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Abstract Background The rising prevalence of obesity and metabolic syndrome (MetS) has received increased attention since both place individuals at risk for Type II diabetes and cardiovascular disease. Insulin resistance (IR) has been implicated in the pathogenesis of obesity and MetS in both children and adults and is a known independent cardiovascular risk factor. However measures of IR are not routinely performed in children while MetS or severe obesity when present, are considered as clinical markers for IR. Objective The study was undertaken to assess the utility of ATPIII defined metabolic syndrome (MetS) and severe obesity as predictors of insulin resistance (IR) in a group of 576 overweight children and adolescents attending a pediatric obesity clinic in Brooklyn. Methods Inclusion criteria were children ages 3–19, and body mass index > 95th percentile for age. MetS was defined using ATP III criteria, modified for age. IR was defined as upper tertile of homeostasis model assessment (HOMA) within 3 age groups (3–8, n = 122; 9–11, n = 164; 12–19, n = 290). Sensitivity, specificity, positive predictive values and odds ratios (OR) with 95% confidence intervals (CI) were calculated within age groups for predicting IR using MetS and severe obesity respectively. Results MetS was present in 45%, 48% and 42% of the respective age groups and significantly predicted IR only in the oldest group (OR = 2.0, 95% CI 1.2, 3.4; p = .006). Sensitivities were Conclusion The expression of IR in overweight children and adolescents is heterogeneous and MetS or severe obesity may not be sufficiently sensitive and specific indicators of insulin resistance. In addition to screening for MetS in overweight children markers for IR should be routinely performed. Further research is needed to establish threshold values of insulin measures in overweight children who may be at greater associated risk of adverse outcomes whether or not MetS is present.

Flow-cytometry (FC) is a powerful tool that can assist in lymphoma diagnosis in lymph node (LN) specimens. Although lymphoma diagnosis and classification are mainly based on tumor cell characteristics, surrounding cells are less employed in this process. We retrospectively investigated alterations in the ploidy status, proliferative cell fraction (PF) and the percentages of surrounding immune cells in 62 consecutive LN specimens with B-Cell Non-Hodgkin Lymphoma (B-NHL) that were submitted for FC evaluation between 2019-2022. Compared with indolent B-NHLs, aggressive B-NHLs show increased DNA aneuploidy and PF, increased monocytes, immature-granulocytes, mature granulocytes, CD8 + T-cells, Double-Negative-T-cells and Double-Positive-T-cells, and decreased total CD45 + cells, total lymphocytes, CD4 + T-cells and CD4/CD8 ratio. Receiver operating characteristic analysis determined PF > 6.8% and immature-granulocytes > 0.9% as optimal cutoffs with highest specificity and sensitivity in differentiating aggressive and indolent B-NHLs. These findings further strength the diagnostic value of DNA content analysis by FC and suggest the utilization of tumor surrounding immune cells in NHL diagnosis and classification., (© 2024. The Author(s).)

Gestational trophoblastic neoplasms are a group of trophoblastic tumors that include choriocarcinoma (CC), epithelioid trophoblastic tumors (ETTs), and placental site trophoblastic tumors (PSTTs). Mixed gestational trophoblastic neoplasms include combinations of CCs with ETTs and/or PSTTs; combinations of ETTs and PSTTs have also been described. This report describes the case of a 49-yr-old female with mixed ETT and PSTT discovered due to menstrual delay and a positive beta-human chorionic gonadotropin in serum 11 yr after normal pregnancy; it is an asymptomatic recurrence of the neoplasm after 2 yr. Moreover, only the ETT recurred without evidence of PSTT by biopsy and without any increase in human chorionic gonadotropin levels, even though human chorionic gonadotropin was positive in the first onset of the disease. We also reviewed published English literature, which revealed that there are only 36 cases of mixed trophoblastic tumors to date, of which pure mixed ETT and PSTT were reported only in four cases including our case. The most common combination is CC admixed with an ETT (52%), followed by CC with PSTT in 30.5%. CC admixed with an ETT and/or PSTT account for 83% of the cases, of which pure mixed ETT and PSTT were reported only in 4 cases (11%). The rarity of this condition entails reporting of all cases to facilitate future research and clinical management., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)

Hemorrhagic malignant pleural effusion (HMPE) is diagnosed in 47-50% of all malignant pleural effusions (MPE). The aim of this study is to evaluate clinical, radiological, and morphological manifestations of HMPE and results of talc pleurodesis treatment. This is a retrospective review of the medical charts of 135 MPE patients which consists of HMPE group (42 patients) and simple MPE group (63 patients) (median age 67.9 years; 43 males, 62 females). In HMPE vs. simple MPE patients, pronounced dyspnea (100% vs. 88.9%, P  = 0.024), chest pain (59.5% vs. 60.3%, P  = 1), general deterioration (78.6% vs. 74.6%, P  = 0.411) combined with large pleural effusion (81% vs. 50.8%, P  = 0.001), and thickening of parietal pleura (73.8% vs. 68.3%, P  = 0.349), all were more specific for HMPE. Cytological examination of HMPE showed more malignant pleural fluid cells (81% vs. 63.5%, P  = 0.043). Histological examination revealed poorly differentiated types of tumors in 69.05% of HMPE (bronchogenic 33.33%, intestinal 16.67%, breast 14.3%) vs. 7.94% of simple MPE. In 19 HMPE vs. 0 simple MPE patients, thoracoscopy showed bleeding nodules (94.7%) on thickened parietal pleura (84.2%). Pleurodesis with talc by slurry (59%) and poudrage (41%) was less effective in HMPE than in simple MPE patients after 1 month (failed response; 33.3% vs. 21.6, P  = 0.019), 3 months (42.9% vs. 25.7%, P  = 0.017), and 6 months (42.9% vs. 21.7%, P  = 0.035). Survival in HMPE was significantly lower (3.06 months vs. 5.37 months, P  = 0.0005). HMPE has more severe clinical, laboratory, radiological, and endoscopic manifestations due to a more poorly differentiated malignant process. Talc pleurodesis was less effective in HMPE, and survival was poor., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Indian Association of Surgical Oncology 2020.)

Background: Differential diagnosis between diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) becomes a challenge when adequate biopsy is unavailable. The present study aimed to investigate the applicability of DNA cell cycle analysis by flow cytometry (FC) for differentiating between CD10 + DLBCL and FL., Methods: Data were collected from 57 specimens where CD5 - /CD10 + /light chain restricted B cells were detected. DNA staining was performed using the Coulter DNA Prep Kit. Cell cycle fractions were evaluated by automatic analysis using the ModFit LT software., Results: Histopathological analysis confirmed the diagnosis of CD10 + FL in 30 specimens (52.6%), CD10 + DLBCL in 24 specimens (42.1%), and CD10 + Burkitt lymphoma in 3 specimens (5.3%). A significantly higher rate of DNA aneuploidy was detected among CD10 + DLBCL than FL specimens (50 vs. 13.3% respectively, p = .003). Likewise, DNA index was significantly higher in CD10 + DLBCL relative to FL (1.26 ± 0.35 vs. 1.04 ± 0.16 respectively, p = .004). Notably, the proportion of cells in the S-phase and proliferative fraction was significantly higher in CD10 + DLBCL than in CD10 + FL (S-phase: 15.97 ± 13.94 vs. 4.43 ± 4.41 mean ± SD, respectively, p < .0001; proliferative fraction: 18.87 ± 15.17 vs. 5.78 ± 7.04 mean ± SD, respectively, p = .0001). Using a receiver operating characteristic analysis, optimal cutoffs for S-phase ≥7% and proliferative fraction ≥9% were determined. These values could be used to differentiate between CD10 + DLBCL and CD10 + FL., Conclusion: Including DNA cell cycle analysis in the FC lymphoma assessment panel may be of diagnostic value in differentiating between CD10+ DLBCL and FL when adequate biopsy is unavailable., (© 2019 International Clinical Cytometry Society.)

An analog inner hair cell and auditory nerve circuit using a dual AGC model has been implemented using 0.35 micron mixed-signal technology. A fully-differential current-mode architecture is used and the ability to correct channel mismatch is evaluated with matched layouts as well as with digital current tuning. The Meddis test paradigm is used to examine the analog implementation's auditory processing capabilities and investigate the circuit's ability to correct DC mismatch. The correction techniques used demonstrate the analog inner hair cell and auditory nerve circuit's potential use in low-power, multiple-sensor analog biomimetic systems with highly reproducible signal processing blocks on a single massively parallel integrated circuit.

Systemic amyloidosis frequently involves the small intestine. However, its association with diverticular disease has been seldom reported to date. To draw attention to this rare but potentially harmful association, we herein present an additional case of small bowel diverticular disease associated with amyloidosis.

Purpose: Colorectal cancer studies typically include both colon and rectum tumors as a common entity, though this assumption is controversial and only minor differences have been reported at the molecular and epidemiologic level. We conducted a molecular study based on gene expression data of tumors from colon and rectum to assess the degree of similarity between these cancer sites at transcriptomic level., Experimental Design: A pooled analysis of 460 colon tumors and 100 rectum tumors from four data sets belonging to three independent studies was conducted. Microsatellite instable tumors were excluded as these are known to have a different expression profile and have a preferential proximal colon location. Expression differences were assessed with linear models, and significant genes were identified using adjustment for multiple comparisons., Results: Minor differences at a gene expression level were found between tumors arising in the proximal colon, distal colon, or rectum. Only several HOX genes were found to be associated with tumor location. More differences were found between proximal and distal colon than between distal colon and rectum., Conclusions: Microsatellite stable colorectal cancers do not show major transcriptomic differences for tumors arising in the colon or rectum. The small but consistent differences observed are largely driven by the HOX genes. These results may have important implications in the design and interpretation of studies in colorectal cancer., (©2011 AACR.)

Background: Spontaneous splenic rupture considered a relatively rare but life threatening. The three commonest causes of spontaneous splenic rupture are malignant hematological diseases, viral infections and local inflammatory and neoplastic disorders. We describe a unique and unusual case of inflammatory myofibroblastic tumor of the tail of pancreas presented with massively enlarged spleen and spontaneous splenic rupture., Case Presentation: A 19 years old male patient with no significant past medical history presented to emergency room with abdominal pain and fatigue. Massively enlarged spleen was detected. Hypotension and rapid reduction of hemoglobin level necessitated urgent laparatomy. About 1.75 liters of blood were found in abdominal cavity. A large tumor arising from the tail of pancreas and local rupture of an enlarged spleen adjacent to the tumor were detected. Distal pancreatectomy and splenectomy were performed. To our knowledge, we report the first case of massively enlarged spleen that was complicated with spontaneous splenic rupture as a result of splenic congestion due to mechanical obstruction caused by an inflammatory myofibroblastic tumor of the tail of pancreas. A review of the literature is also presented., Conclusion: Inflammatory myofibroblastic tumor of the tail of pancreas should be included in the differential diagnosis of the etiological causes of massively enlarged spleen and spontaneous splenic rupture.

Mammary-digital-nail syndrome is a novel phenotypic association consisting of anonychia onychodystrophy with hypoplasia or absence of distal phalanges in males and females, accompanied by juvenile hypertrophy of the breast in affected females. This newly described genetic trait presents an autosomal dominant inheritance pattern, with either reduced penetrance or germ-line mosaicism. Analysis of the pedigree, linkage studies followed by a genome-wide screen and by haplotype analysis defined the locus for the phenotype within a 12 cM (4.3 Mb) interval on chromosome 22q12.3-13.1. This chromosomal region has not been implicated before in genetic disorders of the mammary tissue or limbs. These data suggest a possibly novel signaling pathway affecting the organogenesis of limbs and mammary glands in humans.

Background: Multiple and large cysts, located in the cervical stroma, can cause significant enlargement of the cervix., Case: A woman with two large intracervical cysts, one complex, underwent evaluation with ultrasound and magnetic resonance imaging (MRI). Hysterectomy revealed Nabothian cysts., Conclusion: In rare cases in which the intracervical cysts assume very large dimensions, ultrasound and MRI can aid diagnosis, but may not always prevent the need for excision or hysterectomy.

Background: The trefoils factor family is a relatively new family of peptides. Their abundant expression in the epithelial cells of the gastrointestinal tract in the normal physiological state and in various ulcerative conditions suggests an important role in mucosal defense and repair. Infection with Helicobacter pylori interferes with normal mucosal activity., Objectives: To investigate whether H. pylori infection alters the expression of trefoils TFF1 and TFF2 in the gastric mucosa of patients with H. pylori-associated chronic active gastritis, positive or negative for the CagA strain., Methods: During investigation for dyspepsia, gastric biopsies and blood samples were obtained from patients who underwent upper gastrointestinal endoscopy. Rapid urease testing, histology for determination of H. pylori-associated CAG and Western analysis for TFF1 and TFF2 expression with antisera were performed. CagA state was determined using a commercial kit., Results: TFF2 expression was significantly reduced in both groups of patients with H. pylori-associated CAG compared to healthy patients without H. pylori infection, particularly in CagA-positive patients. TFF1 expression showed a tendency of reduction (not significant) in this group only., Conclusions: These results suggest that H. pylori-associated CAG has a deleterious effect on the expression of TFF2 in the gastric antrum. This reduced expression may contribute to the damage induced to the gastric mucosa by H. pylori.

Identification of microsatellite unstable (MSI-H) colorectal cancers (CRCs) is important not only for the identification of hereditary nonpolyposis colorectal cancer syndrome but also because MSI-H CRCs have a better prognosis and may respond differently to 5-fluorouracil-based chemotherapy. We present 2 nearly equivalent logistic regression models for clinical use that predict microsatellite instability based on the review of 1649 CRCs from patients of all ages collected in a population-based case control study in northern Israel. One hundred ninety-eight of these 1649 tumors demonstrated a high degree of microsatellite instability (12%). Multivariate analysis found that >2 tumor-infiltrating lymphocyte (TIL) cells per high-powered field, the lack of dirty necrosis, the presence of a Crohn-like reaction, right-sided location, any mucinous differentiation (mucinous or focally mucinous) and well or poor differentiation, and age less than 50 were all independent predictors of MSI-H. We developed 2 logistic regression models that differ only by the statistical approach used to analyze the number of TIL cells per high-powered field, where the slightly more accurate (and complex) model uses the log of the total number of TIL cells. The simpler clinical model uses a cut-off of 2>TIL cells per high-powered field. The accuracy of both models is high, with an 85.4% versus 85.0% probability of correctly classifying tumors as MSI-H. By employing the simpler model, pathologists can predict the likelihood of microsatellite instability by compiling the MSI probability score (Table 4 and Fig. 1) from simple histologic and clinical data available during sign-out. Our model shows that approximately 43% of CRCs have a MSI probability score of 1 or less and hence have little likelihood (<3%) of being MSI-H. Although this model is not perfect in predicting microsatellite instability, its use could improve the efficiency of expensive diagnostic testing.

Patients on chronic hemodialysis (HD) are at high risk for developing atherosclerosis and cardiovascular complications. Heparanase, an endoglycosidase that cleaves heparan sulfate (HS) side chains of proteoglycans, is involved in extracellular matrix degradation and, as such, may be involved in the atherosclerotic lesion progression. We hypothesize that heparanase is elevated in HD patients, partly due to its release from primed circulating polymorphonuclear leukocytes (PMNLs), undergoing degranulation. Priming of PMNLs was assessed by levels of CD11b and the rate of superoxide release. Heparanase mRNA expression in PMNLs was determined by RT-PCR. PMNL and plasma levels of heparanase were determined by immunoblotting, immunofluorescence, and flow cytometry analyses. The levels of soluble HS in plasma were measured by a competition ELISA. This study shows that PMNLs isolated from HD patients have higher mRNA and protein levels of heparanase compared with normal control (NC) subjects and that heparanase levels correlate positively with PMNL priming. Plasma levels of heparanase were higher in HD patients than in NC subjects and were further elevated after the dialysis session. In addition, heparanase expression inversely correlates with plasma HS levels. A pronounced expression of heparanase was found in human atherosclerotic lesions. The increased heparanase activity in the blood of HD patients results at least in part from the degranulation of primed PMNLs and may contribute to the acceleration of the atherosclerotic process. Our findings highlight primed PMNLs as a possible source for the increased heparanase in HD patients, posing heparanase as a new risk factor for cardiovascular complications and atherosclerosis.

Peripheral polymorphonuclear leukocytes (PMNL) in hemodialysis (HD) patients are primed, continually releasing and exposing the vascular endothelium to soluble factors such as reactive oxygen species and inflammatory mediators. To mimic the close proximity between PMNL and the endothelial monolayer and to monitor and characterize the influence of soluble mediators released from PMNL, we developed a novel cocultivation system using primary human umbilical vein endothelial cell (HUVEC) cultures and PMNL, with a sieve separating the two cell types to prevent direct adhesive effects. PMNL (10(6)) from HD patients or from healthy normal controls were cocultivated with HUVEC (10(5)) for 15 min, and endothelial cell injury was assessed by HUVEC morphology, cell detachment, and apoptosis. Proinflammatory changes were estimated by expression of HUVEC adhesion molecule P-selectin and by endothelial IL-8 and endothelial nitric oxide synthase mRNA. The levels of intracellular tissue factor reflected the procoagulant state, whereas NADPH oxidase activity served as an indicator for prooxidative changes in HUVEC. Mediators released from the primed PMNL triggered activation/dysfunction of endothelial cells, causing 1) an increase in endothelial cell detachment and apoptosis, 2) a proinflammatory state manifested by increased IL-8 mRNA expression and P-selectin on the endothelial surface, 3) activation of endothelial NADPH oxidase, 4) an increase in endothelial cell tissue factor that directly correlated with PMNL priming index, and 5) a decrease in endothelial nitric oxide synthase mRNA. Our data support a pathogenic link between PMNL priming and endothelial dysfunction, suggesting that PMNL priming is a potential new nontraditional risk factor for the development of atherosclerosis.

The construction, measurement, and modeling of an artificial cochlea (ACochlea) are presented in this paper. An artificial basilar membrane (ABM) was made by depositing discrete Cu beams on a piezomembrane substrate. Rather than two fluid channels, as in the mammalian cochlea, a single fluid channel was implemented on one side of the ABM, facilitating the use of a laser to detect the ABM vibration on the other side. Measurements were performed on both the ABM and the ACochlea. The measurement results on the ABM show that the longitudinal coupling on the ABM is very strong. Reduced longitudinal coupling was achieved by cutting the membrane between adjacent beams using a laser. The measured results from the ACochlea with a laser-cut ABM demonstrate cochlear-like features, including traveling waves, sharp high-frequency rolloffs, and place-specific frequency selectivity. Companion computational models of the mechanical devices were formulated and implemented using a circuit simulator. Experimental data were compared with simulation results. The simulation results from the computational models of the ABM and the ACochlea are similar to their experimental counterparts.

We present here a first report on the biochemical analysis of intestinal amyloid deposits found in two cases of hemodialysis-related amyloidosis. A new microtechnique was applied for extraction and immunochemical/chemical characterization of amyloid proteins in small amounts of fixed tissue, thus allowing precise identification of beta2microglobulin amyloid (Abeta2M) in both cases studied. The molecular mass of the identified amyloid beta2M was close to that of intact beta2M (12 kDa), with no evidence of the products of proteolytic fragmentation of these molecules. The isoelectrofocusing of the purified Abeta2M demonstrated a shift to more acidic pI as compared to the normal beta2M analyzed under the same experimental conditions. The obtained data suggest that the intestinal amyloid deposits in dialysis-related amyloidosis contain disease-specific beta2M isoforms, which could play a role in the pathogenesis of amyloid disease. The new methodology used might be useful in obtaining precise diagnosis of amyloidosis that is necessary for appropriate therapy, and also provide new important information on the chemical structure of amyloid proteins.

Background: Amyloidosis refers to a heterogeneous group of disorders associated with the deposition of chemically distinct amyloid fibril proteins. Precise determination of chemical amyloid type has diagnostic, therapeutic, and prognostic relevance. Although immunohistochemical techniques are used routinely to determine the amyloid type, the results can be negative or inconclusive, so that biochemical characterisation is often required. The development and application of new biochemical microtechniques suitable for examination of extremely small tissue samples is essential for precise identification of the deposited amyloid proteins., Aims: To investigate biochemically the amyloid proteins present in a formalin fixed paraffin wax embedded orbital tissue from a patient with localised orbital amyloidosis in whom immunohistochemistry was not helpful in the determination of amyloid type., Methods: Extraction of amyloid proteins from fixed tissue and their identification was carried out by a recently developed microtechnique. An extremely small tissue sample was dewaxed and extracted with formic acid. The extracted material was analysed using electrophoresis, western blotting, and amino acid sequencing., Results: Biochemical examination of the extracted proteins showed the presence of immunoglobulin (Ig) derived amyloid proteins, which were composed of the N-terminal fragments of the Ig light chain kappaIII subtype (AL-kappaIII) (16, 8, and 3 kDa)., Conclusions: This is the first chemically proved AL case reported in association with primary localised orbital amyloidosis. The biochemical microtechnique used was useful in achieving a precise diagnosis of amyloid disease, in a case where the results of routine immunohistochemical examination of amyloid were inconclusive.

Background: The aim of our study was to determine the accuracy and validity of frozen section analysis of endometrial curettings in differentiating between abnormal intrauterine and ectopic pregnancies., Methods: A retrospective analysis of the database of the Department of Obstetrics and Gynecology in our institute was performed from January 1998 to September 1999. In 70 women with a suspected ectopic pregnancy a diagnostic curettage was sent for frozen section examination because products of conception could not be identified macroscopically in the curettings. Routine paraffin fixation specimens were also prepared from the endometrial curettings. A frozen section diagnosis was considered correct if it concurred with the final pathologic diagnosis, and incorrect if it differed. The sensitivity, specificity, positive predictive value and negative predictive value of a frozen section in identification of conception products were calculated., Results: Of the 70 frozen section studies the diagnosis was correct in 63 (90%), and incorrect in 7 (10%) cases. Of 50 specimens interpreted as negative on frozen sections (no products of conception noted), 6 (12%) were found to contain conception products on final pathologic review. One of the 20 (5%) specimens interpreted as positive by a frozen section failed to demonstrate products of conception on a final pathologic section. The sensitivity of frozen sections in the diagnosis of ectopic pregnancy was 76%, specificity 97.8%; positive predictive value 95%; negative predictive value 88% and accuracy 90%., Conclusions: Frozen section examination is a rapid and accurate method for identifying products of conception in endometrial curettings, and may reduce delay in the diagnosis of an ectopic pregnancy and in the institution of therapy.

Objective: Juvenile (virginal) hypertrophy of the breast (JHB) is a relatively rare condition leading to gigantomastia in peripubertal females. The pathology is limited usually to the breast, with otherwise normal growth and development and without any other deformities. The rapid growth of the breast (bilateral or unilateral) in adolescent girls leads to significant physical and psychological difficulties. This gigantomastia is treated surgically by breast reduction or mastectomy and its modification. Familial JHB was described only once in the literature, and its etiology is unknown., Results: We report here on a familial pattern of juvenile hypertrophy of the breast accompanied by congenital anonychia. To the best of our knowledge, this is the first report of such a presentation. Our study dealt with four members of the same family, related through their fathers, enduring congenital anonychia of hands and feet with no functional limitation and who showed rapid uncontrolled breast enlargement in prepubertal age. This was severe enough to cause the curtailment of their social activity and cessation of schooling. The mothers of all four patients had normal breasts and nails, whereas their fathers had anonychia. The genetic basis for the association between the two clinical findings is yet to be determined., Conclusion: The four girls underwent breast reduction surgery.

A "super scan" pattern detected on bone scintigraphy usually indicates either metabolic bone disease or diffuse metastases. We report a rare case of a 45-year-old man with recurrent episodes of syncope of 10 years' duration in whom bone scintigraphy showed a super scan with an axial skeleton distribution of uptake. Bone marrow biopsy established the diagnosis of systemic mastocytosis. The few reports in the literature of super scans associated with systemic mastocytosis showed diffuse axial and appendicular increased uptake. The present case shows a super scan involving the axial skeleton, which led to the diagnosis of systemic mastocytosis.

A 41-year-old man with known Crohn's disease presented with chest pain and fever. Plain film and CT of the chest were normal, but bone scan and gallium scans showed intense sternal uptake. Surgery revealed staphylococcal osteomyelitis of the sternum. Following appropriate antibiotic treatment, the patient's symptoms resolved and follow-up gallium scans became normal. This is the first report of the association of sternal osteomyelitis and Crohn's disease, although other sites have been described. Sternal osteomyelitis has a high morbidity and the index of suspicion for this condition must be high even in the face of initially negative imaging.

The phenotypic markers of colorectal carcinomas with microsatellite instability have been widely studied and include mucinous or poor differentiation, prominent host response, a circumscribed growth pattern, histologic heterogeneity, and right-sided location. As part of a population-based case-control study of colorectal cancer in northern Israel, we reviewed the pathology and microsatellite status of 528 consecutively diagnosed colorectal cancers. Phenotypic analysis was performed by one pathologist (J.K.G.) and included assessment of grade, mucinous histology (>50%, or focal), histologic heterogeneity, growth pattern, necrosis, and host response. Microsatellite status was determined on microdissected portions of formalin-fixed, paraffin-embedded tissue using a panel of 5 NCI consensus primers. Fifty-two of 528 colorectal carcinomas were microsatellite unstable (9.85%). Multivariate analysis found that >2 tumor infiltrating lymphocytes per high power field (p <0.0001), the lack of dirty necrosis (p = 0.0054), a Crohn's-like host response (p = 0.0064), right-sided location (p = 0.032), well or poor differentiation (p = 0.037), and any mucinous differentiation (p = 0.039) were independent predictors of microsatellite instability. Tumor infiltrating lymphocytes were the single best histologic predictor of microsatellite instability. The absence of dirty necrosis and the presence of well-differentiated tumors and tumors with only focal mucinous differentiation were also important markers for microsatellite instability that have not been emphasized previously. The combination of >2 tumor infiltrating lymphocytes per high power field and/or any mucinous differentiation and/or the absence of dirty necrosis identified all MSI-H tumors in this study.

Metastatic tumors in the gastrointestinal tract are rare with an overall prevalence of 1-4 per cent in the postmortem series. Lung cancer, renal cell carcinoma, breast carcinoma and malignant melanoma are considered the most common primary tumors metastatic to the small bowel. Local duodenal metastasis from colonic cancer and cecum have been reported, but metastasis to the duodenum from rectosigmoid adenocarcinoma has not been reported before. We report the first case of metastasis in the duodenum from an adenocarcinoma of the rectum presented as a recurrent acute prerenal azotemia caused by volume depletion which had resulted from duodenal obstruction.

Leprosy is rare and non-endemic in Israel. Cases of leprosy are invariably imported by immigrants or foreign workers arriving from endemic areas. In view of the relative rarity of the disease, clinicians and pathologists are not always alert to the possibility of the disease or recognize potential symptoms. A case history is presented of a 31-year-old immigrant presenting symptoms of skin lesions and nodules on the hands and facial region, especially the ear lobe. Confirmation of the infection was provided by histopathology of suspected lesions stained for acid-fast bacilli (modified Fite-Faraco staining).

Objective: To report the occurrence of nimesulide-induced acute hepatitis confirmed by biopsy and an in vitro lymphocyte toxicity assay., Case Summary: A 54-year-old Arabic woman treated with nimesulide for chronic low back pain was admitted to the hospital with acute hepatitis confirmed by biopsy. Her liver function test results returned to normal within one month after nimesulide discontinuation. An in vitro lymphocyte toxicity assay confirmed that the liver injury was due to nimesulide exposure., Discussion: A case of acute hepatitis secondary to nimesulide, confirmed by biopsy and a laboratory in vitro assay, is described. Although the occurrence of clinically significant liver damage due to nonsteroidal antiinflammatory drugs (NSAIDs) is low, the enormous consumption of these drugs has made them an important cause of liver damage. Nimesulide, a relatively new NSAID commonly used in Europe, with a relative selectivity to cyclooxygenase type 2, can cause a wide range of liver injuries, from mild abnormal liver function to severe liver injuries. These effects are usually reversible on discontinuation of the drug, but occasionally can progress to fatal hepatic failure., Conclusions: Drug-induced acute hepatitis is a well-recognized adverse effect of many drugs, including nimesuilde. Identification of a drug as a cause for this life-threatening disease is important because the discontinuation of it may be life saving. This article confirms the occurrence of nimesulide-induced hepatitis. It also highlights the importance of monitoring liver function test results after initiating therapy with such a drug.

Background: Reactive oxygen species (ROS) play a key role in renal ischaemia-reperfusion injury. After establishing the in vitro anti-oxidative potential of mesna, a sulfhydryl-containing compound, its effect on kidney function and morphology in a rat model of ischaemic acute renal failure (ARF) was examined., Methods: Mesna (180 mg/kg) was administered at different time points relative to ischaemia and/or reperfusion onset. Kidney function was assessed by glomerular filtration rate (GFR) and fractional sodium excretion (FE(Na)) before a 45-min period of unilateral renal artery clamping and following 90 min of reperfusion. Mesna was administered by bolus, 30 min before the induction of ischaemia, 5 min before ischaemia, 5 min before reperfusion, and 5 min after the onset of reperfusion., Results: Mesna improved function of the ischaemic kidney at each administration. When mesna was administered 5 min before the onset of reperfusion, GFR reached 90-100% of its pre ischaemic value and FE(Na) was improved by 75%. The beneficial effect of mesna was also demonstrated by light and electron microscopy. Kidneys treated with mesna 5 min before reperfusion resembled ischaemic non-reperfused kidneys and showed subtle morphological and ultrastructural changes compared with ischaemic-reperfused kidneys. Mesna had no haemodynamic effect on renal blood flow and did not induce any osmotic diuresis., Conclusions: We suggest that mesna acts as an antioxidant. Its antioxidant potential together with optimal protection achieved when administered 5 min before reperfusion, supports the conclusion that mesna scavenges ROS generated at the onset of reperfusion, thus diminishing reperfusion injury and organ damage.

Thrombolytic therapy (TT) is now established as the main treatment of acute myocardial infarction (MI). Spontaneous breast hematoma, usually a rare complication of anticoagulant therapy, has been described in the last five decades, but not after thrombolytic therapy. We present three patients who developed the rare complication of breast hematoma after TT, out of 495 women treated with TT in ICCU in our hospital, because of acute MI in the last 12 years. One patient needed blood transfusion and in another patient, atypical ductal nuclei were observed in fine needle aspiration (FNA) of breast hematoma, needing further evaluation. As thrombolytic therapy becomes more widespread and essential in treating patients suffering acute occlusion of coronary, retinal, pulmonary or peripheral arteries, it is expected that more women will present with breast hematoma following such treatment.

Mucosa-associated lymphoid tissue (MALT) lymphomas arise in most cases in the gastrointestinal tract, and are usually of low-grade B cell origin. MALT lymphomas may rarely occur in organs where lymphoid tissue is sparse, especially following inflammatory conditions. Primary lymphomas of the gallbladder are extremely rare, and MALT lymphoma has been reported only twice. We herein describe the third case of low-grade MALT lymphoma of the gallbladder, which exhibits an unusual clinical behavior. The exceptionally advanced stage of the disease stresses the importance of early operation when cholecystectomy is indicated.

Dermatofibrosarcoma protuberans is an uncommon skin tumor with a high potential for local recurrence if not adequately excised. There are only two reports in the literature describing dermatofibrosarcoma protuberans that enlarged considerably during pregnancy. On the other hand, the new development or enlargement of dermatofibromas in pregnancy is well documented. We present 2 additional patients in whom a dermatofibrosarcoma protuberans appeared and grew rapidly during pregnancy. Immunohistochemical studies were negative for estrogen and progesterone receptors. The possible pathophysiology and surgical management are presented and discussed.

Single optic tract fibers in the cat were classified as X or Y cells by a contrast reversal stimulus. A slit of light was then moved across the receptive field at velocities from 10--1000 degrees/s. The preferred velocity was that velocity which elicited the strongest response from the cell. The maximum velocity was the highest velocity target to which a cell could respond. Y cells as a group both preferred and could follow faster targets than X cells, and were more broadly tuned to the preferrred velocity.

A comparison was made between adaptive and signal sensitivity profiles of the surround response mechanism of cat retinal ganglion cells. The 2 profiles were found to be similar for X cells but the surrounds of Y cells appear to pool adaptation over a smaller retinal region than they pool signals.

The summing properties of the surround response mechanism of cat retinal ganglion cells were assessed by determining area-sensitivty and area-adaptation curves. The two curves were found to be similar for X and Y cells but for many Y cells adaptive sensitivity was found to be dependent upon the size of the test target. These results suggest that, for X cells, the retinal area over which the surround integrates signals and adaptation are spatially coextensive. Most Y cells appear to pool adaptive effects over a smaller region than they pool signals.

We ascertained prior pulmonary tuberculosis infection in 211 non-Caucasian female lung cancer patients and 419 sex, race, ape, smoking history and birthplace-matched control subjects by searching the Hawaii State Tuberculosis Branch patient records. Among never-smokers we found a significant increase in risk associated with prior tuberculous infection (odds ratio, 8.2; 95% confidence limits = 1.3 to 54.4). No such association was found among smokers. Prior tuberculous infection was identified in only 5.5% of never-smoking lung cancer patients, however, suggesting that this factor is a relatively unimportant contributor to the etiologic aspects of lung cancer in persons who have never smoked.

Signal and adaptive sensitivity profiles of the surrounds of cat retinal ganglion cells were determined by varying the position of concentric annuli whose outside and inside diameters varied but whose total area remained constant. Signal sensitivity profiles were determined by adjusting the luminances of these annuli so as to produce a weak suprathreshold response of constant magnitude and time course. Adaptive sensitivity profiles were determined by varying the luminances of concentric equal-area, unmodulated annuli until the response to a temporally modulated annulus attained a criterion level. The results provided evidence that the retinal region over which the surround mechanism of an X cell pools adaptive information and pools signals are the same, and that the distribution of adaptive and signal sensitivities within these regions is similar. A small number of X cells showed local adaptation effects. The adaptive pooling area appeared to be smaller than the signal pooling area for Y cells.