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Purpose: Sexual minority women (SMW) may have a different distribution of breast cancer risk factors than their heterosexual peers. Epidemiologic studies of breast cancer in SMW have been limited, and many use only proxy variables to identify SMW in data sets, introducing selection bias. We utilized National Health Interview Survey (NHIS) data to compare breast cancer risk factors, screening, and prevalence between SMW and non-SMW. Methods: We identified female respondents to the NHIS from 2013 to 2017, selected women ≥40 years old and stratified by sexual orientation. We compared demographics and health maintenance variables and prevalence of breast cancer diagnosis between groups and performed a multivariable analysis of breast cancer risk. Results: Of 58,378 women ≥40 years old, 1162 (2.0%) were identified as SMW. SMW were younger and more likely to use tobacco and alcohol, be younger at menarche, and be nulliparous. SMW also reported less preventive care, and despite reporting equivalent rates of mammography, were more likely to obtain mammograms due to an identifiable problem and not simply for screening purposes. Prevalence of breast cancer was similar between SMW and non-SMW (4.7% vs. 5.0%, p = 0.67), and SMW status was not associated with breast cancer diagnosis on univariate and multivariable logistic regression (p = 0.14 and p = 0.07, respectively). Conclusion: Despite finding no difference in breast cancer prevalence between SMW and non-SMW, there was evidence for differences in the utilization of breast care. Further studies of breast cancer incidence, characteristics (including subtype and stage), treatment, and survival for SMW are needed.

Background: Breast cancer is traditionally not considered as a highly immunogenic disease. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with reported high genomic instability and high mutation rate, indicating the possible presence of neoantigens. Cryoablation, the destruction of cells by ultra-low temperatures, can release these neoantigens and induce a tumor specific immune response. We hypothesized these neoantigens might be sufficient to trigger a robust immune response to prevent and/or reduce spread and relapse of TNBC. In this pilot study we cryoablated orthotopical 4T1 tumors in immune competent Balb/c mice and compared the results to surgery to evaluate 1) possible induction of immune responses and 2) effects on metastases formation. Methods: We used 4T1 mammary carcinoma cells to initiate tumor growth in the mammary fatpad. Tumors were treated by cryoablation, cryoablation followed by surgery (cryo-surgery), or surgery alone. Tumor growth was followed and allowed to reach 3-4mm in largest dimension. Animals were euthanized 7 days post-treatment and tissues were collected to assess cytokine levels and presence of dissociated 4T1 cells. Single-cell suspensions of tumor, tumor-draining lymph node [TDLN], and spleen were tested for secretion of mouse Th1/Th2 cytokines using a bead array and measured by flow cytometery. Possible metastatic spread was assessed by a clonogenic assay using cells from venous blood, lung, and brain. Cell suspensions were seeded in growth medium supplemented with the selection agent 6-thioguanine, allowing only resistant 4T1 cells to form colonies. Results: Cryoablation transformed tumors into a gelatinous mass surrounded by a fibrotic capsule, as typically seen in the clinic. Frozen sections of tumors revealed a necrotic core and infiltrating lymphocytes in the microenvironment. These animals displayed robust increases of Th1 and Th2 cytokines in both spleen and TDLN compared to animals with cryo-surgery treatment. TDLN of animals with surgically excised tumors secreted only IL-2. Circulating tumor cells were found in animals prior to treatment, while no 4T1 colonies formed from cell suspensions of lung and brain tissue [N=8]. At end-point, the surgery alone group had more 4T1 foci formed from lung and brain [mean foci /animal = 6.25 and 0.75, respectively; N=6] than the other two groups. Two animals in this group progressed and were euthanized early due to numerous lung metastases. The cryoablated group had the lowest number of foci formed in the lung and brain [2.25 and 0 respectively; N=8], and all animals were healthy at the predetermined end-point. Mean foci formation in the cryo-surgery group [N=7] was in-between the two other groups and one animal was euthanized early due to metastatic burden 5 days after surgery. Conclusion: Cryoablation of TNBC can induce stimulatory immune responses in vivo. These immune responses might explain why animals treated with cryoablation, though having circulating tumor cells at the time of treatment, exhibited fewer micro metastatic growths compared to surgery alone and the cryo-surgery combination. On-going experiments aim to identify long-term effects of cryoablation on the formation of metastatic foci and growth. Citation Format: Klein JD, Aukers Z, Kennedy J, Ciocca RM, Sabol JL, Carp NZ, Wallon UM. Cryoablation of murine mammary tumors induce robust immune response [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-11.

Background: Cryoablation, the destruction of cells by ultra-low temperatures, has been used to treat benign breast disease and two clinical trials (ACOSOG Z1072 and FROST) have been conducted to determine its utility in invasive breast cancers. The focus of the trials has been the rate of complete tumor ablation with no assessment of immunological responses. We hypothesize that neoantigens released during cryoablation might be sufficient to trigger a robust immune response to prevent and/or reduce spread and relapse of breast cancers. In this pilot study we 1) evaluated biopsy material, cryoablated specimens and axillary lymph nodes from patients with cancers smaller than 2cm enrolled in the ACOSOG Z1072 trial at Lankenau Medical Center [N=18] and 2) assessed immune responses and effects on metastases formation in the classical mouse mammary tumor model 4T1 in immune competent Balb/c mice. In both settings responses were compared to patients/mice treated with surgical resection alone. Methods: After obtaining IRB approval for retrospective analyses of specimens from the ACOSOG Z1072 trial, immunohistochemical staining of surgical specimens was performed. Sections were stained for CD4, CD8, CD20, CD21, and CD1c. In the IACUC approved animal experiments, 4T1 cells were injected orthotopically in the mammary fatpad to initiate tumor growth. Small tumors were treated by cryoablation or surgery alone. Animals were euthanized 7 days post-treatment and tissues were collected to assess cytokine levels and presence of dissociated 4T1 cells. Single-cell suspensions of tumor, tumor-draining lymph node [TDLN], and spleen were tested for secretion of mouse Th1/Th2 cytokines using a bead array and measured by flow cytometry. Possible metastatic spread was assessed by a clonogenic assay using cells from venous blood, lung and brain. Cell suspensions were seeded in growth medium with the selection agent 6-thioguanine, allowing only resistant 4T1 cells to form colonies. Results: Cryoablation transformed tumors in both patients and mice into a gelatinous mass surrounded by a fibrotic capsule. Sections of tumors from both humans and mice displayed a necrotic core and infiltrating lymphocytes in the microenvironment. The cryoablated human tumors had slightly higher presence of lymphocytes positive for CD8+ compared to CD4+. The inverse relation was observed in non-cryoblated specimens. No significant difference was observed for CD20+ lymphocytes. Tumor-draining lymph nodes from cryoablated patients had an elevated presence of CD20+ B cells compared to patients treated by surgery alone. Follicular dendritic cells (CD21+) were also present at higher numbers in TDLN from cryoablated patients. Animals treated with cryoablation displayed robust increases of Th1 and Th2 cytokines in both spleen and TDLN compared to animals with surgery treatment. In the animals, circulating tumor cells were found prior to treatment, while no 4T1 colonies formed from cell suspensions of lung and brain tissue [N=8]. At end-point, the surgery group had more 4T1 foci formed from lung and brain [mean foci /animal = 6.25 and 0.75, respectively; N=6] than the cryo group that had 2.25 and 0 foci in lung and brain, respectively [N=8]. Conclusion: Cryoablation of breast cancer lesions can induce stimulatory immune responses in vivo. These immune responses might explain why animals treated with cryoablation, though having circulating tumor cells at the time of treatment, exhibited fewer micro metastatic growths compared to surgery alone. The presence of elevated numbers of CD20+ in TDLN has been associated with improved disease-free survival. All local patients in the clinical trial are currently disease-free (5 to 9-year F/U) which is higher than expected recurrence rate at ~15% at 9 years post treatment. Citation Format: Allison A Campoverde, Jonah D Klein, Zachary Aukers, John Kennedy, Vlasta Zemba-Palko, Vincenzo Ciocca, Robin M Ciocca, Jennifer L Sabol, Ned Z Carp, Margaretha Wallon. Immune responses triggered by cryoablation of breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-22.

The Italian National Centre for Oncological Hadrontherapy (CNAO) has been treating patients since 2011 with carbon-ion beams using the active-scanning modality. In such irradiation modality, the beam spot, which scans the treatment area, is characterised by very high particle-fluence rates (more than 105 s-1 mm-2). Moreover, the Bragg-peak is only ~1 mm-FWHM. Commercial tissue-equivalent proportional counters (TEPC), like the Far West Technologies LET-½, are large, hence they have limited capability to measure at high counting fluence rates. In this study we have used two home-made detectors, a mini-TEPC 0.81 mm2 in sensitive area and a silicon telescope 0.125 mm2 in sensitive area, to perform microdosimetric measurements in the therapeutic carbon-ion beam of CNAO. A monoenergetic carbon-ion beam of 189.5 ± 0.3 MeV/u scanning a 3 × 3 cm2 area has been used. Spectral differences are visible in the low y-value region, but the mean microdosimetric values, measured with the two detectors, result to be pretty consistent, as well as the microdosimetric spectra in the high y-value region.

BACKGROUND – Tissue inhibitor of metalloproteinase-4 (TIMP-4) is a secreted multi-functional protein associated with poor survival prognosis among early-stage triple-negative breast cancers (TNBC). TNBC represent a highly aggressive form of this disease with an unmet need for effective predictive markers and targeted therapy. Extracellular TIMP-4 binds to the membrane bound tetraspanin CD63 and induces the activation of the tumor promoting PI3K/AKT/mTOR pathway. Here we report that TIMP-4 induced aggressive tumor growth and metastasis can be adverted by directly targeting TIMP-4 using a newly developed monoclonal antibody (mAb) to sequester TIMP-4 and the varied responses to common chemotherapy (CTX) regimen. METHODS – The role of elevated TIMP-4 in TNBC cell behavior was tested in cell culture and animal experiments using the human breast cancer line MDA-MB-468. Cells with or without TIMP-4 added to the medium were used to determine the effects on growth, clonogenic survival and response to chemotherapeutic agents such as adriamycin, Taxol, and the new TIMP-4 mAb. The same cell-line was used to induce tumor growth in nude mice with or without TIMP-4 containing slow-release pellets implanted into the mammary fatpad (mfp). Tumor growth and response to therapy was followed over a six-week period. Lungs, liver, spleen and mfp were collected and analyzed for presence of human cells using a specific anti-human MHC I mAb. Prospectively collected patient samples, in accordance with the IRB approved protocol, were tested for circulating levels of TIMP-4 using a commercially available ELISA assay in samples collected prior to chemotherapy and at each treatment cycle. The medical oncology staff recommended therapy without knowledge of TIMP-4 status. RESULTS – Augmentation of TIMP-4 levels in cell culture medium or the mfp of mice resulted in similar tumor phenotype as in the clinic; fast growing tumors with accelerated disease progression. Elevated TIMP-4 levels in the tumor environment resulted in a 1.5-fold increased growth rate with liver and/or lung metastasis in 25% of animals (N=16). No metastases were found in animals with normal TIMP-4 levels. Treating cell cultures or tumor-bearing mice (i.p. injections) with our TIMP-4 mAb resulted in decelerated growth rate and no detectable metastatic disease in the animals. Results from patient samples demonstrated that circulating TIMP-4 levels in breast cancer patients remain elevated after definitive surgery, indicating that TIMP-4 might continuously stimulate any remaining disseminated tumor cells. Adriamycin containing regiments was the only CTX to suppress the TIMP-4 levels independent of primary tumor size and nodal status. CONCLUSIONS – Based on these clinical and experimental data we suggest that TIMP-4 may represent a prognostic and predictive marker, and a therapeutic target for TNBC patients at highest risk. The presence of TIMP-4 identifies a patient population likely to recur quickly due to continuous activation of the PI3K/AKT/mTOR pathway. Though adriamycin therapy can reduce the TIMP-4 levels, the toxicity of this agent suggests that targeted therapy of the PI3K/AKT pathway and/or a biological therapeutic approach directed against TIMP-4 may be of benefit in this subset of pts and should be further explored. Citation Format: U Margaretha Wallon, Jennifer L Sabol, Vlasta Zemba-Palko, James S DuHadaway, Erica Sutanto-Ward, Zonera A Ali, Paul B Gilman, Robin M Ciocca, Ned Z Carp, George C Prendergast. TIMP-4 is a prognostic and predictive marker in triple-negative breast cancers [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-54.

Usefulness of Urine as a Sample for Detection of Brucella Spp in Male Canines Urine was used as a sample and Sensitivity (S), Specificity (Sp) and the positive Likelihood Ratio (LR+) of molecular and serological methods, combined with epidemiology and the clinical symptoms for detection of Brucella spp., were compared in blood and urine samples from 241 male canines. The rapid slide agglutination test together with 2- mercaptoethanol (2-ME RSAT) were used as a screening test, followed by confirmation using an indirect immunoenzymatic assay (iELISA) and bacteriological culture. Results were as follows: Test a) PCR (Polymerase Chain Reaction) of blood compared to blood culture: S 80%, Sp 92%, LR+ 10.32% (CI 5.27-19.20) test b) iELISA compared to blood culture: S 100%, Sp 94%, LR+: 16.57%) (CI 9.97-27.53), test c) PCR of urine compared to urine culture: S 100%, Sp 93% (CI 8.36-21.56), LR+: 13.64 test d) iELISA compared to urine culture: S 100%, Sp 93%, RV+: 14.5 (CI 9.03-23.26). We conclude that molecular and serological tests in conjunction with epidemiology are both useful for diagnosis and that both blood and urine samples should be assayed together.

BACKGROUND: Triple-negative breast cancers (TNBC) represent a highly aggressive form of this disease with few treatment options available. Currently, even the smallest node negative cancers are considered by many to warrant treatment with chemotherapy (CTX). While many recur early (within 2–3 years), there is a subset of long-term survivors illustrating the heterogeneity within this group. Here we report our ongoing effort to establish tissue inhibitor of metalloproteinase-4 (TIMP-4) as a prognostic marker in all early breast cancers a. While the canonical function of TIMPs is to inhibit tissue degradation, numerous reports have established that TIMPs exert tumor promoting activity. In our prospective study, we evaluated TIMP-4 as prognostic marker for TNBC and its role in disease progression. METHODS: Specimens from our retrospective and prospective cohorts were assessed by immunohistochemical staining using standard techniques and a monoclonal antibody for TIMP-4b in accordance with the IRB approved protocol. Staining intensity was documented on a scale of 0–3. No data was released to the treating physicians at the time of collection. Outcome data from a total of 240 pts was obtained through tumor registry and clinician practices. Staining intensity was then correlated with outcome to calculate sensitivity and specificity of the marker. To determine the role of TIMP-4 in TNBC cell behavior we have performed microarray analyses. The effects of TIMP-4-induced signaling were tested using invasion and clonogenic survival assays under normal growth conditions and after exposure to gamma radiation. RESULTS: Elevated TIMP-4 expression identified a high risk of relapse and short survival time with 75% sensitivity and 80% specificity. No discernable differences were noted between retrospective and prospective cohorts. Array analyses revealed activation of the PI3K/AKT pathway in the presence of TIMP-4. Furthermore, elevated TIMP-4 increased the invasive behavior of breast cancer cells in Matrigel™-coated invasion chambers and reduced sensitivity to gamma irradiation. These effects were reversible by addition of either a PI3K inhibitor or an anti-TIMP-4 antibody, suggesting their use as potential therapeutic strategies. CONCLUSIONS: On the basis of these clinical data we suggest that TIMP-4 may offer a simple prognostic marker for TNBC patients at highest risk. The presence of TIMP-4 identifies a patient population likely to recur quickly despite standard CTX treatment. Our research suggests that targeted therapy of the PI3K/AKT pathway and/or a biological therapeutic approach directed against TIMP-4 may be of benefit in this subset of pts and should be explored. Therefore, TIMP-4 testing of TNBC patients could aid in the selection of a treatment regimen to improve survival outcome. a Liss, M et.al. Am. J. Pathol. 2009 b Donover, P et.al. J. Cell. Biochem. 2010 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-21.

The benefit of breast MRI for newly diagnosed breast cancer patients is uncertain. This study characterizes those receiving MRI versus those who did not, and reports on their short-term surgical outcomes, including time to operation, margin status, and mastectomy rate.All patients seen in a multidisciplinary breast cancer clinic from July 2004 to December 2006 were retrospectively reviewed. Patients were evaluated by a radiologist, a pathologist, and surgical, radiation, and medical oncologists.Among 577 patients, 130 had pretreatment MRIs. MRI use increased from 2004 (referent, 13%) versus 2005 (24%, p=0.014) and 2006 (27%, p=0.002). Patients having MRIs were younger (52.5 versus 59.0 years, p0.001), but its use was not associated with preoperative chemotherapy, family history of breast or ovarian cancer, presentation, or tumor features. MRI was associated with a 22.4-day delay in pretreatment evaluation (p=0.011). Breast conserving therapy (BCT) was attempted in 320 of 419 patients with complete surgical data. The odds ratio for mastectomy, controlling for T size and stage, was 1.80 after MRI versus no MRI (p=0.024). Patients having MRIs did not have fewer positive margins at lumpectomy (21.6% MRI versus 13.8% no MRI, p=0.20), or conversions from BCT to mastectomy (9.8% MRI versus 5.9% no MRI, p=0.35).Breast MRI use was not confined to any particular patient group. MRI use was not associated with improved margin status or BCT attempts, but was associated with a treatment delay and increased mastectomy rate. Without evidence of improved oncologic outcomes as a result, our study does not support the routine use of MRI to select patients or facilitate the performance of BCT.

BACKGROUND. Sentinel lymph node (SN) biopsy is standard for breast cancer staging, but SN dye gradients and their significance have never been characterized. If predictive of SN metastasis location, their use for focused pathology examination might improve intraoperative imprint cytology sensitivity. METHODS. This prospective trial enrolled clinically lymph node-negative patients with invasive breast cancer not undergoing neoadjuvant chemotherapy. Surgeons marked SN gradients at their bluest end. Nodal halves were examined separately by imprint cytology, and the marked SN half was correlated to metastasis location. Demographic, pathologic, and prognostic features were recorded. RESULTS. Mean patient age and tumor size for the 102 patients was 59.6 years and 2.2 cm, respectively. Of 169 SNs, 159 (94.1%) had dye gradients, which varied by tumor quadrant, but not by histology, diagnosis method, grade, or stage. Among 41 marked SNs with metastases, 92.7% were present in the halves marked by the surgeon. Fourteen were confined to 1 nodal half, with 11 on the marked side and 3 on the unmarked side (P = .029). Metastases were smaller when confined to 1 versus both SN halves (0.14 vs 0.75 cm; P = .005), and smaller (0.87 vs 0.13 cm; P < .0001) when missed intraoperatively. CONCLUSIONS. Dye gradients occur in most SNs and predict metastasis location. The smallest metastases are hardest to detect intraoperatively and are usually confined to the marked SN half. This suggests that marking an SN's bluest half warrants further study to explore whether its correlation to metastasis location may be exploited to focus pathologic examination and decrease the reoperative axillary dissection rate. Cancer 2008. © 2008 American Cancer Society.

Lobular carcinoma in situ (LCIS) is known to be a risk factor for the development of invasive breast cancer. Debate continues as to whether LCIS is also a precursor lesion. We hypothesized that, if LCIS were a precursor, its presence in the lumpectomy specimen, particularly at the margin, could increase local recurrence (LR) after breast-conserving therapy (BCT).2894 patients treated with BCT for ductal carcinoma in situ (DCIS), stage I or II breast cancer between 1/80 and 5/07 were identified. Patients with DCIS or invasive cancer at the margins or those receiving neoadjuvant therapy were excluded. Group A had 290 patients with LCIS in the lumpectomy; 84 had LCIS at the final margin. Group B included 2604 patients with no evidence of LCIS.Median patient age in group A and B was 57 and 58 years, respectively (P = 0.05); 12% and 13%, respectively, of patients in group A and B had margins2 mm (P = NS). The histologic distribution of tumor types in group A was lobular in 47.2%, ductal in 34.5%, DCIS in 11.4%, and other invasive histologies in 6.9%, compared with 4.1%, 76.3%,13.6%, and 6.0% for group B, respectively (P0.0001). There was no significant difference between the groups in tumor-node-metastasis (TNM) stage. The crude rate of LR was 4.5% in group A and 3.8% in group B (P = NS). Five- and 10-year actuarial LR rates for LCIS at the margin were 6% and 6%, 1% and 15% for LCIS present but not at the margin, and 2% and 6% for no LCIS (P = NS), for group A and B, respectively. In multivariate analysis, menopausal status and adjuvant therapy use were significant predictors of LR. LCIS, either in the specimen or at the margin, was not significantly associated with LR.Presence of LCIS, even at the margin, in BCT specimens does not have an impact on LR. Re-excision is not indicated if LCIS is present or close to margin surfaces. These findings do not support consideration of LCIS as a precursor to the development of invasive lesions.

Purpose: The quality assurance (QA) procedure has to check the most relevant beam parameters to ensure the delivery of the correct dose to patients. Film dosimetry, which is commonly used for scanned ion beam QA, does not provide immediate results. The purpose of this work is to answer whether, for scanned ion beam therapy, film dosimetry can be replaced with the 2D MatriXX detector as a real-time tool. Methods: MatriXX, equipped with 32×32 parallel plate ion-chambers, is a commercial device intended for pre-treatment verification of conventional radiation therapy.The MatriXX, placed at the isocenter, and GAFCHROMIC films, positioned on the MatriXX entrance, were exposed to 131.44 MeV proton and 221.45 MeV/u Carbon-ion beams.The OmniPro-I’mRT software, applied for the data taking of MatriXX, gives the possibility of acquiring consecutive snapshots. Using the NI LabVIEW, the data from snapshots were logged as text files for further analysis. Radiochromic films were scanned with EPSON scanner and analyzed using software programs developed in-house for comparative purposes. Results: The field dose uniformity, flatness, beam position and beam width were investigated. The field flatness for the region covering 6×6 cm2 square field was found to be better than 2%. The relative standard deviations, expected to be constant over 2×2, 4×4 and 6×6 pixels from MatriXX measurement gives a uniformity of 1.5% in good agreement with the film results.The beam center position is determined with a resolution better than 200 µm for Carbon and less than 100 µm for proton beam.The FWHM determination for a beam wider than 10 mm is satisfactory, whilst for smaller beams the determination is uncertain. Conclusion: Precise beam position and fast 2D dose distribution can be determined in real-time using MatriXX detector. The results show that MatriXX is quick and accurate enough to be used in charged-particle therapy QA.

Objective: To determine if mexiletine is effective therapy for myotonia in patients with Non-Dystrophic Myotonia (NDM). Background NDM results from rare mutations of muscle sodium and chloride channels. Patients experience delayed muscle relaxation following contraction and functionally limiting stiffness and pain. Mexiletine, a class 1B antiarrhythmic medication with a high affinity for muscle sodium channels, may reduce myotonia in NDM. Design/Methods: We conducted a randomized, double-blind, placebo controlled, cross over trial of mexiletine 200 mg three times daily in 59 patients with NDM at 7 centers in 4 countries. Each treatment period was 4 weeks, separated by a 1 week wash-out. The primary outcome was patient reported stiffness on an interactive voice response diary (IVR). Secondary endpoints included changes in pain, weakness, and tiredness on the IVR, SF-36, INQoL, clinical myotonia assessment, electrophysiological short and long exercise testing, quantitative grip myotonia, and needle EMG. Results: Last year we reported mexiletine provides major benefit for all symptoms of myotonia on the IVR and SF-36 quality of life measures, without study-related serious adverse events. Here we report mexiletine improves symptoms and signs of myotonia: (1) For almost all subdomains on the INQoL, most notably in muscle locking and perceived treatment effects; (2) Reduces time to open the eyes (-0.75 seconds, p=0.0008) and fist (-1.32 seconds, p Conclusions: Mexiletine at a dose of 200 mg three times daily is effective therapy for symptoms and signs of myotonia in patients with NDM. Supported by: FDA Orphan Products Division grant# RO1 FD003454 and the NIH National Institute of Neurological Disorders and Stroke grant# U54 NS059065-05S1. Disclosure: Dr. Statland has nothing to disclose. Dr. Salajegheh has nothing to disclose. Dr. Bundy has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Raja Rayan has nothing to disclose. Dr. Trivedi has nothing to disclose. Dr. Sansone has nothing to disclose. Dr. Venance has received personal compensation for activities with Genzyme Corporation. Dr. Ciafaloni has nothing to disclose. Dr. Matthews has nothing to disclose. Dr. Meola has nothing to disclose. Dr. Zanolini has nothing to disclose. Dr. Ciocca has nothing to disclose. Dr. Herbelin has nothing to disclose. Dr. Griggs has nothing to disclose. Dr. Barohn has received personal compensation for activities with Talecris Biotherapeutics, Genzyme Corporation and Speakers Bureau. Dr. Barohn has received research support from Alexion Pharmaceuticals. Dr. Hanna has nothing to disclose. The Consortium for Clinical Investigation of Neurologic Channelopathies has nothing to disclose.

In the past 20 years, the approach to biliary lithiasis has changed tremendously as a result of advances in endoscopic and laparoscopic techniques. The two most important open surgical techniques involve extraction of the stones from the common bile duct combined with choledochoenterostomy and papillotomy followed by transduodenal papillosphinteroplasty. Ideally, the choledochotomy is followed by the insertion of a T-tube in the common bile duct. The transcystic approach has never been considered. The first endoscopic papillotomy was performed in 1973. Subsequently, it became the most widely used method for removal of common bile duct stones. In this report we explore the possibility of performing a laparoscopic transduodenal papillosphincteroplasty, following the strict rules commonly used in surgery. After cholecystectomy, a Fogarty catheter, is introduced through the cystic duct. This is followed by a minimal duodenotomy, then incision of the papillar sphincter. In this surgical proposal, we do not intend to substitute technique, but this method should be considered the ultimate solution in the laparoscopic approach to cholecystic choledocholithiasis.

locations of cancellous bones than in those of cortical bones. This explains why the ratio of cortical bone mineral content to cancellous bone mineral content may indicate that estrogen deficiency has taken place in the past. In this study, we sought to establish normal Im values in Mexican women. For this purpose, 465 healthy Mexican women with no conditions known to affect bone metabolism were studied by bone densitometry (DXA) in multiple centers using Lunar DPX equipment. In all cases, bone mineral density (BMD) assessment of the spine and femoral neck was carried out. The Im was calculated using Lunar reference values from the normal Hispanic population with the following formula: Im 5 Z value of Lmin 2 Z value from femoral neck, where Lmin is the Z value of the vertebrae with the lowest value. Three groups of patients were investigated: (1) 148 premenopausal women; (2) 233 postmenopausal women without hormone replacement therapy (HRT); and (3) 84 postmenopausal women with HRT from the first year of menopause. Significant differences were found between the average of Im in postmenopausal women (21.137) vs. premonopausal women (20.286) (p , 0.0001) and vs. postmenopausal women with HRT (20.213) (p , 0.0001). With the increase in the number of years since onset of menopause, Im of postmenopausal women has been shown to decrease linearly. Calculation of Im in other locations, such as the trochanter or the femoral neck, is not a good indicator of postmenopausal bone loss. Onset and degree of postmenopausal bone loss may be determined by the difference between Z of Lmin and the femoral neck during the first densitometric assessment. In healthy perimenopausal women, an Im of ,20.3 indicates onset of menopausal bone loss. The degree of bone loss caused by estrogen deficit in the past may be determined for each woman by comparing her index to the average Im of postmenopausal women up to 65 years of age. This new index provides a dynamic evaluation of BMD and is an aid in the differential diagnosis. It also represents an advancement in the treatment of osteoporosis and estrogen deficiency.

Evaluation of Hypothalamo-Pituitary-Gonadal (HPG) Function in Prepubertal Males (PPM) with Hepatic Insufficiency (HI) before H Transplantation (Tx)

The propyne, or me thy1ace ti1ene, molecules (CH3CCH) have received scarce attention in the development of optically pumped infrared lasers.

One thousand five hundred and seventeen HBsAg carriers from different cities of Argentina were studied for the presence of anti-Delta antibody (anti-HDV) in their sera. One thousand one hundred and sixty-eight were volunteer blood donors and 349 were patients with liver disease. Different liver diseases were diagnosed by clinical, biochemical, and histological parameters. Among blood donors, 16 (1.4%) were positive for the antibody and none was Delta-antigen positive. In 130 patients with acute hepatitis, one (0.77%) was positive for anti-HDV, as well as three (2.22%) out of 135 patients with chronic active hepatitis (CAH), and three (5.77%) out of 52 patients with cirrhosis (C). No anti-HDV positive was found among seven fulminant hepatitis (FH) cases. The presence of HBeAg and anti-HBe was studied in anti-HDV positive sera; eleven (69%) volunteer blood donors were anti-HBe positive, and five (31%) were HBeAg positive. HBeAg was positive in the three CAH cases, and in one out of three C Cases with anti-HDV positive. Hepatitis Delta antigen was also positive in the hepatocytic nuclei in the three patients with C and two of the three CAH cases. The present results show that Delta infection is rare among blood donors in Argentina. A small variation without statistical significance could be found within different geographical areas. Among patients with HBsAg related liver disease, the presence of HDV markers was also low.

The optogalvanic effect in the positive column of a neon discharge has been investigated both experimentally and theoretically. A mechanically chopped dye laser was tuned to several 1si–2pj neon transitions (Paschen notation). Optogalvanic spectra and their dependence on the current (1–5 mA) for the 594.5-nm optogalvanic resonance were analyzed. Furthermore, fluorescence and laser-induced fluorescence from the discharge have been examined. A general model based on the steady-state solution of rate equations has been developed in order to interpret the optogalvanic and fluorescence measurements. Good agreement between optogalvanic measurements and theoretical predictions was obtained, but there is a discrepancy between the theoretical prediction and the observed laser-induced fluorescence, which exposes the limitations of the model.