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Cardiac sympathetic denervation (CSD) to treat ventricular arrhythmias (VAs) requires transection at the middle or lower third of stellate (cervicothoracic) ganglia (SG). However, the morphological appearance of the adult SG and distribution of neuronal somata within it are not well described. To determine the morphology of left and right SG (LSG and RSG) and the distribution of somata within. LSG and RSG (n = 28) from 14 embalmed adult cadavers were dissected intact. Weight, volume, height, morphologic appearance, relationship between C8 and T1 ganglia (which form the SG) were determined, along with histology. Demographics, history of cardiac disease, and cause of death were also reviewed. Mean age of the subjects was 76 ± 13 years, and 5/14 were male. Three distinct morphologies of SG were identified: fusiform-rounded; fusiform-elongated; and bilobed. RSG and LSG did not differ in weight or volume. RSG were longer than LSG (2.05 ± 0.28 cm vs. 1.66 ± 0.47 cm, P = 0.024). Bilobed morphology was most common in RSGs (8/14), while fused, elongated was most common in LSG (8/14). RSGs lacked fused, rounded appearance, while 28.6% of LSG appeared as such. Histologically, one focus of somata was seen in fused rounded ganglia, while fused elongated SG had somata distributed throughout. Bilobed SG demonstrated two foci of somata, with the interconnecting stalk containing sparse somata. SG appears in three major forms and contains varying distributions of somata. Larger studies are warranted to define the relationship between gross anatomy and distribution of neuronal somata to improve the efficacy of CSD in treating VAs. Anat Rec, 301:1244-1250, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70-101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI - 34-72) and the median time to progression was 43 months (95% CI - 22-64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival (p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

25-Hydroxycholesterol (25OHC) is an enzymatically derived oxidation product of cholesterol that modulates lipid metabolism and immunity. 25OHC is synthesized in response to interferons and exerts broad antiviral activity by as yet poorly characterized mechanisms. To gain further insights into the basis for antiviral activity, we evaluated time-dependent responses of the macrophage lipidome and transcriptome to 25OHC treatment. In addition to altering specific aspects of cholesterol and sphingolipid metabolism, we found that 25OHC activates integrated stress response (ISR) genes and reprograms protein translation. Effects of 25OHC on ISR gene expression were independent of liver X receptors and sterol-response element-binding proteins and instead primarily resulted from activation of the GCN2/eIF2α/ATF4 branch of the ISR pathway. These studies reveal that 25OHC activates the integrated stress response, which may contribute to its antiviral activity.

Macrophage-mediated inflammation is a major contributor to obesity-associated insulin resistance. The corepressor NCoR interacts with inflammatory pathway genes in macrophages, suggesting that its removal would result in increased activity of inflammatory responses. Surprisingly, we find that macrophage-specific deletion of NCoR instead results in an anti-inflammatory phenotype along with robust systemic insulin sensitization in obese mice. We present evidence that derepression of LXRs contributes to this paradoxical anti-inflammatory phenotype by causing increased expression of genes that direct biosynthesis of palmitoleic acid and ω3 fatty acids. Remarkably, the increased ω3 fatty acid levels primarily inhibit NF-κB-dependent inflammatory responses by uncoupling NF-κB binding and enhancer/promoter histone acetylation from subsequent steps required for proinflammatory gene activation. This provides a mechanism for the in vivo anti-inflammatory insulin-sensitive phenotype observed in mice with macrophage-specific deletion of NCoR. Therapeutic methods to harness this mechanism could lead to a new approach to insulin-sensitizing therapies., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Two variants of the fibularis (peroneus) quartus muscle were identified and photographed in the legs of a 70-year-old white male cadaver. A rare peroneocuboideus (fibulocuboideus) muscle (as described by Chudzinski) and a novel peroneocalcaneocuboideus (fibulocalcaneocuboideus) muscle was found in the right and left leg, respectively. The latter muscle has not been previously reported and was termed "peroneocalcaneocuboideus" on the basis of its origin and insertions. Also, the distal attachment of both muscles inserted onto the distal lip of the peroneal sulcus of the cuboid bone, which differs from the historical data. The insertion of the peroneocuboideus muscle was previously described as being at the tuberosity of the cuboid bone or, simply, the lateral surface of the cuboid. Therefore, the present case study provides the first gross anatomic photographs of these variant leg muscles along their entire length, identifies a novel fibularis quartus variant, and describes a new insertion site for the peroneocuboideus muscle. Throughout our report, the historical data are reviewed to list the prevalence and describe the clinical implications of the fibularis quartus muscle and its variants. The presence of variant fibularis quartus muscles has been known to cause lateral ankle pain and stenosis, ankle instability, fibular tenosynovitis, subluxation of the fibular (peroneal) tendons, and longitudinal splitting of the fibularis brevis tendon in radiologic and case studies. Therefore, surgeons, radiologists, and clinicians should be aware of these variant muscles when considering various diagnoses, interpreting radiographs, and pursuing surgical intervention to relieve lateral ankle pathologic features., (Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

The sural nerve is at risk of iatrogenic injury even during minimally invasive operative procedures to repair the calcaneal (Achilles) tendon. Through 107 cadaveric leg dissections, the data derived from the present study was used to develop a regression equation that will enable surgeons to estimate the intersection point at which the sural nerve crosses the lateral border of the Achilles tendon, an important surgical landmark. In most cases, the sural nerve crossed the lateral border of the Achilles tendon 8 to 10 cm proximal to the superior border of the calcaneal tuberosity. By simply measuring the leg length of the patient (from the base of the heel to the flexor crease of the popliteal fossa), surgeons can approximate the location of this intersection point with an interval length of 0.68 to 1.80 cm, with 90% confidence, or 0.82 to 2.15 cm, with 95% confidence. For example, for a patient with a lower leg length of 47.0 cm, the mean measurement in the present study, a surgeon can be 90% confident that the sural nerve will cross the lateral border of the Achilles tendon 8.28 to 8.96 cm (interval width of 0.68 cm) proximal to the calcaneal tuberosity. Currently, ultrasound and clinical techniques have been implemented to approximate the location of the sural nerve. The results of the present study offer surgeons another method, that is less intensive, to locate reliably and subsequently avoid damage to the sural nerve during calcaneal (Achilles) tendon repair and other procedures of the posterolateral leg and ankle., (Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Inflammation and macrophage foam cells are characteristic features of atherosclerotic lesions, but the mechanisms linking cholesterol accumulation to inflammation and LXR-dependent response pathways are poorly understood. To investigate this relationship, we utilized lipidomic and transcriptomic methods to evaluate the effect of diet and LDL receptor genotype on macrophage foam cell formation within the peritoneal cavities of mice. Foam cell formation was associated with significant changes in hundreds of lipid species and unexpected suppression, rather than activation, of inflammatory gene expression. We provide evidence that regulated accumulation of desmosterol underlies many of the homeostatic responses, including activation of LXR target genes, inhibition of SREBP target genes, selective reprogramming of fatty acid metabolism, and suppression of inflammatory-response genes, observed in macrophage foam cells. These observations suggest that macrophage activation in atherosclerotic lesions results from extrinsic, proinflammatory signals generated within the artery wall that suppress homeostatic and anti-inflammatory functions of desmosterol., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Neoadjuvant chemotherapy is used to treat oestrogen receptor-positive breast cancer however chemo-resistance is a major obstacle in this molecular subtype. The ability to predict tumour response would allow chemotherapy administration to be directed towards patients who would most benefit, thus maximising treatment efficacy. We aimed to identify protein biomarkers associated with response to neoadjuvant chemotherapy, in a pilot study using comparative 2-DE MALDI TOF/TOF MS proteomic analysis of breast tumour samples. A total of 3 comparative proteomic experiments were performed, comparing protein expression between chemotherapy-sensitive and chemotherapy-resistant oestrogen receptor-positive invasive ductal carcinoma tissue samples. This identified a list of 132 unique proteins that were significantly differentially expressed (≥ 2 fold) in chemotherapy resistant samples, 57 of which were identified in at least two experiments. Ingenuity® Pathway Analysis was used to map the 57 DEPs onto canonical signalling pathways. We implicate several isoforms of 14-3-3 family proteins (theta/tau, gamma, epsilon, beta/alpha and zeta/delta), which have previously been associated with chemotherapy resistance in breast cancer. Extensive clinical validation is now required to fully assess the role of these proteins as putative markers of chemotherapy response in luminal breast cancer subtypes., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: Chemotherapy resistance is a major obstacle in effective neoadjuvant treatment for estrogen receptor-positive breast cancer. The ability to predict tumour response would allow chemotherapy administration to be directed towards only those patients who would benefit, thus maximising treatment efficiency. We aimed to identify putative protein biomarkers associated with chemotherapy resistance, using fresh tumour samples with antibody microarray analysis and then to perform pilot clinical validation experiments., Materials and Methods: Chemotherapy resistant and chemotherapy sensitive tumour samples were collected from breast cancer patients who had received anthracycline based neoadjuvant therapy consisting of epirubicin with cyclophosphamide followed by docetaxel. A total of 5 comparative proteomics experiments were performed using invasive ductal carcinomas which demonstrated estrogen receptor positivity (luminal subtype). Protein expression was compared between chemotherapy resistant and chemotherapy sensitive tumour samples using the Panorama XPRESS Profiler725 antibody microarray containing 725 antibodies from a wide variety of cell signalling and apoptosis pathways. A pilot series of archival samples was used for clinical validation of putative predictive biomarkers., Results: AbMA analysis revealed 38 differentially expressed proteins which demonstrated at least 1.8 fold difference in expression in chemotherapy resistant tumours and 7 of these proteins (Zyxin, 14-3-3 theta/tau, tBID, Pinin, Bcl-xL, RIP and MyD88) were found in at least 2 experiments. Clinical validation in a pilot series of archival samples revealed 14-3-3 theta/tau and tBID to be significantly associated with chemotherapy resistance., Conclusions: For the first time, antibody microarrays have been used to identify proteins associated with chemotherapy resistance using fresh breast cancer tissue. We propose a potential role for 14-3-3 theta/tau and tBID as predictive biomarkers of neoadjuvant chemotherapy resistance in breast cancer. Further validation in a larger sample series is now required., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A fibulocalcaneus (peroneocalcaneus) internus (PCI) muscle (of MacAlister) was identified and photographed in the left leg of a 78-year-old Caucasian female cadaver. This case study provides the first gross anatomical photo of this anomalous leg muscle and represents the first gross anatomical dissection of this muscle since 1914. The PCI muscle arose from the distal third of the fibula, posterior intermuscular septum of the leg, and flexor hallucis longus muscle. The PCI muscle inserted into the inferior surface of the medial calcaneus distal to the coronoid fossa, a small depression between the anterior tuberosity and the anterior apex of the sustentaculum tali. This insertion point differs from the historical literature, which commonly refers to the muscle inserting into the inferior surface of the sustentaculum tali of the calcaneus or simply distal to the sustentaculum tali into the medial aspect of the calcaneus. The PCI muscle is one of the least common muscular variants associated with the ankle joint, and it has been implicated in posterior ankle pain and impingement, as well as involvement in tarsal tunnel syndrome. This muscle is often confused with the flexor digitorum accessorius longus (FDAL) muscle. Additionally, this study describes ways to differentiate between the PCI and FDAL muscles in the lower leg. Radiologists and clinicians should be aware of this anomalous muscle when considering various diagnoses, interpreting radiographs, and pursuing surgical intervention to relieve posterior ankle symptoms., (Copyright © 2011 Wiley Periodicals, Inc.)

As breast cancer is the most frequent cancer in the elderly with a peak incidence of 1 in 10 by the age of 80, it is important to establish optimum therapy in this group. We conducted a case note-based retrospective study of all elderly primary breast cancer patients aged 80 and above between 1992 and 2002. The type of treatment, complications, disease progression, recurrence, and overall survival were recorded. In all 110 patients aged 80 and above were treated for primary breast cancer, with 32 patients having advanced disease. Of these, 62 patients received primary endocrine treatment. 48 patients underwent surgery with 30 patients undergoing mastectomy. At follow-up, 34 patients suffered disease progression in the primary endocrine treatment group and three patients had local recurrence in the surgical group. The Kaplan-Meier analysis revealed significantly better survival in the surgical treatment group when compared with the primary endocrine treatment group, both in the early disease (n = 41; median survival: 71 months; compared to n = 37; median survival: 42 months; p = 0.0002) and the advanced disease (n = 7; median survival: 48 months; compared to n = 25; median survival: 36 months; p = 0.03). Prompt surgery and adjuvant treatment can decrease relapse and improve survival even in patients older than 80 years.

Background: Neoadjuvant therapy results in a significant increase in breast-conserving surgery. However, traditional imaging methods are unable to accurately predict the extent of viable residual disease leading to uncertainty in surgical planning and some previous studies have shown a disproportionately high incidence of locoregional recurrence. Dynamic contrast enhanced-MRI (DCE-MRI) has been shown to provide a potentially more accurate prediction of residual disease., Results: Patients undergoing neoadjuvant chemotherapy for breast cancer in our unit are staged with the DCE-MRI of the breast performed at 1.5 T before, during and after treatment and the final result was used to plan surgery. Two hundred and four patients with breast cancer were treated with neoadjuvant chemotherapy between 1996 and April 2005. Eighteen of these patients had distant metastases at the time of initial diagnosis and so were excluded from the present study. Following neoadjuvant chemotherapy, 186 patients underwent surgical treatment. Of these, 68 patients had breast-conserving surgery. At a median follow up of 30 months (range: 5.6-72 months) 21 patients in this group developed subsequent recurrence (21/68 - 30%) of whom 9 (9/68 - 13%) had locoregional recurrence, 7 had local recurrence (7/68 - 10%), and 17 (17/68 - 25%) had distant recurrence. Logistic regression analysis revealed only vascular invasion (p=0.006) of the tumour to be significantly associated with overall recurrence. None of the pathological factors (ER, PR status, vascular invasion, lymph node metastases, pathological complete response to neoadjuvant chemotherapy) showed a significant association with locoregional recurrence., Conclusion: Breast-conserving surgery with DCE-MRI planning after neoadjuvant chemotherapy provides an acceptable level of local recurrence without the need for mastectomy.

Aims: This study aimed to examine the feasibility of utilizing dynamic contrast-enhanced MRI (DCE-MRI) of the breast for the planning of surgical intervention following neoadjuvant therapy for locally advanced breast cancer (LABC)., Methods: Following their neoadjuvant therapy, women with LABC were followed-up by DCE-MRI in addition to clinical examination and mammography. If any modality suggested residual disease, surgery was carried out--initially salvage mastectomy and then breast-conserving surgery where appropriate., Results: Seventeen women were recruited: stage III (n=16), stage IV (n=1) mean age 55 (range 34-74). Following neoadjuvant therapy, 10 mastectomies and two local excisions were performed for 10 histologically confirmed residual cancers. Median follow-up for those women not undergoing surgery is 3.24 (IQR 2.8-3.5) years. DCE-MRI proved 100% accurate for the delineation of residual disease and facilitated the planning of the local excisions. Clinical examination and mammography proved inaccurate (PPV 83% and 75% and NPV 55% and 80%, respectively)., Conclusions: DCE-MRI is a potentially accurate method of delineating residual tumour following neoadjuvant therapy for LABC and may be used to plan appropriate operative intervention where required., (Copyright 2001 Harcourt Publishers Limited.)

Purpose: Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. In breast cancer, tumor VEGF has been shown to have a good correlation with relapse-free survival. The aim of this study was to determine the relation of serum VEGF levels to the various indices of breast cancer and known tumor markers carcinoembryonic antigen and CA15.3., Experimental Design: Preoperative serum VEGF levels were determined in 200 women with breast cancer and compared with serum VEGF levels in 88 healthy female controls., Results: The serum VEGF levels of the cancer patients as a group were significantly elevated compared with those of the controls (P < 0.0005). VEGF levels were elevated in patients with invasive cancer of ductal/no specific type, ductal carcinoma in situ, and estrogen receptor (ER)-positive tumors. Patients with lobular carcinoma and ER-negative tumors had serum VEGF levels comparable with those in the controls. VEGF was more sensitive than CA15.3 and carcinoembryonic antigen in detecting breast cancer., Conclusions: Preoperative serum VEGF detects breast cancer with a sensitivity of 62.1%. The relationship to cancer type and ER status may have future therapeutic implications. Additional long-term studies are required to determine the prognostic significance of serum VEGF.

7Alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (ICI 182,780; Faslodex) is a novel steroidal antiestrogen. This partially blind, randomized, multicenter study compared the effects of single doses of long-acting ICI 182,780 with tamoxifen or placebo on estrogen receptor (ERalpha) and progesterone receptor (PgR) content, Ki67 proliferation-associated antigen labeling index (Ki67LI), and the apoptotic index in the primary breast tumors of postmenopausal women. Previously untreated patients (stages T(1)-T(3); ER-positive or -unknown) were randomized and received a single i.m. dose of ICI 182,780 50 mg (n = 39), ICI 182,780 125 mg (n = 38), or ICI 182,780 250 mg (n = 44) or oral tamoxifen 20 mg daily (n = 36) or matching tamoxifen placebo (n = 43) for 14-21 days before tumor resection surgery with curative intent. The ER and PgR H-scores, together with the Ki67LI were determined immunohistochemically in the matched pretreatment biopsy and the posttreatment surgical specimens. The apoptotic index was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling on the same samples. The effects of treatment on each of these parameters were compared using analysis of covariance. ICI 182,780 produced dose-dependent reductions in ER and PgR H-scores and in the Ki67LI. The reductions in ER expression were statistically significant at all doses of ICI 182,780 compared with placebo (ICI 182,780 50 mg, P = 0.026; 125 mg, P = 0.006; 250 mg, P = 0.0001), and for ICI 182,780 250 mg compared with tamoxifen (P = 0.024). For PgR H-score, there were statistically significant reductions after treatment with ICI 182,780 125 mg (P = 0.003) and 250 mg (P = 0.0002) compared with placebo. In contrast, tamoxifen produced a significant increase in the PgR H-score relative to placebo, and consequently, all doses of ICI 182,780 produced PgR values that were significantly lower than those in the tamoxifen-treated group. All doses of ICI 182,780 significantly reduced Ki67LI values compared with placebo (ICI 182,780 50 mg, P = 0.046; 125 mg, P = 0.001; 250 mg, P = 0.0002), but there were no significant differences between any doses of ICI 182,780 and tamoxifen. ICI 182,780 did not alter the apoptotic index when compared with either placebo or tamoxifen. Short-term exposure to ICI 182,780 reduces the ERalpha in breast tumor cells in a dose-dependent manner by down-regulating ER protein concentration. The reductions in tumor PgR content by ICI 182,780 demonstrate that ICI 182,780, unlike tamoxifen, is devoid of estrogen-agonist activity. Reductions in tumor cell proliferative activity (as indicated by Ki67LI) show that ICI 182,780 is likely to have antitumor activity in the clinical setting.

Objective: To compare the sensitivity and specificity of the traditional triple assessment of symptomatic breast lesions with contrast-enhanced dynamic magnetic resonance imaging., Background: Although triple assessment is currently the gold standard for the assessment of symptomatic breast disease, its specificity is such that open biopsies are still required in many cases to be confident of the diagnosis. Contrast-enhanced dynamic magnetic resonance imaging of the breast represents an alternative diagnostic modality., Methods: Patients were recruited from the symptomatic breast clinics. If any of the diagnostic modalities suggested malignancy, the lesion was excised. The remaining patients were followed clinically and radiologically., Results: Two hundred eighty-five patients with a mean age of 43 years (range 21 to 77) were recruited. Malignant lesions were excised in 131 patients and benign lesions in 55 patients. The 99 patients who did not undergo surgery were followed clinically and radiologically for a median of 20 months. The sensitivity of each modality was as follows: clinical examination 84%, mammography 87.6%, fine-needle aspiration cytology 79.1%, triple assessment 99.2%, and magnetic resonance imaging 99.2%. In addition, histologically confirmed multifocal disease was detected in 40 patients on magnetic resonance imaging but in only 9 (22.5%) on mammography. The specificity for the diagnosis of benign disease was as follows: clinical examination 83.1%, ultrasound 88.9%, mammography 86.4%, fine-needle aspiration cytology 97%, triple assessment 59.1%, and magnetic resonance imaging 90.9%., Conclusion: Contrast-enhanced dynamic magnetic resonance imaging of the breast is as sensitive and more specific than the combined traditional triple assessment for the diagnosis of malignant breast lesions.

Background: Inadequately treated multifocal and multicentric disease results in increased local recurrence following breast-conserving surgery. The accurate preoperative diagnosis of multifocal/ centric breast cancer would facilitate the planning of appropriate surgery and prevent reoperation for residual disease. While triple assessment remains the established diagnostic technique, its sensitivity for the diagnosis of multifocal disease remains poor. Dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) of the breast represents an alternative emerging diagnostic modality that has been shown to be highly sensitive for the delineation of primary breast cancer. The aim of this study was to prospectively compare the diagnostic accuracy of DCE-MRI of the breast with conventional triple assessment for the preoperative diagnosis of multifocal/centric breast cancer., Methods: Patients were recruited from the symptomatic breast clinics. All patients underwent standard triple assessment and DCE-MRI. The MRI scans were reported by a single radiologist blinded to the results of the triple assessment. Surgery was then planned accordingly to all available scan results and the specimens examined by a single pathologist. All patients who did not undergo surgery have been followed up for a minimum of 18 months., Results: A total of 334 women were recruited. There were 178 (52%) cancers that were histologically confirmed and multifocal/centric breast cancer was diagnosed provisionally by the preoperative investigations in 68 (38%); multifocal n = 33, multicentric n = 35, of these patients. In this group, subsequent histology confirmed multifocal/centric disease in 50 (73.5%): multifocal n = 15, multicentric n = 35. Unifocal cancer was found in 15 (22%) and benign disease in 3 (4.4%). The resultant sensitivity, specificity, positive, and negative predictive values were 18%, 100%, 100%, and 76% for triple assessment and 100%, 86%, 73%, and 100% for DCE-MRI., Conclusion: DCE-MRI identified a subgroup of breast cancer patients with multifocal/centric disease not evident on standard triple assessment. MRI of the breast should be considered for the preoperative planning of surgery for primary breast cancer.

The cloning of a second estrogen receptor (ER), ER beta, has prompted a reevaluation of the role of ERs in breast cancer. The aim of this study was to determine the expression of both ER isoforms in normal (n = 23) and malignant (n = 60) human breast tissue by reverse transcription-PCR and correlate this information with known prognostic factors including tumor grade and node status. In normal breast tissue, expression of ER beta predominated, with 22% of samples exclusively expressing ER beta; this was not observed in any of the breast tumor samples investigated. Most breast tumors expressed ER alpha, either alone or in combination with ER beta. Interestingly, those tumors that coexpressed ER alpha and ER beta were node positive (P = 0.02; Fisher's exact test) and tended to be of higher grade. Because antiestrogens are agonists when signaling through the AP1 element, overexpression of ER beta in tumors expressing both ER subtypes may explain the failure of antiestrogen therapy in some breast cancer patients. Thus, ER beta may be a useful prognostic factor in patients with breast cancer.

Aims: To design an interactive multimedia program for use by breast-care nurses and evaluate the acceptability of this technology to patients in the clinical setting., Methods: In order to ensure that the clarity of the information was maintained the multimedia program was developed by a multidisciplinary team, including non-medical personnel and patients. A prospective analysis of the subjective impressions of patients with symptomatic breast disorders and breast-care nurses to a multimedia patient information system was then performed using a standard questionnaire and semi-structured interviews., Results: Fifty women were recruited for the study. Thirty-six (72%) considered the multimedia counselling to be superior to the traditional modalities. Forty-nine (98%) graded the system as good or better. No patient regarded the technology as anxiety-provoking or inferior to the traditional leaflet-based approach. Women over 55 years old found the system as acceptable and easy to use as the younger women., Conclusions: The multimedia breast counselling programme was acceptable to patients and was considered superior to the traditional leaflet-based approach by the majority. The inherent advantages of this technology will lead to its increasing utilization in the clinical setting.

Background: Dynamic contrast-enhanced magnetic resonance imaging (MRI) of the breast is highly sensitive for the diagnosis of primary breast malignancy. We investigated the clinical application of dedicated dynamic breast MR for routine screening for local recurrence following breast-conserving therapy., Methods: Patients underwent a single dynamic MR of the breast routinely in the period 1 to 2 years following treatment, or earlier if recurrence was suspected. A biopsy was performed if there was suspicion of recurrence on MR., Results: One hundred and five patients with a median age of 58 years (range 50 to 65 years) were recruited for the study. Sixteen biopsies were performed and nine recurrences were confirmed histologically. Patients not undergoing biopsy have been followed up for a median of 341 days (range 168 to 451 days) following the MR. The sensitivity for clinical examination, mammography, examination combined with mammography, and MRI alone for the detection of recurrent cancer were 89%, 67%, 100%, and 100%, respectively, and the specificity was 76%, 85%, 67%, and 93%., Conclusion: Combined clinical examination and mammography are as sensitive as dedicated dynamic MR of the breast for the detection of locoregional recurrence, but breast MRI is associated with a far greater specificity. Therefore, dedicated dynamic breast MRI should be used when there is clinical or mammographic suspicion of recurrence to confirm or refute its presence.

Objective: To assess dynamic Gd-DTPA-enhanced magnetic resonance (MR) imaging in the diagnosis of primary breast pathology, and to test the hypothesis that analysis of contrast agent kinetics increases specificity., Methods: Forty-seven women underwent breast MR imaging using three-dimensional and dynamic spoiled gradient-recalled sequences. Image interpretation was based on the evaluation of lesion conspicuity, signal intensity, contour and enhancement pattern from the static acquisitions. Assessment of contrast kinetics was based on pixel-by-pixel analysis of the dynamic data. A two-compartment model described by three parameters (amplitude of uptake, exchange rate and washout rate), and a three-compartment model described by two parameters (permeability and exchange rate) were used. Regions of interest were drawn for all lesions found in the dynamic sections. Mean regional pixel values were calculated for each parameter and tested for diagnostic efficacy., Results: Twenty-two malignant and 36 benign lesions were examined. Fibroadenomas accounted for 86% of the benign tumours. Image interpretation had a sensitivity of 0.95 and specificity of 0.86. The fat-suppressed post-contrast images permitted good visualization of the contour and matrix characteristics of fibroadenomas, but all non-fibroadenomatous benign lesions were classified as indeterminate or suspicious. Significant differences were found between benign and malignant lesions in the amplitude of uptake (P = 0.0008) and exchange rate (P < 0.00005) of the two-compartment model, and permeability (P=0.0001) and exchange rate (P < 0.00005) of the three-compartment model. However, image interpretation was superior to the isolated use of quantitative indices (P=0.02). The most discriminating parameters were the exchange rates of both models, with no significant difference between them., Conclusion: Assessment of lesion morphology is essential and probably sufficient for the differentiation of fibroadenomas from malignant tumours. However, specificity of conventional MR imaging may be much lower for other types of primary benign breast pathology. Analysis of Gd-DTPA kinetics improves the specificity obtained using simple enhancement measurements and can be used to produce parametric images that provide information about lesion heterogeneity, permeability and vascularity.

Current practice in this unit for a suspected breast abscess is preliminary ultrasonographic scan, aspiration of any pus, antibiotic therapy and repeat aspiration in the outpatient clinic if necessary. Inflammatory masses are treated with antibiotics alone. A retrospective review of this strategy has been made. Over a 2-year interval 53 patients were admitted to hospital with a suspected breast abscess. Twenty-two abscesses were aspirated, of which 19 resolved and three required subsequent incision and drainage. Eight patients underwent primary incision and drainage, one of whom required a second drainage procedure. In five patients the abscess discharged spontaneously before intervention. The remaining 18 patients were found on ultrasonography to have inflammation without evidence of focal pus which settled with antibiotic therapy in all but two patients. One of these was found to have an inflammatory cancer and the other developed an abscess, which was drained. Aspiration combined with ultrasonographic imaging is an effective alternative to incision and drainage.

Rationale and Objectives: This study was designed to assess the efficacy of dynamic contrast-enhanced magnetic resonance imaging (MRI) of the breast combined with pharmacokinetic analysis of gadolinium (Gd)-DTPA uptake in the diagnosis of local recurrence of early stage breast carcinoma., Methods: Fifty women treated with breast-conserving surgery and radiotherapy underwent breast MRI. Dynamic magnetic resonance data obtained at four preselected slice locations were analyzed to examine Gd-DTPA uptake based on a pharmacokinetic model using three parameters: wash-in rate, wash-out rate, and amplitude of uptake. Synthetic images were produced from the above parameters and their derivatives--maximum uptake and reciprocal of half the time to maximum. For each region of interest (ROI), median parameter values were calculated. The mean pixel signal intensity of each ROI was plotted against time, and an enhancement index was determined., Results: Sixty ROIs were selected: 49 lesions were benign, and 11, malignant. Significant differences between benign and malignant lesions were found for the enhancement index (P < 0.0001), maximum uptake (P < 0.0001), amplitude of uptake (P < 0.0001), wash-in rate (P = 0.03), wash-out rate (P = 0.01), and the reciprocal of half the time to maximum (P = 0.0005). The respective sensitivities and specificities were as follows: for the enhancement index, 1.00 and 0.96; for maximum uptake, 1.00 and 0.96; for amplitude of uptake, 0.91 and 0.94; for wash-in rate 0.82 and 0.47; for wash-out rate 0.91 and 0.59; and for the reciprocal of half the time to maximum, 1.00 and 0.51., Conclusions: Dynamic scanning proved essential for the detection and differential diagnosis of local tumor recurrence. Pharmacokinetic analysis of Gd-DTPA uptake can be used to produce parametric images that retain the spatial resolution of the original images while providing additional information about lesion permeability and vascularity, and helping to avoid the observer variability associated with ROI analysis.

Purpose: To evaluate heavily T2-weighted, dynamic contrast-enhanced and fat-suppressed magnetic resonance imaging (MRI) of the breast in comparison with conventional imaging and fine needle aspiration cytology (FNAC)., Patients and Methods: Fifty patients with surgically/pathologically proven breast disease were examined pre-operatively by MRI. The majority, 45 patients, had invasive carcinoma. T1-weighted spin-echo, T2-weighted fast spin-echo (with chemical-shift-selective fat-suppression in 20 cases), rapid dynamic contrast-enhanced gradient-echo and post-contrast fat-suppressed T1-weighted images were obtained. Signal intensity changes during dynamic scanning were assessed qualitatively and quantitatively. Comparison was made with the results of X-ray mammography, ultrasound and fine needle aspiration cytology., Results: Unenhanced MRI was inadequate for determining the location, extent or nature of most lesions even when fat-suppressed T2-weighted images were obtained. Following contrast injection, there was significantly greater enhancement of invasive carcinomas than normal parenchyma. Invasive carcinomas of ductal and lobular subtypes did not differ significantly in their enhancement profiles. Prominent enhancement of the lesion periphery, which was a feature in 33 out of 50 cases (the majority of which were invasive carcinomas) was not due to central tumour necrosis. In four cases, invasive carcinomas which were clearly visible on early dynamic scans could not be identified on post-contrast fat-suppressed images. Lesions that were more numerous or extensive than had been recognised clinically or mammographically were revealed by MRI in 14 patients, though MRI was no more specific than conventional assessment. Invasion of the chest wall was accurately predicted by MRI in three cases. There was excellent correlation between tumour size shown by MRI and histopathology. FNAC was accurate in predicting the final histological diagnosis except in those cases where samples were unsatisfactory., Conclusions: Contrast-enhanced MRI appears useful in the assessment of suspected malignant breast masses, especially in younger women with predominantly glandular breast tissue. Specificity is no better than FNAC but tumour extent and multifocality are more accurately disclosed than by conventional imaging techniques. Contrast-enhanced chemical-shift-selective fat-suppressed images are sub-optimal in a small proportion of cases (particularly where lesions are located posteriorly) and some benign breast disease may appear misleadingly conspicuous on such images. Morphological features and quantification of lesion enhancement during dynamic scanning presently offer only limited prospects for discrimination between various pathologies. Heavily T2-weighted sequences appear of marginal value.

20 women with suspected recurrent breast cancer who had undergone previous breast-conserving operations were investigated using dynamic contrast-enhanced gradient echo (GRE) and fat suppressed spin echo (SE) magnetic resonance (MR) imaging. Histologically confirmed recurrent tumour was readily recognized on dynamic GRE scans by virtue of rapid, early and avid enhancement. Benign scars enhanced more slowly and reached lower magnitudes of enhancement. Fat suppressed SE images, which were typically acquired 10 min after contrast administration, were sensitive for the detection of tumour recurrence but lacked specificity. Early scanning after contrast administration offers the best prospects for distinguishing tumour recurrence from benign scarring. The criteria used to distinguish these two entities are highly dependent on the scan technique and the time at which images are obtained post-contrast.

The Humberside Breast Screening Service completed 1 year of screening by October 1990; 16,534 women were invited of whom 12,832 (77.6 per cent) attended. A group of 644 women (5.0 per cent) were called for further assessment and of these 134 underwent 135 primary surgical procedures. After assessment 25 were shown before operation to have cancer. One hundred and nine women had suspicious lesions and proceeded to surgical biopsy; 50 lesions proved malignant (benign: malignant biopsy ratio 1.2:1). The 75 malignant lesions represented a prevalence of 5.8 per 1000 of the screened population. Invasive cancer > 1 cm in diameter formed almost half of the malignant lesions. This service has cost 32 pounds per woman screened or 5533 pounds per cancer detected. The results are comparable to those of previous studies and suggest that a mammographic screening service can be successfully provided in a district hospital setting.

Background: Six patients with firm circumferential folds located in the balanic sulcus of the penis were studied., Objective: The purpose of the study was to determine the origin of the lesions., Methods: These patients were examined clinically, with dark-field examination when possible and with a serologic test for syphilis., Results: All patients had reactive serologic tests for syphilis and had enlarged, firm, nontender, inguinal lymph nodes., Conclusion: Although we were unable to prove with certainty that the origin of these folds was syphilitic, all patients had clinical and serologic findings that supported the diagnosis of primary syphilis.

We report a case of drug-induced pemphigus caused by an angiotensin-converting enzyme inhibitor, captopril. The cutaneous reaction remitted after withdrawal of captopril therapy. Unique to this case, however, was the substitution of another angiotensin-converting enzyme inhibitor, enalapril, without exacerbation of the pemphigus. To the best of our knowledge, this is the first reported patient with captopril-induced pemphigus in whom no new lesions developed after subsequent treatment with enalapril. A difference in chemical structure between these two drugs, particularly of a sulfur moiety, may help explain why the drug-induced disease did not recur.

A case of Meckel's diverticulum presenting acutely with spontaneous haemoperitoneum is presented. This complication has not, to our knowledge, been previously reported.

This case report is presented following the specifications of the American Board of Orthodontics. The patient had a true maxillary retrognathism, a mandibular prognathism, and a lower anterior height deficiency. She was treated with a fixed orthopedic appliance, fixed orthodontic appliances, and intermaxillary elastics. [This case was presented to the American Board of Orthodontics in partial fulfillment of the requirement for the certification process conducted by the Board.

A pilot study of 100 consecutive groin wounds after vascular surgery demonstrated lymph leaks in 12 per cent. Lymph leak was significantly associated with wound infection and with prolongation of in-patient stay. A controlled trial was therefore instituted to assess the influence of vacuum drainage in groin wound healing. One hundred and twenty-seven wounds were randomized to drainage (n = 65) or no drainage (n = 62) and the wounds were examined 'blind' by independent observers. No difference in the incidence of lymph leakage or wound infection was noted between the two groups. The routine use of suction drainage for groin wounds in vascular surgery is unnecessary.

Three findings from a study of one hundred black newborn infants examined for pigmented lesions are presented herein: significantly higher incidence than in prior neonatal examinations, a frequent clinical pattern of grouped macules, and an unusual histologic distribution of nevus cell theques. Fifty-one percent of the infants had congenital pigmented lesions. Biopsy specimens of thirty-two lesions were obtained, twenty-six showing histologic changes of lentigo, four melanocytic nevi (nevus-cell nevi), and two ephelides. Three of the four nevi were less than 1.5 cm in diameter and all were of the predominantly junctional type. Clinical appearance was not a consistent guide for classification in the newborn.

Discoid lupus erythematosus and lupus profundus, rare in children, are described in two young girls, one with onset at 3 1/2 years of age, the other at 8 years of age. Unusual nodules of the face that ultimately healed with atrophy and hyperpigmentation showed histologic and immunofluorescent confirmation of lupus erythematosus. These patients, the second and third in the English literature to be treated for childhood lupus profundus with antimalarials, responded successfully to hydroxychloroquine. No systemic involvement was found.

Thirty-one of 290 cats (10.7%) from the area around St Louis, Mo, were infected with Eurytrema procyonis. In some cats, the pancreas was severely affected, with almost complete atrophy and fibrous replacement of the gland. Both bicarbonate and protein secretions were impaired, although clinically evident pancreatic insufficiency was not seen.

In 34 patients suspected of having pancreatic cancer glucose homeostasis and insulin secretion in response to intravenous glucagon (1 mg) were studied prospectively. Twelve patients had pancreatic cancer at laparotomy and the remainder were designated a control group. Responses were also measured in 12 healthy volunteers. There was no significant difference in the rise of blood glucose between the groups after glucagon. The mean plasma insulin concentrations rose rapidly in both groups after glucagon but were significantly lower in the pancreatic cancer group. In patients with obstructive jaundice the plasma insulin response was a better discriminator of pancreatic cancer. Abnormal pancreatic beta-cell function is detectable in patients with pancreatic carcinoma before any change in glucose homeostasis, particularly in patients with obstructive jaundice. The glucagon stimulation test may be useful in the earlier diagnosis of pancreatic carcinoma before the development of clinically overt diabetes mellitus.

Three instances of depigmentation occurring in children with congenital large nevocytic nevi are reported. Serologic studies for tumour-associated antigens to melanoma were performed by indirect immunofluorescence and complement fixation on these patients and others with benign melanocytic disorders. Positive reactivity in several children was observed. The small numbers studied and lack of uniformity of other testing methods leave open the question of relevance of such reactivity to malignant conversion or protection in congenital nevi.

A complication of massive upper gastrointestinal bleeding is presented as a case report of a patient who developed a spontaneous perforation of the small intestine as a result of massive bleeding from a duodenal ulcer.