Use of the competing-hypotheses heuristic to reduce 'pseudodiagnosticity'

A quasiexperimental research design involving a nonequivalent control group was used to examine the efficacy of a brief educational intervention in teaching medical students to select optimal diagnostic data consistent with the competing-hypotheses heuristic and Bayes' theorem when solving clinical problems. There was no significant difference between intervention (n = 119) and control (n = 89) groups in performance at baseline, but the intervention group performed significantly better (p less than .001) than the control group after training. The results suggest that some problem-solving skills, such as learning to use the competing-hypotheses heuristic, can be enhanced or learned independent of the acquisition of content knowledge.     

Serum lipase assay. A test of choice in acute pancreatitis.

We evaluated the clinical accuracy of an automated turbidimetric assay for serum lipase determination in order to screen for acute pancreatic damage. Seventy patients with pancreatic and thirty with nonpancreatic digestive diseases were studied. Fifty-two healthy subjects were also studied as controls. Serum lipase concentrations were abnormally high in all patients with acute pancreatitis and in 3 (10%) in the group of 30 patients with nonpancreatic acute abdomen. In the 35 patients with chronic pancreatitis studied during clinical remission, serum lipase levels were abnormally high in 8 (23%), and abnormally low in 3 (9%). In the 9 patients with pancreatic cancer, 4 (44%) had abnormally elevated serum lipase values and 1 (11%) abnormally low. The results indicate that serum lipase determination is useful in the emergency diagnosis of acute pancreatic damage because of its high sensitivity and specificity. In patients with chronic pancreatitis and in patients with pancreatic carcinoma serum lipase determination is of limited value.     

Pseudo-angiomatous hyperplasia of mammary stroma: a case with gigantomastia

Pseudo-angiomatous hyperplasia of mammary stroma (PASH) is a histopathological entity which is a microscopic fortuitous finding in mammary biopsies performed for different reasons. It may be symptomatic and appears then as a palpable lump. The term pseudo-angiomatous emphasizes the characteristic aspect of the stroma simulating a vascular tumor. We report a case of PASH in a 71 year-old woman who presented a recurring breast mass with rapid swelling of the mammary gland (70 x 60 x 20 cm) treated by mastectomy. PASH must be distinguished from a well-differentiated angiosarcoma. It is ruled out by immunohistochemistry.     

ALK Expression Defines a Distinct Group of T/Null Lymphomas (“ALK Lymphomas”) with a Wide Morphological Spectrum

The t(2;5)(p23;q35) translocation associated with CD30-positive anaplastic large cell lymphoma results in the production of a NPM-ALK chimeric protein, consisting of the N-terminal portion of the NPM protein joined to the entire cytoplasmic domain of the neural receptor tyrosine kinase ALK. The ALK gene products were identified in paraffin sections by using a new anti-ALK (cytoplasmic portion) monoclonal antibody (ALKc) that tends to react more strongly than a previously described ALK1 antibody with the nuclei of ALK-expressing tumor cells after microwave heating in 1 mmol/L ethylenediaminetetraacetic acid buffer, pH 8.0. The ALKc monoclonal antibody reacted selectively with 60% of anaplastic large cell lymphoma cases (60 of 100), which occurred mainly in the first three decades of life and consistently displayed a T/null phenotype. This group of ALK-positive tumors showed a wide morphological spectrum including cases with features of anaplastic large cell lymphoma “common” type (75%), “lymphohistiocytic” (10%), “small cell” (8.3%), “giant cell” (3.3%), and “Hodgkin’s like” (3.3%). CD30-positive large anaplastic cells expressing the ALK protein both in the cytoplasm and nucleus represented the dominant tumor population in the common, Hodgkin’s-like and giant cell types, but they were present at a smaller percentage (often with a perivascular distribution) also in cases with lymphohistiocytic and small cell features. In this study, the ALKc antibody also allowed us to identify small neoplastic cells (usually CD30 negative) with nucleus-restricted ALK positivity that were, by definition, more evident in the small cell variant but were also found in cases with lymphohistiocytic, common, and “Hodgkin’s-like” features. These findings, which have not been previously emphasized, strongly suggest that the neoplastic lesion (the NPM-ALK gene) must be present both in the large anaplastic and small tumor cells, and that ALK-positive lymphomas lie on a spectrum, their position being defined by the ratio of small to large neoplastic cells. Notably, about 15% of all ALK-positive lymphomas (usually of the common or giant cell variant) showed a cytoplasm-restricted ALK positivity, which suggests that the ALK gene may have fused with a partner(s) other than NPM. From a diagnostic point of view, detection of the ALK protein was useful in distinguishing anaplastic large cell lymphoma cases of lymphohistiocytic and small cell variants from reactive conditions and other peripheral T-cell lymphoma subtypes, as well as for detecting a small number of tumor cells in lymphohemopoietic tissues. In conclusion, ALK positivity appears to define a clinicopathological entity with a T/null phenotype (“ALK lymphomas”), but one that shows a wider spectrum of morphological patterns than has been appreciated in the past.     

Takayasu’s arteritis occurring under TNF blockers in a patient with spondyloarthritis: is it an association or a paradoxical effect?

Coexistence of spondyloarthritis (SpA) and Takayasu’s arteritis is not a common finding, but such cases have been discussed, particularly in the context of choice of therapy. Inhibition of inflammation by tumor necrosis factor inhibitors (TNFi) is a key aspect of the treatment of SpA and also positive effects of such treatment in concomitant large vessel vasculitis have been reported. However, TNFi is also associated with the possibility of initiating vasculitis.The present article based on a case study and the available literature is an attempt to discuss coexistence of these two diseases and the impact of treatment with biological drugs from the anti-TNF group in the course of SpA with Takayasu’s arteritis.     

The use of the peripheral leukocyte count and chest X-rays in early assessment of the severity of acute pancreatitis in comparison with the Ranson score system

BACKGROUND: To evaluate the efficacy of the peripheral leukocyte count and chest X-rays as an index which could be used in the early assessment of the severity of acute pancreatitis in an Emergency Room. METHODS: We prospectively evaluated the peripheral leukocyte count and the findings of chest X-rays in 181 consecutive patients (102 males, 79 females, mean age 61 years, range 16-97) who were admitted to our Emergency Department with acute pancreatitis. One hundred twenty six patients had mild pancreatitis and 55 had severe pancreatitis. The peripheral leukocyte count and the chest X-rays were evaluated in all patients upon admission. The Ranson criteria were also assessed. RESULTS: Using a cut off value of 13,000/mm3, 45% of the patients with severe pancreatitis and 17% of those with mild acute pancreatitis had a peripheral leukocyte count greater than 13,000/mm3. Pleural or pulmonary alterations observed on chest X-ray were found in 66% of patients with severe pancreatitis and in 2% of those with mild acute pancreatitis. A peripheral leukocyte count greater than 13,000/mm3 and/or pleural or pulmonary alterations present on chest X-ray were found in 78% of the patients with severe pancreatitis and in 19% of those with mild pancreatitis. The Ranson criteria greater than or equal to three were found in 45% of the patients with severe acute pancreatitis and in 16% of those with the mild form of the disease. The positive predictive value was 92% for the presence of alterations on the chest X-rays, 64% for the alteration of at least one of the abnormal findings on the chest X-ray and a peripheral leukocyte count greater than 13,000/mm3, 56% for a peripheral leukocyte count greater than 13,000/mm3, and 54% for the presence of Ranson criteria greater than or equal to three. The negative predictive values were similar. CONCLUSIONS: The presence of pleural or pulmonary alterations on chest X-rays may be useful in the Emergency Room for the early identification of patients with severe acute pancreatitis.     

Effects of antisense oligonucleotide-mediated depletion of tumor necrosis factor (TNF) receptor 1-associated death domain protein on TNF-induced gene expression

Tumor necrosis factor (TNF) receptor 1-associated death domain protein (TRADD) is an adaptor protein known to be involved in the TNF signaling pathway as well as signaling of other members of the TNF receptor superfamily, including DR3, DR6, p75(NTR), and the Epstein-Barr virus latent membrane protein 1. Current knowledge of the function of the adaptor protein has been derived from studies examining its over-expression in either wild-type or mutated forms. In this study, we analyzed the consequences of antisense oligonucleotide (ASO)-mediated depletion of endogenous TRADD on TNF induction of inflammation-related gene products, such as intercellular adhesion molecule-1, and associated kinase signaling pathways in human umbilical vein endothelial cells. A broader perspective of TRADD's role in TNF signaling was indicated by microarray gene expression analysis, where 20 of 24 genes that showed a 5-fold or greater increase in TNF-induced mRNA expression levels displayed a reduction in TNF-induced expression as a consequence of ASO-mediated knockdown of TRADD. Reduced activation of the nuclear factor-kappaB and c-Jun NH(2)-terminal kinase pathways, as measured by IkappaB-alpha protein levels and the extent of c-Jun phosphorylation, was also observed. These results indicate usage of antisense inhibitors of TRADD expression for modulating diseases associated with TRADD-dependent signal transduction pathways.