In vitro anti-leukemia, antioxidant, and anti-inflammatory properties of Lantana camara.

It has been demonstrated that Lantana camara possesses several therapeutic properties that can be used to treat various human diseases, including dermatological and gastrointestinal conditions, tetanus, malaria, and tumours. In this investigation, every collected part of L. camara was extracted with absolute methanol to examine its antioxidant capacity using the DPPH assay and its anti-leukemia activity on two AML cell lines, MOLM-13 and MV4-11. In addition, anti-inflammatory effectiveness was evaluated. The results show that extracts from various sections of L. camara have a significant ability to neutralize free radicals, as indicated by their EC50 values. Most of the extracts had values less than 100 µg/ml, with the flower extract having an even lower value of less than 50 µg/ml. Experiments on two AML cell lines showed that the anti-leukemia effects of the extracts were remarkable, with the most potent impact belonging to the root extract (IC50 was 9.78 ± 0.61 and 12.48 ± 1.69 for MOLM-13 and MV4-11 cell lines). The antitumor effect of the extracts was determined to be time- and dose-dependent and did not correlate with antioxidant capacity. Furthermore, when BJ cells were exposed to L. camara root and leaf extracts, their migratory potential was dramatically reduced compared to untreated cells. The extracts demonstrated potential anti-inflammatory capabilities by lowering NO production in LPS-induced BJ cells.

Simultaneously Both Expression of LMP-1 and Methylation of E-cadherin: Molecular Biomarker in Stage IV of Nasopharyngeal Carcinoma Patients.

The phenome of E-cadherin gene methylation and the expression of latent membrane protein 1 (LMP-1) gene are associated with nasopharyngeal carcinoma (NPC). In order to determine whether cooperative LMP-1 expression or methylation of E-cadherin could serve as the potential molecule biomarker target for diagnosis and therapy of NPC, a case-control study including 93 NPC biopsy samples and 100 non cancerous nasopharyngeal swab samples were examined, as well as the strength of association among them by the quantitative polymerase chain reaction (qPCR) and nested-methylation-specific PCR methods. The significantly higher frequency of LMP-1 expression and E-cadherin methylation in NPC biopsy samples, accounting for 76.34 and 73.12%, respectively, compared to non cancerous samples, accounting for 0.00 and 30.00%, respectively, were observed. The significant correlation between the LMP-1 expression and E-cadherin methylation in NPC samples was reported. In detail, in the stage IV of NPC, in case of LMP-1-positive samples, 35 of 37 samples (accounting for 94.60%) were positive for methylation of E-cadherin. It was demonstrated that cooperative LMP-1 expression and E-cadherin gene methylation could serve as a molecular biomarker in NPC.

Autologous bilayered self-assembled skin substitutes (SASSs) as permanent grafts: a case series of 14 severely burned patients indicating clinical effectiveness.

Split-thickness skin autografts (AGs) are the standard surgical treatment for severe burn injuries. However, the treatment of patients with substantial skin loss is limited by the availability of donor sites for skin harvesting. As an alternative to skin autografts, our research group developed autologous self-assembled skin substitutes (SASSs), allowing the replacement of both dermis and epidermis in a single surgical procedure. The aim of the study was to assess the clinical outcome of the SASSs as a permanent coverage for full-thickness burn wounds. Patients were recruited through the Health Canada's Special Access Program. SASSs were grafted on debrided full-thickness wounds according to similar protocols used for AGs. The graft-take and the persistence of the SASS epithelium over time were evaluated. 14 patients received surgical care with SASSs. The mean percentage of the SASS graft-take was 98 % (standard deviation = 5) at 5 to 7 d after surgery. SASS integrity persisted over time (average follow-up time: 3.2 years), without noticeable deficiency in epidermal regeneration. Assessment of scar quality (skin elasticity, erythema, thickness) was performed on a subset of patients. Non-homogeneous pigmentation was noticed in several patients. These results indicated that the SASS allowed the successful coverage of full-thickness burns given its high graft-take, aesthetic outcome equivalent to autografting and the promotion of long-term tissue regeneration. When skin donor sites are in short supply, SASSs could be a valuable alternative to treat patients with full-thickness burns covering more than 50 % of their total body surface area.

Hsp90 chaperones PPARγ and regulates differentiation and survival of 3T3-L1 adipocytes.

Adipose tissue dysregulation has a major role in various human diseases. The peroxisome proliferator-activated receptor-γ (PPARγ) is a key regulator of adipocyte differentiation and function, as well as a target of insulin-sensitizing drugs. The Hsp90 chaperone stabilizes a diverse set of signaling 'client' proteins, thereby regulates various biological processes. Here we report a novel role for Hsp90 in controlling PPARγ stability and cellular differentiation. Specifically, we show that the Hsp90 inhibitors geldanamycin and novobiocin efficiently impede the differentiation of murine 3T3-L1 preadipocytes. Geldanamycin at higher concentrations also inhibits the survival of both developing and mature adipocytes, respectively. Further, Hsp90 inhibition disrupts an Hsp90-PPARγ complex, leads to the destabilization and proteasomal degradation of PPARγ, and inhibits the expression of PPARγ target genes, identifying PPARγ as an Hsp90 client. A similar destabilization of PPARγ and a halt of adipogenesis also occur in response to protein denaturing stresses caused by a single transient heat-shock or proteasome inhibition. Recovery from stress restores PPARγ stability and adipocyte differentiation. Thus, our findings reveal Hsp90 as a critical stress-responsive regulator of adipocyte biology and offer a potential therapeutic target in obesity and the metabolic syndrome.

The report of male gender and retinopathy status improves the current consensus guidelines for the screening of myocardial ischemia in asymptomatic type 2 diabetic patients.

BACKGROUND AND AIMS: American Diabetes Association (ADA), French-speaking Societies for diabetes & cardiology (ALFEDIAM-SFC) and Cardiac Radionuclide Imaging (CRI) have proposed guidelines for the screening of silent myocardial ischemia (SMI). The aim of the study was to evaluate their diagnostic values and how to improve them. METHODS AND RESULTS: 731 consecutive type 2 diabetic patients with ≥1 additional risk factor were screened between 1992 and 2006 for SMI by stress myocardial scintigraphy and for silent coronary artery disease (CAD) by coronary angiography. A total of 215 (29.4%) patients had SMI, and 79 of them had CAD. ADA (Odds Ratio 1.7 [95% Confidence Interval: 1.2-2.5]; p < 0.05), ALFEDIAM-SFC (OR 1.5 [1.0-2.5], p < 0.05) and CRI criteria (OR 2.0 [1.4-2.8], p < 0.01) predicted SMI. Considering the presence of male gender and retinopathy added to the prediction of SMI allowed by ADA criteria (c statistic: area under the curve AROC 0.651 [0.605-0.697] versus 0.582 [0.534-0.630]), p < 0.01 and ALFEDIAM-SFC criteria (AROC 0.672 [0.620-0.719] versus 0.620 [0.571-0.670], p < 0.05). CRI prediction of SMI was improved by considering the presence of macroproteinuria and retinopathy (AROC 0.621 [0.575-0.667] versus 0.594 [0.548-0.641], p < 0.01). Severe retinopathy (OR 3.4 [1.2-9.4], p < 0.05), smoking habits (OR 2.1 [1.1-4.2], p < 0.05) and triglyceride levels (OR 1.3 [1.0-1.6], p < 0.05) were independent predictors of CAD in the patients with SMI. CONCLUSION: Current guidelines criteria are able to predict SMI but prediction may be improved by considering male gender and the presence of retinopathy. CAD is more frequent in the patients with SMI who are current smokers, have severe retinopathy and higher triglyceride levels.

Regulation of chemokine and chemokine receptor expression by PPARγ in adipocytes and macrophages.

BACKGROUND: PPARγ plays a key role in adipocyte biology, and Rosiglitazone (Rosi), a thiazolidinedione (TZD)/PPARγ agonist, is a potent insulin-sensitizing agent. Recent evidences demonstrate that adipose tissue inflammation links obesity with insulin resistance and that the insulin-sensitizing effects of TZDs result, in part, from their anti-inflammatory properties. However the underlying mechanisms are unclear. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we establish a link between free fatty acids (FFAs) and PPARγ in the context of obesity-associated inflammation. We show that treatment of adipocytes with FFAs, in particular Arachidonic Acid (ARA), downregulates PPARγ protein and mRNA levels. Furthermore, we demonstrate that the downregulation of PPARγ by ARA requires the activation the of Endoplamsic Reticulum (ER) stress by the TLR4 pathway. Knockdown of adipocyte PPARγ resulted in upregulation of MCP1 gene expression and secretion, leading to enhanced macrophage chemotaxis. Rosi inhibited these effects. In a high fat feeding mouse model, we show that Rosi treatment decreases recruitment of proinflammatory macrophages to epididymal fat. This correlates with decreased chemokine and decreased chemokine receptor expression in adipocytes and macrophages, respectively. CONCLUSIONS AND SIGNIFICANCE: In summary, we describe a novel link between FAs, the TLR4/ER stress pathway and PPARγ, and adipocyte-driven recruitment of macrophages. We thus both describe an additional potential mechanism for the anti-inflammatory and insulin-sensitizing actions of TZDs and an additional detrimental property associated with the activation of the TLR4 pathway by FA.

What would be the outcome if the American Diabetes Association recommendations of 2010 had been followed in our practice in 1998-2006?

AIMS: In 2010, the American Diabetes Association has published recommendations on the population to be screened for dysglycaemia; the diagnostic criteria for intermediate hyperglycaemia and diabetes using oral glucose tolerance testing and HbA(1c); and the patients eligible for treatment with metformin. We aimed to evaluate the consequences of screening with oral glucose tolerance test or HbA(1c) in an at-risk population. METHODS: Among 1177 overweight or obese consecutive adults without known diabetes who were referred to our department for weight management, we selected 1157 individuals (83% female; 80% European) fulfilling the American Diabetes Association 2010 criteria for dysglycaemia screening. RESULTS: Mean age was 41.2 ± 13 years, BMI 37.0 ± 7.2 kg/m(2), fasting plasma glucose 4.9 ± 0.8 mmol/l and HbA(1c) (turbidimetric immunoassay) 5.7 ± 0.7% (39 mmol/mol). Based on oral glucose tolerance test and HbA(1c), respectively, 76 (6.6%) and 113 (9.8%) patients had diabetes, including 34 sharing both criteria; 307 (26.5%) and 478 (41.3%) had intermediate hyperglycaemia; and 130 (11.2%) and 255 (22.0%) would be treated with metformin. The sensitivity/specificity of HbA(1c) ≥ 6.5% (48 mmol/mol) for the diagnosis of diabetes according to the oral glucose tolerance test were 44.7/92.7%. Diabetes risk scores and UK Prospective Diabetes Study cardiovascular risk score were the highest in the 130 patients having both an abnormal oral glucose tolerance test and HbA(1c) ≥ 5.7%. CONCLUSIONS: In a population at risk for diabetes, the HbA(1c) strategy could lead to diagnosing more cases of dysglycaemia and to treating more patients with metformin than the oral glucose tolerance test strategy. The consistency of either diagnostic criteria was low. The patients with the highest a priori risk of diabetes and cardiovascular disease were those fulfilling both oral glucose tolerance test and HbA(1c) criteria.

Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice.

Obesity represents a state of chronic, low grade inflammation and is associated with infiltration of increased numbers of adipose tissue macrophages (ATMs). Diet-induced obesity leads to an increase in non-inflammatory M1-like ATMs displaying the CD11c surface marker. We assessed the function of CD11c-positive ATMs when insulin resistant high fat diet (HFD) mice become insulin-sensitive after switching from HFD to normal chow (NC). HFD mice rapidly become insulin-sensitive in all major insulin-target tissues, including muscle, liver, and adipose tissue, after the diet switch. In adipose tissue the CD11c-positive macrophages remain constant in number despite the presence of insulin sensitivity, but these macrophages now assume a new phenotype in which they no longer exhibit increased inflammatory pathway markers. Adipose tissue markers of apoptosis and necrosis were elevated on HFD and remain high after the HFD --> NC diet switch. Furthermore, ATM accumulation preceded detectable adipocyte necrosis at the early phase of HFD. Together, these results indicate that 1) CD11c-positive M1-like ATMs can exhibit phenotypic plasticity and that the polarization of these cells between inflammatory and non-inflammatory states is well correlated to the presence of absence of insulin resistance, and 2) adipocyte necrosis and apoptosis can be dissociated from ATM accumulation.

Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERalpha-deficient mice.

Impaired estrogen action is associated with the metabolic syndrome in humans. We sought to determine whether impaired estrogen action in female C57Bl6 mice, produced by whole body Esr1 ablation, could recapitulate aspects of this syndrome, including inflammation, insulin resistance, and obesity. Indeed, we found that global knockout (KO) of the estrogen receptor (ER)alpha leads to reduced oxygen uptake and caloric expenditure compared with wild-type (WT) mice. In addition, fasting insulin, leptin, and PAI-1 levels were markedly elevated, whereas adiponectin levels were reduced in normal chow-fed KO. Furthermore, ERalpha-KO mice exhibited impaired glucose tolerance and marked skeletal muscle insulin resistance that was accompanied by the accumulation of bioactive lipid intermediates, inflammation, and diminished PPARalpha, PPARdelta, and UCP2 transcript levels. Although the relative glucose intolerance and insulin resistance phenotype in KO mice became more severe with high-fat feeding, WT mice were refractory to these dietary-induced effects, and this protection coincided with a marked increase in circulating adiponectin and heat shock protein 72 levels in muscle, liver, and fat. These data indicate that ERalpha is critical for the maintenance of whole body insulin action and protection against tissue inflammation during both normal chow and high-fat feeding.

Transporters in drug-refractory epilepsy: clinical significance.

Drug resistance remains an unmet challenge in a variety of neurological disorders, but epilepsy is probably the refractory disease that has received most experimental, preclinical, and therapeutic attention. Although resective surgery continues to improve our ability to provide seizure relief, new discoveries have potential as alternative therapeutic approaches to multiple drug resistance. As discussed here, the field is replete with controversies and false starts, in particular as it concerns the existence of genetic predisposition to inadequate pharmacological seizure control.

Glucocorticoids and thiazolidinediones interfere with adipocyte-mediated macrophage chemotaxis and recruitment.

The link between intra-abdominal adiposity and type II diabetes has been known for decades, and adipose tissue macrophage (ATM)-associated inflammation has recently been linked to insulin resistance. However, the mechanisms associated with ATM recruitment remain ill defined. Herein, we describe in vitro chemotaxis studies, in which adipocyte conditioned medium was used to stimulate macrophage migration. We demonstrate that tumor necrosis factor alpha and free fatty acids, key inflammatory stimuli involved in obesity-associated autocrine/paracrine inflammatory signaling, stimulate adipocyte expression and secretion of macrophage chemoattractants. Pharmacological studies showed that peroxisome proliferator-activated receptor gamma agonists and glucocorticoids potently inhibit adipocyte- induced recruitment of macrophages. This latter effect was mediated by the glucocorticoid receptor, which led to decreased chemokine secretion and expression. In vivo results were quite comparable; treatment of high fat diet-fed mice with dexamethasone prevented ATM accumulation in epididymal fat. This decrease in ATM was most pronounced for the proinflammatory F4/80(+), CD11b(+), CD11c(+) M-1-like ATM subset. Overall, our results elucidate a beneficial function of peroxisome proliferator-activated receptor gamma activation and glucocorticoid receptor/glucocorticoids in adipose tissue and indicate that pharmacologic prevention of ATM accumulation could be beneficial.

A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways.

Obesity and type 2 diabetes are characterized by decreased insulin sensitivity, elevated concentrations of free fatty acids (FFAs), and increased macrophage infiltration in adipose tissue (AT). Here, we show that FFAs can cause activation of RAW264.7 cells primarily via the JNK signaling cascade and that TLR2 and TLR4 are upstream of JNK and help transduce FFA proinflammatory signals. We also demonstrate that F4/80(+)CD11b(+)CD11c(+) bone marrow-derived dendritic cells (BMDCs) have heightened proinflammatory activity compared with F4/80(+)CD11b(+)CD11c(-) bone marrow-derived macrophages and that the proinflammatory activity and JNK phosphorylation of BMDCs, but not bone marrow-derived macrophages, was further increased by FFA treatment. F4/80(+)CD11b(+)CD11c(+) cells were found in AT, and the proportion and number of these cells in AT is increased in ob/ob mice and by feeding wild type mice a high fat diet for 1 and 12 weeks. AT F4/80(+)CD11b(+)CD11c(+) cells express increased inflammatory markers compared with F4/80(+)CD11b(+)CD11c(-) cells, and FFA treatment increased inflammatory responses in these cells. In addition, we found that CD11c expression is increased in skeletal muscle of high fat diet-fed mice and that conditioned medium from FFA-treated wild type BMDCs, but not TLR2/4 DKO BMDCs, can induce insulin resistance in L6 myotubes. Together our results show that FFAs can activate CD11c(+) myeloid proinflammatory cells via TLR2/4 and JNK signaling pathways, thereby promoting inflammation and subsequent cellular insulin resistance.

Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones.

PPAR gamma is required for fat cell development and is the molecular target of antidiabetic thiazolidinediones (TZDs), which exert insulin-sensitizing effects in adipose tissue, skeletal muscle, and liver. Unexpectedly, we found that inactivation of PPAR gamma in macrophages results in the development of significant glucose intolerance plus skeletal muscle and hepatic insulin resistance in lean mice fed a normal diet. This phenotype was associated with increased expression of inflammatory markers and impaired insulin signaling in adipose tissue, muscle, and liver. PPAR gamma-deficient macrophages secreted elevated levels of factors that impair insulin responsiveness in muscle cells in a manner that was enhanced by exposure to FFAs. Consistent with this, the relative degree of insulin resistance became more severe in mice lacking macrophage PPAR gamma following high-fat feeding, and these mice were only partially responsive to TZD treatment. These findings reveal an essential role of PPAR gamma in macrophages for the maintenance of whole-body insulin action and in mediating the antidiabetic actions of TZDs.

JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes.

Lipid infusion and high fat feeding are established causes of systemic and adipose tissue insulin resistance. In this study, we treated 3T3-L1 adipocytes with a mixture of free fatty acids (FFAs) to investigate the molecular mechanisms underlying fat-induced insulin resistance. FFA treatment impaired insulin receptor-mediated signal transduction and decreased insulin-stimulated GLUT4 translocation and glucose transport. FFAs activated the stress/inflammatory kinases c-Jun N-terminal kinase (JNK) and IKKbeta, and the suppressor of cytokine signaling protein 3, increased secretion of the inflammatory cytokine tumor necrosis factor (TNF)-alpha, and decreased secretion of adiponectin into the medium. RNA interference-mediated down-regulation of JNK blocked JNK activation and prevented most of the FFA-induced defects in insulin action. Blockade of TNF-alpha signaling with neutralizing antibodies to TNF-alpha or its receptors or with a dominant negative TNF-alpha peptide had a partial effect to inhibit FFA-induced cellular insulin resistance. We found that JNK activation by FFAs was not inhibited by blocking TNF-alpha signaling, whereas the FFA-induced increase in TNF-alpha secretion was inhibited by RNA interference-mediated JNK knockdown. Together, these results indicate that 1) JNK can be activated by FFAs through TNF-alpha-independent mechanisms, 2) activated JNK is a major contributor to FFA-induced cellular insulin resistance, and 3) TNF-alpha is an autocrine/paracrine downstream effector of activated JNK that can also mediate insulin resistance.

Adenovirus-mediated adiponectin expression augments skeletal muscle insulin sensitivity in male Wistar rats.

In this study, we investigated the chronic in vivo effect of adiponectin on insulin sensitivity and glucose metabolism by overexpressing the adiponectin protein in male Wistar rats using intravenous administration of an adenovirus (Adv-Adipo). Virally infected liver secreted adiponectin as high and low molecular weight complexes. After 7 days of physiological or supraphysiological hyperadiponectinemia, the animals displayed enhanced insulin sensitivity during the glucose tolerance and insulin tolerance tests. Glucose clamp studies performed at submaximal and maximal insulin infusion rates (4 and 25 mU x kg(-1) x min(-1), respectively) also demonstrated increased insulin sensitivity in Adv-Adipo animals, with the insulin-stimulated glucose disposal rate being increased by 20-67%. In contrast, insulin's effect on the suppression of hepatic glucose output and plasma free fatty acid levels was not enhanced in Adv-Adipo rats compared with controls, suggesting that high levels of adiponectin expression in the liver may lead to a local desensitization. Consistent with the clamp data, the activation of AMP-activated protein kinase was significantly enhanced in skeletal muscle (by 50%) but not in liver. One interesting finding was that in male Wistar rats, both AdipoR1 and AdipoR2 expression levels were higher in skeletal muscle than in liver, as it is the case in humans. These results indicate that chronic adiponectin treatment enhances insulin sensitivity and could serve as a therapy for human insulin resistance.

Adenovirus-mediated chronic "hyper-resistinemia" leads to in vivo insulin resistance in normal rats.

We investigated the chronic in vivo effect of resistin on insulin sensitivity and glucose metabolism by overexpressing resistin protein in male Wistar rats using intravenous administration of an adenovirus encoding mouse resistin. After 7 days of elevated resistin levels at a supraphysiological concentration, the animals displayed glucose intolerance and hyperinsulinemia during glucose tolerance tests, and insulin tolerance tests demonstrated an impaired glucose-lowering effect of insulin. The glucose clamp studies were performed at submaximal (4 mU/kg/min) and maximal (25 mU/kg/min) insulin infusion rates and demonstrated the presence of insulin resistance induced by elevated resistin levels. Indeed, the insulin-stimulated glucose infusion rate was decreased by 12-31%; suppression of hepatic glucose output was attenuated by 28-55%; and insulin suppression of circulating FFA levels was inhibited by 7%. Insulin receptor substrate-1 and -2 phosphorylation and Akt activation were impaired in muscle and adipose tissue. Interestingly, activation of AMP-activated protein kinase in skeletal muscle, liver, and adipose tissue was also significantly downregulated. Together, these results indicate that chronic "hyper-resistinemia" leads to whole-body insulin resistance involving impaired insulin signaling in skeletal muscle, liver, and adipose tissue, resulting in glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. Thus elevated resistin levels in normal rats fed a regular chow diet produce many of the features of human syndrome X.

Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse.

Production of prostaglandin E(2) (PGE(2)) is enhanced during inflammation, and this lipid mediator can dramatically modulate immune responses. There are four receptors for PGE(2) (EP1-EP4) with unique patterns of expression and different coupling to intracellular signaling pathways. To identify the EP receptors that regulate cellular immune responses, we used mouse lines in which the genes encoding each of the four EP receptors were disrupted by gene targeting. Using the mixed lymphocyte response (MLR) as a model cellular immune response, we confirmed that PGE(2) has potent antiproliferative effects on wild-type responder cells. The absence of either the EP1 or EP3 receptors did not alter the inhibitory response to PGE(2) in the MLR. In contrast, when responder cells lacked the EP2 receptor, PGE(2) had little effect on proliferation. Modest resistance to PGE(2) was also observed in EP4-/- responder cells. Reconstitution experiments suggest that EP2 receptors primarily inhibit the MLR through direct actions on T cells. Furthermore, PGE(2) modulates macrophage function by activating the EP4 receptor and thereby inhibiting cytokine release. Thus, PGE(2) regulates cellular immune responses through distinct EP receptors on different immune cell populations: EP2 receptors directly inhibit T cell proliferation while EP2 and EP4 receptors regulate antigen presenting cells functions.

Magnification views of mammography decrease biopsy rates.

Mammography is a valuable tool for screening and has increased early detection of breast cancer. Magnification views are commonly used to further elucidate suspicious changes seen on routine mammograms. The effect of magnification views and their utility have not been studied regarding the influence on treatment strategies. All patients who had magnification views performed along with their mammogram at Tulane University Medical Center over a one-year period were included. Patient charts were reviewed for mammogram readings, recommendations, and any biopsy results. The original mammograms without the magnification views were given to a physician who was blinded to the final results of the magnification views for a recommendation of whether or not to biopsy the lesion. These recommendations were compared with the results with actual recommendations. Magnification views were performed on 127 patients. After the additional magnification views were taken 27 per cent (34 of 127) of patients had biopsies performed. Biopsy results revealed benign findings in 71 per cent and nonbenign findings (lobular carcinoma in situ, ductal carcinoma in situ, or carcinoma) in 29 per cent. On the basis of the recommendations without magnification views 64 per cent of patients would have had biopsies performed. Magnification views decreased the biopsy rates by 58 per cent (P < 0.001; chi2 tests). Magnification views can help decrease the number of biopsies performed for suspicious small areas on mammograms. Their judicious use can help decrease unnecessary procedures, patient anxiety, and cost. Magnification views are useful to help surgeons and radiologists best screen for breast cancer.

Siderotic nodules in the cirrhotic liver at MR imaging with explant correlation: no increased frequency of dysplastic nodules and hepatocellular carcinoma.

PURPOSE: To determine the sensitivity of magnetic resonance (MR) imaging for detection of siderotic nodules in patients with cirrhosis and whether the frequency of hepatocellular carcinoma (HCC) and dysplastic nodules is greater if siderotic nodules are present. MATERIALS AND METHODS: MR imaging (1.5 T) was performed within 0-117 days (mean, 30 days) before liver transplantation in 77 patients. Two readers retrospectively evaluated gradient-echo (GRE) (echo time [TE], > or = 9 and 4-5 msec) and turbo short inversion time inversion-recovery or T2-weighted images for low-signal-intensity nodules. Whole-explant pathologic correlation was available in every case. RESULTS: At explantation, 28 (36%) of 77 patients had HCC, 25 (32%) had dysplastic nodules, and nine (12%) had both; 35 (45%) patients had siderotic nodules. The sensitivity of GRE imaging with 9-msec or longer TE for the detection of siderotic nodules was 80% (28 of 35) but decreased to 31% (11 of 35) with 4-5-msec TE. Frequency of HCC was not significantly higher (P =.27) in patients with (43% [15 of 35]) than in patients without (31% [13 of 42]) siderotic nodules. Frequency of dysplastic nodules also was not significantly higher (P =.42) in patients with (37% [13 of 35]) than in patients without (29% [12 of 42]) siderotic nodules. CONCLUSION: Sensitivity of MR imaging for the detection of siderotic nodules was improved with use of GRE pulse sequences with longer TEs of 9 msec or greater (80%) versus 4-5 msec (31%); however, there was no significant increased frequency of HCC or dysplastic nodules in patients with pathologically proved siderotic nodules.

Siderotic nodules at MR imaging: regenerative or dysplastic?

OBJECTIVE: To determine if iron containing "siderotic" nodules detected at magnetic resonance (MR) imaging are regenerative (RN) or dysplastic (DN) and to attempt to identify features that may distinguish them. MATERIAL AND METHODS: MR imaging (1.5 T) was performed on 77 cirrhotic patients who underwent orthotopic liver transplantation within 0-117 days (mean 30 days) of MR imaging. Two readers retrospectively evaluated breath-hold gradient-echo pulse sequences (echo time > or =9.0 ms, flip angle < or =45 degrees) for the presence of hypointense nodules, which were classified as micronodular (< or =3 mm), macronodular (>3 mm), or mixed. Nodule distribution was classified as focal (<5), scattered (5-20), or diffuse (>20) per slice. Thin section pathologic correlation was available in all cases, and Prussian blue iron stains were performed. RESULTS: Of 35 patients with pathologically proven siderotic nodules, 10 (29%) had at least 2 siderotic DN. MR detected siderotic nodules in 10 of 10 (100%) patients with siderotic DN and RN, and in 18 of 25 patients (72%) with siderotic RN only. CONCLUSION: Siderotic RN cannot be reliably distinguished from siderotic DN with MR imaging, and therefore the widely used term "siderotic regenerative nodule" should be avoided and replaced by "siderotic nodule."