDY DESIGN: Brightfield microscopy was used to count in situ hybridization (ISH) sites in 4-microns tissue sections. Confocal microscopy was used to collect three-dimensional (3D) data sets from fluorescence in situ hybridization (FISH) preparations made with sections of various thicknesses. Analysis of the confocal images relied on custom-built interactive visualization software. RESULTS: The confocal method yielded higher average counts of hybridization sites per nucleus due to fewer truncated nuclei in thicker sections and to visual exclusion of the truncated nuclei that remained. Optimal section thickness was 8-12 microns. Limited penetration by FISH reagents restricted the use of thicker sections. CONCLUSION: Analysis of intact nuclei visualized in three dimensions was more sensitive in demonstrating high centromere number than was brightfield ISH analysis of 4-microns sections. Improvements in semiautomated interactive software may make the confocal approach practical for accurate evaluation of chromosome number in precise histologic contexts.

Three-dimensional reconstruction of a bullet path: validation by computed radiography.

Three-dimensional visualization is an important tool in the evaluation and demonstration of injury. Creating convincing graphics, however, requires strict distinction between illustrative and reconstructive visualizations and a method of validation. We present a case in which we used a radiation-planning tool to provide a 3-dimensional illustrative visualization of a contact gunshot wound to the head, and validated the result by comparing computed radiographs with radiographs taken at autopsy. We discuss the use of visualization tools for data exploration in forensic pathology.

Cell locomotion as shape change.

Although a great deal of understanding of blood cell locomotion can be derived from the evaluation of cell paths, cell movement may also be examined by evaluating how the cell changes shape as it moves. In order to understand how a cell changes shape, it is first necessary to be able to quantitatively describe cell shape and cell shape change. A review of current work in computer vision and shape description as applied to blood cells is presented.

Primary Ewing's sarcoma involving the bones of the head and neck.

Ewing's sarcoma is a rare tumor of the bone. In the Intergroup Ewing's Sarcoma Study (IESS) approximately 4% of the primary bone tumors arose in the bones of the head and neck. The mean age of patients was 10.9 years; boys slightly dominated the group. Signs and symptoms were local in distribution, with a mass or swelling most frequent. As in other sites, we categorized the dominant histologic pattern as diffuse or filigree, the latter carrying a more unfavorable prognosis. The radiographic appearance may be atypical as compared to Ewing's sarcoma at other sites. Prognosis of head and neck Ewing's is significantly better than Ewing's sarcoma overall. The gnathic bones were commonly affected, yet there was no associated mortality. No patient with primary disease in the bones of the head and neck who survived for 5 years on any of the IESS protocols has subsequently died.

Hierarchical shape description via the multiresolution symmetric axis transform.

A method is proposed that produces a shape description in the form of a hierarchy by scale of simple symmetric axis sequences. An axis segment that is a child of another has smaller scale and is seen as a branch of its parent. The scale value and parent-child relationship are induced by following the symmetric axis under successive reduction of resolution. The result, in two or three dimensions, is a figure¿rather than boundary¿oriented shape description that has natural segments and is insensitive to noise in the object description. The general approach of hierarchy production by following a feature through successive resolution reduction will be presented, as will methods of resolution reduction and computer implementation. Also, the relation of this figure-based shape description to those based on boundary curvature will be briefly discussed.

Juxtadrenal schwannoma: verification of the diagnosis by immunohistochemical and ultrastructural studies.

Solitary schwannomas arising in the juxtadrenal region are exceedingly rare. A middle-aged woman with a confusing clinical course was found to have a solid periadrenal mass, which was surgically excised. The gross and light microscopic appearance of the tumor was suggestive but not diagnostic of this entity. However, electron microscopic evaluation of the neoplasm revealed prominent basal lamina and interdigitating cellular processes characteristic of a schwannoma. The diagnosis of schwannoma was further supported by the demonstration of S-100 protein, type IV (basement membrane) collagen, and laminin immunoreactivity by immunohistochemical techniques. The use of these special studies to arrive at the diagnosis in this case and in the larger context in the diagnosis of rare adrenal and periadrenal tumors of uncertain origin is fully discussed.

Correlations between female sex roles and attitudes toward male sexual dysfunction in thirty women.

This paper reports correlations between female sex role and attitudes toward male sexual dysfunction in a sample of 30 women. The findings mirror those of a related much larger study. Mechanisms that might explain these findings are explored.