bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Change in Telomere Length and the Chronic Stress Response in a Randomized Pilot Biobehavioral Clinical Study: Implications for Cancer Prevention
Authors: Biegler Kelly A. , Anderson Amanda K. L. , Wenzel Lari B. , Osann Kathryn , Nelson Edward L.
Published: July 2012

Shortened telomere length is associated with increased cancer incidence and mortality. Populations experiencing chronic stress have accelerated telomere shortening. In this exploratory study, we examined associations between longitudinal changes in patient reported outcomes (PRO) of psychologic distress and peripheral blood mononuclear cell (PBMC) telomere length to test the hypothesis that modulation of the chronic stress response would also modulate telomere dynamics. Archived PBMC specimens (N = 22) were analyzed from a completed and reported randomized, longitudinal trial that showed a psychosocial telephone counseling intervention improved quality of life (QOL) and modulated stress-associated biomarkers in cervical cancer survivors. PROs and biospecimens were collected at baseline and 4 months postenrollment. Telomere length of archived PBMCs was evaluated using the flow-FISH assay. Longitudinal changes in psychologic distress, measured by the Brief Symptom Inventory-18, were significantly associated with increased telomere length within the CD14+ (monocyte) population (r = −0.46, P = 0.043); a similar trend was observed for the CD14− population. Longitudinal changes in telomere length of the CD14− subset, primarily T lymphocytes, were associated with longitudinal increases in the naive T-cell population (r = 0.49, P = 0.052). Alterations in the chronic stress response were associated with modulation of telomere length in PBMCs, with evidence for mobilization of “younger” cells from progenitor populations. These data provide preliminary support for the (i) capacity to modulate the chronic stress response and the associated accelerated telomere shortening, (ii) inclusion of telomere length in the biobehavioral paradigm, and (iii) potential link between the chronic stress response and biologic mechanisms responsible for genomic integrity and carcinogenesis. Cancer Prev Res; 5(10); 1173–82. ©2012 AACR.
An EMILIN1-Negative Microenvironment Promotes Tumor Cell Proliferation and Lymph Node Invasion
Authors: Danussi Carla , Petrucco Alessandra , Wassermann Bruna , Modica Teresa Maria Elisa , Pivetta Eliana , Belluz Lisa Del Bel , Colombatti Alfonso , Spessotto Paola
Published: July 2012

The evidence that EMILIN1 (Elastic Microfibril Interface Located proteIN) deficiency in Emilin1−/− mice caused dermal and epidermal hyperproliferation and an abnormal lymphatic phenotype prompted us to hypothesize the involvement of this extracellular matrix component in tumor development and in lymphatic metastasis. Using the 12-dimethylbenz(α)anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) two-stage model of skin carcinogenesis, we found that Emilin1−/− mice presented an accelerated formation, a higher incidence, and the development of a larger number of tumors compared with their wild-type littermates. EMILIN1-negative tumors showed more Ki67-positive proliferating cells and higher levels of pErk1/2. In these tumors, PTEN expression was lower. Emilin1−/− mice displayed enhanced lymphangiogenesis both in the tumor and in the sentinel lymph nodes. Accordingly, tumor growth and lymph node metastasis of transplanted syngenic tumors were also increased in Emilin1−/− mice. In vitro transmigration assays through lymphatic endothelial cells showed that EMILIN1 deficiency greatly facilitated tumor cell trafficking. Overall, these data established that EMILIN1 exerts a protective role in tumor growth, in tumor lymphatic vessel formation, as well as in metastatic spread to lymph nodes and reinforced the importance of its presence in the microenvironment to determine the tumor phenotype. Cancer Prev Res; 5(9); 1131–43. ©2012 AACR.
The Advantages of Oral Cytopathology in the Early Diagnosis of HIV/AIDS: Three Case Reports
Authors: Dias Eliane Pedra , Sayed Picciani Bruna Lavinas , de Carla Batista Santos Vanessa , Oliveira Silva-Junior Geraldo , Heffer Cantisano Marília , Silva-Junior Arley
Published: July 2012

Oral lesions are common in human immunodeficiency virus (HIV)-infected patients, which may indicate impairment of the patient’s general health status, and, in many cases, the oral lesions are the first sign of an HIV infection. Oral hairy leukoplakia (OHL) is a benign lesion of the oral mucosa related to Epstein-Barr virus (EBV) observed in HIV-positive individuals. The aim of this study was to report the contribution of oral cytopathology in the investigation of the HIV/AIDS status of patients as well as in the clinical and subclinical identification of OHL. Three patients were referred to the Oral Medicine Clinic in 2010. The patients were submitted to oral examination, and scrapes of the tongue were obtained. The Papanicolaou staining technique was used, and cytopathological analysis showed nuclear changes corresponding to cytopathic effects of EBV epithelial infection and candidiasis. The final diagnosis was OHL and candidiasis. Based on cytopathological diagnosis, an HIV serologic test was requested which revealed positive HIV serology. None of the patients was aware of their HIV serological status, and thus the cytopathology, by identifying OHL, contributed to the early diagnosis of HIV/AIDS. Cytopathology should be used as a routine procedure and it may be the method of choice for clinical and subclinical OHL diagnosis.
Fine Needle Aspiration Cytology of Kikuchi-Fujimoto’s Disease: A Report of 2 Cases with Emphasis on Cytologic Features and Differential Diagnosis
Authors: Sivakumar Sivaselvam , Ramamoorthy Ramkumar
Published: July 2012

Background: Kikuchi-Fujimoto’s disease (KFD) or histiocytic necrotizing lymphadenitis is an uncommon, benign, self-limited disease of unknown etiology, primarily affecting young women. Herein, we present the cytologic features of KFD of 2 cases that presented with different clinical pictures and discuss the cytologic differential diagnosis of this condition. Cases: Case 1 was a 17-year-old girl who presented with cervical lymphadenopathy since 6 weeks and case 2 was a 32-year-old female who had cough and axillary lymphadenopathy since 8 weeks. The fine needle aspiration (FNA) smears of both cases revealed a polymorphous lymphoid population intermingled with histiocytes, many of which showed a small size, eccentric location, crescent-shaped nuclei and abundant karyorrhectic debris in the background. A diagnosis of histiocytic necrotizing lymphadenitis was made on FNA cytology, which was confirmed by subsequent histologic examination of the lymph nodes. Conclusion: Precise diagnosis of KFD on cytologic smears is crucial as it can be mistaken for tuberculous lymphadenitis, systemic lupus erythematosus, malignant lymphoma or even metastatic carcinoma, and to avoid unnecessary investigations and potentially harmful treatment. With adequate, well-preserved samples and appropriate clinical setting, the presence of abundant karyorrhectic debris, crescentic macrophages, a polymorphous lymphoid population and absence of epithelioid cell granulomas, giant cells and neutrophils must alert the cytopathologist to arrive at a correct diagnosis.
Hairy Cell Leukemia Presenting as a Peripancreatic Mass: Cytomorphology and Radiographic Correlates
Authors: Subhawong A.P. , Subhawong T.K. , Ali S.Z.
Published: July 2012

Hairy cell leukemia (HCL) usually presents with peripheral cytopenias, diffuse marrow infiltration, and splenomegaly. This chronic lymphoproliferative disorder is not typically associated with lymphadenopathy or mass lesions. We report a case of HCL first treated by splenectomy, followed by several years of interferon therapy. Twenty-five years later, the patient presented with weight loss, fatigue, and a large PET-avid mass surrounding the head of the pancreas. Fine-needle aspiration was pursued to investigate the unusual and infiltrative appearance of the lesion, which was suggestive of another primary malignancy. Cytology smears showed discohesive lymphoid cells with round nuclei and delicate cytoplasmic projections. Flow cytometry confirmed the presence of a clonal B-cell population with bright expression of CD20 as well as CD25 and CD103, diagnostic of HCL. This is the first report of HCL presenting as a peripancreatic mass. The importance of correlation with radiology and clinical history is emphasized when evaluating such lesions.
Thyroid Transcription Factor 1 and Napsin A Double Staining in Lung Adenocarcinoma in Pleural Fluid
Authors: Liu Lian , Cohen Cynthia , Siddiqui Momin T.
Published: July 2012

Objective: Thyroid transcription factor 1 (TTF-1)/napsin A double staining is useful for the identification of primary lung adenocarcinoma. We examined its performance in pleural fluid. Study Design: Thirty-eight pleural-fluid specimens with lung adenocarcinoma were identified. Among these, 23 cases were diagnosed with a lung primary adenocarcinoma and 15 with a nonlung primary adenocarcinoma [breast (n = 13), ovarian (n = 1) and esophageal (n = 1)]. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded cell blocks. Expression of TTF-1 as a brown nuclear stain and napsin A as a red cytoplasmic stain were identified as positive staining. Results: In lung adenocarcinoma, 19 out of the 23 (83%) cases were positive for the TTF-1/napsin A double stain, 1 (4%) was positive for TTF-1 only, 2 (9%) were positive for napsin A only and 1 (4%) was negative for the TTF-1/napsin A double stain. All 15 cases of nonlung primary adenocarcinoma were negative for the TTF-1/napsin A double stain. Conclusion: The sensitivity of napsin A for diagnosing lung adenocarcinoma is slightly higher than that of TTF-1.
Morphological Variations in Microfilaria of Wuchereria bancrofti in Cytology Smears: A Morphometric Study of 32 Cases
Authors: Kaushal Seema , Iyer Venkateswaran K. , Mathur Sandeep R.
Published: July 2012

Objective: Microfilaria of Wuchereria bancrofti has been described in many cytological specimens, where typical blood film morphology has been used for evaluation. However, these studies have not documented the morphological variations in microfilaria in cytological smears. In the present study, cytological findings in 32 clinically unsuspected cases of filariasis were reviewed with emphasis on morphological details and image morphometric measurements. Study Design: A retrospective analysis of 32 cases of clinically unsuspected filariasis diagnosed by cytology from April 2001 to March 2011 was carried out. Results: All microfilariae were characterized as W. bancrofti and showed a wide variation in their length (202 to 300 µm) and width (6.2 to 8.4 µm). Terminal and subterminal swellings were seen in one of the cases causing diagnostic confusion with Brugia malayi. Microfilariae were shorter and wider in May-Grünwald-Giemsa stain than in Papanicolaou-stained smears. Conclusions: Natural variations in the size of microfilariae of W. bancrofti are the probable reason for the range of these findings. The overlapping features with microfilaria of B. malayi might be related to subspecies variations in W. bancrofti. Fixation, degeneration and staining procedure also seem to influence the morphological features. This morphometric study highlights the morphological disparities of microfilaria and the differential diagnostic considerations.
Cytologic and Immunophenotypic Features of CD34+ Stem Cells in Body Cavity Fluids
Authors: Kataoka Hideo , Okabe Hidetoshi , Amano Shigeru , Yamada Eiji , Ishida Mitsuaki , Kushima Ryoji , Kobayashi Tadao K.
Published: July 2012

Objectives: The possibility of leakage of CD34+ bone marrow stem cells from the peripheral blood into the coelomic cavity and the capability of coelomic fluid factors to induce their non-hematogenous differentiation were examined by immunocytochemistry (ICC). Study Design: Body cavity fluid smears from 12 and 18 patients with and without cancer, respectively, were processed for double immunoperoxidase or double fluorescent ICC methods using antibodies against CD34, CD14, CD16, CD68, AE1/AE3, epidermal growth factor receptor (EGFR), D2-40, and CA125. Results: Heavily irritated exudative fluid from 6 patients with or without cancer contained a few small round cells positive for CD34. Some of them co-expressed myeloid or monocytic markers such as CD14, CD68 or CD16. Some of the CD34+ cells also co-expressed AE1/AE3 or EGFR. In addition, D2-40 and CA125 were also demonstrated though the expression of the latter was quite sporadic. Conclusion: These findings support the concept that CD34+ stem cells can be released into irritated body cavity fluid and the possibility of subsequent differentiation to a non-hematogenous lineage under the influence of local humoral factors, in agreement with our previous in vitro experiments. The possibility of such a phenomenon should be kept in mind when body cavity fluid specimens are analyzed by ICC for diagnostic purposes.
The Utility of ‘Low-Grade Intraepithelial Lesion, Cannot Exclude High Grade’ Diagnosis: A Single Institution’s Experience
Authors: Finkelstein Alexander , Bajor-Dattilo Ewa B. , Yang Michael C. , Szeto Oliver , Zhou Fang , Elgert Paul , Das Kasturi
Published: July 2012

Objective: Squamous intraepithelial lesions (SILs) are classified as low-grade SIL (LGSIL) and high-grade SIL (HGSIL). ‘LGSIL cannot exclude high grade’ (LGSIL-H) interpretive category has been used in cases where findings exceed criteria for LGSIL, but do not fulfill the criteria for HGSIL. This study analyzed follow-up histology of LGSIL-H cases and compared the follow-up results of LGSIL-H with LGSIL to determine the utility of LGSIL-H category using a single institution’s experience. Study Design: Pap smears with LGSIL-H interpretation from 2005 to 2008 were retrieved. Histological follow-up results for LGSIL-H cases were analyzed and compared to the follow-up results of LGSIL cases. Results: Cases with LGSIL-H interpretation (311) comprised 0.18% of all cases (170,307). Follow-up was available for 144 patients and 13.2% had benign findings, 51.4% had cervical intraepithelial neoplasia (CIN) 1, and 35.4% had CIN 2 or higher. In comparison, of 425 patients with LGSIL, 22.6% had benign findings, 71% had CIN 1 and 6.4% had CIN 2 or higher. Conclusion: A significantly greater number of patients with LGSIL-H interpretation had a CIN 2 or higher lesion on follow-up compared to patients with LGSIL. This suggests LGSIL-H may be a useful diagnostic category.
Plant Food Allergy in Patients with Pollinosis from the Mediterranean Area
Authors: Flores E. , Cervera L. , Sanz M.L. , Diaz-Perales A. , Fernández J.
Published: July 2012

Background: Patients with pollinosis develop symptoms after intake of plant food more often than the general population. In order to study the prevalence of the presentation of allergic symptoms to plant foods in pollinosis, we selected a representative sample of the population from our Mediterranean area. Methods: All patients completed a questionnaire, provided a blood sample and underwent a battery of skin and other complementary tests (prick-prick, oral challenge test) when necessary. The pollen counts were obtained from the Elche pollen station. In addition, sera from a subgroup of patients were checked with an allergen molecule panel on an Advia Centaur XP platform. Results: Of the final sample (n = 233), 39.9% of the patients with pollinosis were sensitized and 30.9% had clinical allergy to at least one of the plant foods studied. Regression analysis showed that age and sensitization to the extracts of Platanus acerifolia and Artemisia vulgaris were the most important variables for discriminating between groups. Patients with pollinosis at a risk of allergy to plant foods had significantly higher Pru p 3 values [odds ratio (OR) 3.3; 95% confidence interval (95% CI) 2.3–4.8], and the value increased according to the number of plant food sensitizations. Conclusion: Plant food allergy is more common in patients with pollinosis than in the general population. The use of the London plain tree (P. acerifolia) and mugwort (A. vulgaris) in the skin tests may help identify such patients in our Mediterranean area, but determination of rPru p 3 could also be very useful in patients suspected of having plant food allergy.
Unique and Cross-Reactive T Cell Epitope Peptides of the Major Bahia Grass Pollen Allergen, Pas n 1
Authors: Etto Tamara , de Boer Carmela , Prickett Sara , Gardner Leanne M. , Voskamp Astrid , Davies Janet M. , O’Hehir Robyn E. , Rolland Jennifer M.
Published: July 2012

Background: Bahia grass pollen (BaGP) is a major cause of allergic rhinitis. Subcutaneous allergen-specific immunotherapy is effective for grass pollen allergy, but is unsuitable for patients with moderate to severe asthma due to the risk of anaphylaxis. T cell-reactive but IgE nonreactive peptides provide a safer treatment option. This study aimed to identify and characterize dominant CD4+ T cell epitope peptides of the major BaGP allergen, Pas n 1. Methods: Pas n 1-specific T cell lines generated from the peripheral blood of BaGP-allergic subjects were tested for proliferative and cytokine response to overlapping 20-mer Pas n 1 peptides. Cross-reactivity to homologous peptides from Lol p 1 and Cyn d 1 of Ryegrass and Bermuda grass pollen, respectively, was assessed using Pas n 1 peptide-specific T cell clones. MHC class II restriction of Pas n 1 peptide T cell recognition was determined by HLA blocking assays and peptide IgE reactivity tested by dot blotting. Results: Three Pas n 1 peptides showed dominant T cell reactivity; 15 of 18 (83%) patients responded to one or more of these peptides. T cell clones specific for dominant Pas n 1 peptides showed evidence of species-specific T cell reactivity as well as cross-reactivity with other group 1 grass pollen allergens. The dominant Pas n 1 T cell epitope peptides showed HLA binding diversity and were non-IgE reactive. Conclusions: The immunodominant T cell-reactive Pas n 1 peptides are candidates for safe immunotherapy for individuals, including those with asthma, who are allergic to Bahia and possibly other grass pollens.
Relationship between the Head Deviation Angle and Hemineglect in Patients with Right Hemisphere Stroke
Authors: Yang Tsung-Hsun , Hsin Yi-Jung , Liaw Mei-Yun , Wang Ho-Chen , Liang Pei-Jung , Leong Chau-Peng
Published: July 2012

Background: Patients with hemineglect have been reported to have abnormal head posture. We attempted to determine the extent to which the angles are correlated with the severity of hemineglect. Methods: In a prospective, single-center, cross-sectional study on 40 patients with single right hemisphere stroke, we evaluated left hemineglect severity using the line bisection and line cancellation tests. Head deviation angles were measured at admission and discharge using a head device containing 3 graduated discs that determined the angles of head deviation in the sagittal, coronal and transverse planes. Results: Head angles in the transverse and coronal planes differed significantly between the left hemineglect and non-hemineglect groups. Scores obtained from the line bisection and line cancellation tests correlated with these angles. Furthermore, improvement in left hemineglect after rehabilitation training corresponded to a reduction in the angles. Conclusion: Stroke patients with hemineglect exhibited significant head deviations in the transverse and coronal planes. Deviation angles correlated with hemineglect test scores.
Non-Small-Cell Lung Carcinoma Subtyping on Cytology without the Use of Immunohistochemistry – Can We Meet the Challenge?
Authors: Manucha Varsha , Wang Congli , Huang Yajue
Published: July 2012

Objective: Recent advances in lung carcinoma therapy have led to a new emphasis on the subtyping of non-small-cell carcinomas of the lung which has led pathologists to readdress the approach to small biopsies and cytology in lung cancer diagnosis. A minimum use of specimens for an accurate diagnosis and to preserve as much tissue as possible for potential molecular markers has been recommended. Study Design: In this study we blind-reviewed 50 cases of cytologically diagnosed non-small-cell type lung carcinomas and categorized them into adenocarcinoma and squamous-cell carcinoma based on cytological features alone. Only those cases that had had a histological follow-up were selected. Results: On blind review, a definitive categorization of non-small-cell carcinoma of the lung was made in 28 of 29 cases of adenocarcinomas and in 14 of 19 squamous-cell carcinomas. Conclusion: When attempted, most cases of well-to-moderately differentiated adenocarcinomas can be identified based on cytological features alone. Poorly differentiated squamous-cell carcinomas are more likely to be called non-small-cell carcinomas.
Heavy Cervical Cancer Burden in Elderly Women: How Can We Improve the Situation?
Authors: Skaznik-Wikiel Malgorzata E. , Sukumvanich Paniti , Austin R. Marshall , Zorn Kristin K. , Krivak Thomas C. , Edwards Robert P. , Olawaiye Alexander B.
Published: July 2012

Objectives: The American Cancer Society, the American College of Obstetricians and Gynecologists and the US Preventive Services Task Force recommend discontinuation of cervical cancer screening between 65 and 70 years of age in women with no abnormal test results in the preceding 10 years. This population-based study was undertaken to determine the incidence of cervical cancer in different age groups as a means to establish if current screening recommendations need reevaluation. Study Design: Data from the SEER database were used to compute incidence rates for cervical cancer diagnosed between 2000 and 2006 by age and disease stage. Results: We identified 18,003 women with cervical cancer. 12.18% were above the age of 69. The incidence in this age group was 8.7/100,000. Women younger than 30 comprised 5.7% of patients with an incidence of 5/100,000 and were most commonly diagnosed with stage IA1 disease. Women above 70 were most frequently diagnosed with stage IIIB. 79% of patients younger than 30 were diagnosed with an early disease (stage IA1–IIA) as opposed to only 41.2% of patients aged 69 or above. Conclusions: The incidence of cervical cancer does not decrease significantly in older women. Women over the age of 70 are frequently diagnosed with advanced stage disease which limits their treatment options. Failure to apply uniform screening across all at-risk age groups may account for the discrepancy.
Diagnostic Pitfalls of Hashimoto’s/Lymphocytic Thyroiditis on Fine-Needle Aspirations and Strategies to Avoid Overdiagnosis
Authors: Harvey Aaron M. , Truong Luan D. , Mody Dina R.
Published: July 2012

Objective: The importance of identifying papillary carcinoma or lymphoma amidst background Hashimoto’s/lymphocytic thyroiditis (H/LT) is well documented. However, avoidance of overdiagnosing neoplasms on thyroid fine-needle aspiration (FNA) with only H/LT has not been adequately addressed. Study Design: This study aimed to identify cytomorphologic features leading to overdiagnosing neoplasms within background H/LT. Nine thyroid FNAs classified as suspicious or positive for neoplasm with subsequent thyroidectomy specimens having only H/LT were identified. Cytologic features of these cases were compared to 8 control cases from the same time period and FNAs from both groups were reevaluated for features from the cytology literature. Results: Features leading to overdiagnosing papillary carcinoma were: powdery chromatin, occasional nuclear grooves or holes, and paucity of background lymphocytes. One feature differentiating H/LT from neoplasm noted in most cases was lymphocytes infiltrating follicular groups. In contrast, true papillary carcinomas displayed characteristic features in multiple cell clusters. These clusters were devoid of infiltrating lymphocytes or displayed only rare lymphocytes at their periphery. A microfollicular pattern with paucity of background lymphocytes was the major pitfall in overdiagnosing follicular neoplasm. Conclusions: Features suspicious for neoplasm are often seen in FNA of H/LT, leading to unnecessary surgery. Recognizing this pitfall and its differentiating features should avert overdiagnosis.
A Rare Case of a Male with 45, XO, SRY+, ZFY+ with Short Stature and Mild Turner Stigmata
Authors: Ntali Georgia , Sofocleous Christalena , Kouvidi Elisabeth , Tsagaraki Georgia , Dolianiti Maria , Kaimara-Papathanasiou Asteroula , Fryssira Helen
Published: July 2012

Background: Turner syndrome is hypothesized to result from haploinsufficiency of certain genes expressed from both sex chromosomes that escape X inactivation. Case Report: We present the rare case of a 4-year-old boy who was referred to the pediatric endocrinology unit for evaluation of slight growth delay. Results: Standard cytogenetic analysis showed a 45,XO karyotype. Molecular studies disclosed the presence of an intact SRY homeobox region and the ZFY region sited on the Y short arm. Other Y chromosome sequences which are normally found on the short arm of chromosome Y (p) were absent and their exact location on a different chromosome remained unclear. Subsequently, FISH (fluorescent in situ hybridization) analysis failed to detect any Y sequences, while haplotype analysis indicated that the present X chromosome was of paternal origin. Conclusion: Phenotype-genotype correlation studies were consistent with a male patient presenting with short stature and some of the Turner’s syndrome stigmata. The consequences for the patients with this chromosomal abnormality and treatment with recombinant growth hormone are also discussed.
Insight into New Potential Targets for the Treatment of Overactive Bladder and Detrusor Overactivity
Authors: Cerruto M.A. , Asimakopoulos A.D. , Artibani W. , Del Popolo G. , La Martina M. , Carone R. , Finazzi-Agrò E.
Published: July 2012

Although overactive bladder (OAB) and detrusor overactivity (DO) are not synonyms, they share therapeutic options and partially underlying physiopathological mechanisms. The aim of this overview is to give insight into new potential targets for the treatment of OAB and DO. A narrative review was done in order to reach this goal. Ageing, pelvic floor disorders, hypersensitivity disorders, morphologic bladder changes, neurological diseases, local inflammations, infections, tumors and bladder outlet obstruction may alter the normal voluntary control of micturition, leading to OAB and DO. The main aim of pharmacotherapy is to restore normal control of micturition, inhibiting the emerging pathological involuntary reflex mechanism. Therapeutic targets can be found at the levels of the urothelium, detrusor muscles, autonomic and afferent pathways, spinal cord and brain. Increased expression and/or sensitivity of urothelial-sensory molecules that lead to afferent sensitization have been documented as a possible pathogenesis of OAB. Targeting afferent pathways and/or bladder smooth muscles by modulating activity of ligand receptors and ion channels could be effective to suppress OAB.
Intrafascial Dissection Significantly Increases Positive Surgical Margin and Biochemical Recurrence Rates after Robotic-Assisted Radical Prostatectomy
Authors: Mortezavi Ashkan , Hermanns Thomas , Seifert Hans-Helge , Wild Peter J. , Schmid Daniel M. , Sulser Tullio , Eberli Daniel
Published: July 2012

Introduction: Improved visualization and magnification in robot-assisted laparoscopic radical prostatectomy (RALRP) has tempted many urologists to dissect the neurovascular bundle closer to the prostate following the layers of the pseudo-capsule of the prostate. This might bear a higher risk of decreased tumor control. Materials and Methods: An analysis of a consecutive series of 186 patients who underwent RALRP at our institution was performed. The outcome of patients with intrafascial nerve-sparing (INS) was compared with the outcome of patients who underwent interfascial, extrafascial or no nerve-sparing (non-INS). Results: A total of 80 patients (43.0%) received INS. The overall R1 rate was 27.9%. For pT2 tumors the rate of R1 was 33.8% in INS versus 14.8% in non-INS (odds ratio 2.936, 95% confidence interval 1.338–6.443, p = 0.007). Recurrence-free survival was significantly shorter in INS (p = 0.05; hazard ratio 3.791). Conclusion: The intrafascial dissection technique for RALRP bears a high risk of incomplete resection in localized prostate cancer resulting in unfavorable outcome.
In vitro Activity of Tigecycline and Molecular Characterization of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates from a University Hospital in South-Western Germany
Authors: Wienke Matthias , Pfeifer Yvonne , Weissgerber Patrick , Marschal Matthias , Autenrieth Ingo B. , Gröbner Sabine
Published: July 2012

Background: Extended-spectrum β-lactamase (ESBL)-producing organisms are spreading worldwide in hospital and community settings. Methods: A total of 328 unduplicated ESBL-producing Enterobacteriaceae isolated in 2008 and 2009 at the University Hospital of Tübingen were analysed retrospectively. Results:Escherichia coli (n = 253) and Klebsiella spp. (n = 46) were the most frequent ESBL-producing species. The ESBL rates among E. coli and Klebsiella spp. increased from 3.8 and 2.1%, respectively, in 2008, to 5.2 and 2.4%, respectively, in 2009. Two E. coli and 3 Klebsiella pneumoniae ESBL producers were non-susceptible to ertapenem, most likely due to loss of porins. Antimicrobial susceptibility testing of selected, molecularly characterized ESBL producers revealed susceptibility to tigecycline among 97.9% (191/195) of the E. coli and 78.8% (26/33) of the K. pneumoniae isolates. PCR analysis and sequencing showed the presence of CTX-M-type enzymes in 91.3% of the E. coli and 87.9% of the K. pneumoniae isolates, whereby blaCTX-M-15 was the most frequent ESBL gene both in E. coli (50.0%) and K. pneumoniae (51.5%). Only 7 single cases of potential patient-to-patient transmissions of E. coli strains were observed. Conclusions: Our data suggest that the increase in ESBL-producing E. coli and K. pneumoniae isolates at our hospital is mainly caused by growing import of Enterobacteriaceae harbouring CTX-M-type ESBLs.
Molecular Analysis of Centrifugation Supernatant Fluid from Pancreaticobiliary Duct Samples Can Improve Cancer Detection
Authors: Finkelstein Sydney D. , Bibbo Marluce , Loren David E. , Siddiqui Ali A. , Solomides Charalambos , Kowalski Thomas E. , Ellsworth Eric
Published: July 2012

Objective: We aimed to supplement microscopic examination of biliary cytobrush specimens to improve sensitivity by mutational profiling of: (1) selected cells microdissected from cytology slides and (2) corresponding cell-free DNA in residual supernatant fluid. Study Design: From 43 patients with brushings of bile or pancreatic duct strictures, DNA was extracted from microdissected cells and 1–2 ml of cytocentrifugation supernatant fluid. Mutational analysis targeted 17 genomic sites associated with pancreaticobiliary cancer, including sequencing for KRAS point mutation and loss of heterozygosity (LOH) analysis of microsatellites located at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 21q, and 22q. Results: Mutations were found in 25/28 patients with malignancy, and no mutations were found in 5/5 patients with benign surgical results. The cell-free supernatant fluid generally contained higher levels and quality of DNA, resulting in increased detection of mutations in most patients. KRAS mutations only occurred in patients with pancreatic cancer. Mutational profiling of supernatant fluid specimens resulted in high sensitivity and specificity for malignancy, improving the detection of malignancy over cytology alone. Conclusion: Brush cytology specimens yielded supernatant fluid enriched with DNA, probably from actively proliferating cells. Mutational profiling can enhance the cytologic evaluation and characterization of specimens suspected to contain pancreatic or bile duct cancer.
Fast Intraoperative Testosterone Assay Confirms the Location of an Ovarian Virilizing Tumor in a Young Girl
Authors: Braun R. , Peter A. , Warmann S. , Fuchs J. , Binder G.
Published: July 2012

The detection of testosterone-producing ovarian tumors in childhood and adolescence by imaging techniques only can be difficult because of the tumors' radiological structure and sometimes diminutive size. We describe an 11.5-year-old girl with a 9-month history of voice deepening, mild hirsutism, minor acne, increased growth velocity, weight gain, and clit-oromegaly. Laboratory investigation revealed an extremely elevated serum testosterone level without any additional endocrine abnormalities. Abdominal ultrasound and MRI showed a sparsely noticeable solid mass in the center of the right ovary. At laparotomy, blood was selectively drawn from the right and the left ovarian veins. Rapid testosterone measurement revealed a 70-fold higher testosterone concentration in the right ovarian vein within 45 min. Based on this finding, a right salpingo-oophorectomy was performed. The patient's postoperative testosterone level declined within 24 h. The histopathological diagnosis was Leydig cell tumor. In conclusion, the implementation of a fast intraoperative testosterone assay enabled the localization and curative therapy of a Leydig cell tumor. This technique seems to be a good alternative to preoperative selective venous blood sampling when body imaging does not unveil the tumor's site.
Effect of Imidafenacin on Nocturia and Sleep Disorder in Patients with Overactive Bladder
Authors: Wada Naoki , Watanabe Masaki , Kita Masafumi , Matsumoto Seiji , Osanai Hiroaki , Yamaguchi Satoshi , Numata Atsushi , Fujisawa Makoto , Saga Yuji , Hou Kyokushin , Iuchi Hiromitsu , Niibori Daisuke , Kura Tatsuhiko , Taniguchi Akihisa , Kunieda Manabu , Nakata Yasunobu , Kakizaki Hidehiro
Published: July 2012

Objective: To evaluate the efficacy of imidafenacin on nocturia and sleep disorder in patients with overactive bladder (OAB). Patients and Methods: A prospective multicenter study of imidafenacin 0.1 mg twice daily for patients with OAB and nocturia was conducted. At baseline and at week 4 and 8, patients were assessed using the overactive bladder symptom score (OABSS), frequency volume charts (FVC) and the Pittsburgh Sleep Quality Index (PSQI). Results: Treatment with imidafenacin significantly improved OAB symptoms. Imidafenacin also improved PSQI, especially subjective sleep quality, sleep latency and daytime dysfunction. In FVC, the number of daytime voids and nighttime voids significantly decreased and average voided volume significantly increased after imidafenacin. Subanalysis of FVC based on the patients’ age revealed that nocturnal polyuria was more often found in patients aged 75 years or over than in those aged under 75 years (79 vs. 55%, p < 0.05). Treatment with imidafenacin significantly reduced the nocturnal polyuria index only in patients aged 75 years or over. Conclusions: Imidafenacin can improve nocturia and sleep disorder in patients with OAB. The efficacy of imidafenacin on nocturia is attributable to an increase in bladder capacity and a decrease in nocturnal urine volume. We conclude that imidafenacin is an effective and safe drug for nocturia in patients with OAB.
Incomplete Healing of the Uterine Incision after Cesarean Section: Is It Preventable by Intraoperative Digital Dilatation of the Internal Cervical Ostium?
Authors: Yazicioglu Hasan Fehmi , Sevket Osman , Ekin Murat , Ozyurt Osman , Aygun Mehmet
Published: July 2012

Background/Aims: It was the aim of this study to determine if intraoperative digital dilatation of the closed internal cervical ostium affects the healing of the uterine scar after a cesarean section (CS). Methods: In this randomized, prospective study, 94 term pregnant patients who elected to have a CS were assigned to two groups: intraoperative digital dilatation of the internal cervical ostium (group I, n = 48) or no dilatation (group II, n = 46). Vaginal ultrasound was used to check the integrity of the cesarean scar at the uterine incision site 40–42 days after the operation. We calculated the healing ratio based on ultrasonographic results and compared the groups as to the amount of incomplete healing. Results: The frequency of abnormal scarring was significantly higher in group II (14.3 vs. 40.6%; p < 0.05). The mean healing ratio was significantly higher in group I (0.95 ± 0.12) than in group II (0.87 ± 0.1; p < 0.05). In the multiple logistic regression model, digital dilatation remained the most significant factor affecting abnormal scar formation (odds ratio = 7.7). Conclusion: Digital dilatation of a closed cervix in elective CS might lower the incidence of abnormal scarring of the uterine incision.
The Bethesda System for Reporting Thyroid Cytopathology: A Meta-Analysis
Authors: Bongiovanni Massimo , Spitale Alessandra , Faquin William C. , Mazzucchelli Luca , Baloch Zubair W.
Published: July 2012

Objective: We aimed to investigate the validity of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) through meta-analysis. Study Design: All publications between January 1, 2008 and September 1, 2011 that studied TBSRTC and had available histological follow-up data were retrieved. To calculate the sensitivity, specificity and diagnostic accuracy, the cases diagnosed as follicular neoplasm, suspicious for malignancy and malignant which were histopathologically confirmed as malignant were defined as true-positive. True-negative included benign cases confirmed as benign on histopathology. The nondiagnostic category was excluded from the statistical calculation. The correlations between the 6 diagnostic categories were investigated. Results: The publications review resulted in a case cohort of 25,445 thyroid fine-needle aspirations, 6,362 (25%) of which underwent surgical excision; this group constituted the basis of the study. The sensitivity, specificity and diagnostic accuracy were 97, 50.7 and 68.8%, respectively. The positive predictive value and negative predictive value were 55.9 and 96.3%, respectively. The rates of false negatives and false positives were low: 3 and 0.5%, respectively. Conclusions: The results of meta-analysis showed high overall accuracy, indicating that TBSRTC represents a reliable and valid reporting system for thyroid cytology.
A Diagnostic Algorithm for Mitochondrial Disorders in Estonian Children
Authors: Joost K. , Rodenburg R.J. , Piirsoo A. , van den Heuvel L. , Žordania R. , Põder H. , Talvik I. , Kilk K. , Soomets U. , Õunap K.
Published: July 2012

Mitochondrial disorders are a heterogeneous group of disorders affecting energy production of the body. Different consensus diagnostic criteria for mitochondrial disorders in childhood are available – Wolfson, Nijmegen and modified Walker criteria. Due to the extreme complexity of mitochondrial disorders in children, we decided to develop a diagnostic algorithm, applicable in clinical practice in Estonia, in order to identify patients with mitochondrial disorders among pediatric neonatology and neurology patients. Additionally, it was aimed to evaluate the live-birth prevalence of mitochondrial disorders in childhood. During the study period (2003–2009), a total of 22 children were referred to a muscle biopsy in suspicion of mitochondrial disorder based on the preliminary biochemical, metabolic and instrumental investigations. Enzymatic and/or molecular analysis confirmed mitochondrial disease in 5 of them – an SCO2 gene (synthesis of cytochrome c oxidase, subunit 2) defect, 2 cases of pyruvate dehydrogenase complex deficiency and 2 cases of combined complex I and IV deficiency. The live-birth prevalence for mitochondrial defects observed in our cohort was 1/20,764 live births. Our epidemiological data correlate well with previously published epidemiology data on mitochondrial diseases in childhood from Sweden and Australia, but are lower than in Finland.
MOTA Syndrome: Molecular Genetic Confirmation of the Diagnosis in a Newborn with Previously Unreported Clinical Features
Authors: Mitter D. , Schanze D. , Sterker I. , Müller D. , Till H. , Zenker M.
Published: July 2012

MOTA syndrome, the acronym for Manitoba-oculo-tricho-anal syndrome (OMIM 248450), is a distinct autosomal recessive multiple malformation syndrome caused by mutations in the FREM1 gene (OMIM 608944). Eight patients with MOTA syndrome and a pathogenic FREM1 mutation have previously been documented. We report on a new male patient, 3.5 months old, with MOTA syndrome, who presented with the following features: bilateral incomplete cryptophthalmos with a completely fused, ill-defined upper eyelid and a keratinized cornea, hypertelorism, a broad tip of the nose, a circle-shaped whirl of hair on the forehead, and a low anorectal malformation, which could be corrected on day 2 of life without a colostomy. In expansion to the previously reported phenotype of MOTA syndrome, the patient showed characteristic features reported in patients with Fraser syndrome, including dysplastic ears, cutaneous syndactyly 3/4 of the hands and syndactyly 2/3 of the right foot. Molecular analysis of FREM1 identified compound heterozygosity for a new frameshift deletion in exon 24 (c.4629delC, p.F1544SfsX62) and a previously reported missense mutation in exon 21 (c.3971T>G, p.L1324R). This report further extends the phenotype of MOTA syndrome and underscores the overlapping clinical spectrum of FRAS-FREM complex diseases.
Operator Versus Core Laboratory Assessment of Angiographic Reperfusion Markers in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction
Authors: Brener Sorin J. , Cristea Ecaterina , Lansky Alexandra J. , Fahy Martin , Mehran Roxana , Stone Gregg W.
Published: July 2012

Background—

Thrombolysis In Myocardial Infarction (TIMI) flow and Myocardial Blush Grade (MBG) are important prognostic indicators before and after primary percutaneous coronary intervention (PCI) in ST-segment–elevation myocardial infarction; however, the concordance and relative prognostic utility of operator (Op) versus angiography core laboratory (ACL) assessed TIMI flow and MBG are unknown.

Methods and Results—

Baseline and final Op and ACL TIMI flow and MBG assessment were compared from the Harmonizing Outcomes with RevascularIZatiON and Stents in AMI trial in 3345 patients undergoing primary PCI using Cohen’s
κ
coefficient.
κ
Was highest for pre-PCI TIMI flow (0.51, representing moderate agreement) and lowest for post-PCI MBG (0.20, representing fair agreement). Discordance between Op and ACL for final TIMI flow (0 to 2 versus 3) occurred in 12.9% of patients and for final MBG (0 to 1 versus 2 to 3) in 22.4%. Among 415 patients with final TIMI flow 0 to 2 by ACL, Op scoring was TIMI flow 3 in 267 (64.3%). Similarly, among 706 patients with final MBG 0 to 1 by ACL, 563 (79.7%) were classified as MBG 2 to 3 by Op. Post-PCI TIMI 3 flow and MBG 2 to 3 strongly correlated with 3-year survival, as assessed by both Op and ACL (
P
<0.0001). Mortality was intermediate in patients in whom ACL and Op were discordant, without marked prognostic differences between the discordant groups.

Conclusions—

Op and ACL assessment of angiographic markers of reperfusion in ST-segment–elevation myocardial infarction demonstrates fair to moderate agreement. Op tended to favorably grade unfavorable ACL results. Nonetheless, both Op and ACL assessment of reperfusion strongly inform prediction of 3-year mortality.
Near-Term Fetal Hypoxia–Ischemia in Rabbits
Authors: Drobyshevsky Alexander , Derrick Matthew , Luo Kehuan , Zhang Li-Qun , Wu Yi-Ning , Takada Silvia Honda , Yu Lei , Tan Sidhartha
Published: July 2012

Background and Purpose—

The pattern of antenatal brain injury varies with gestational age at the time of insult. Deep brain nuclei are often injured at older gestational ages. Having previously shown postnatal hypertonia after preterm fetal rabbit hypoxia–ischemia, the objective of this study was to investigate the causal relationship between the dynamic regional pattern of brain injury on MRI and the evolution of muscle tone in the near-term rabbit fetus.

Methods—

Serial MRI was performed on New Zealand white rabbit fetuses to determine equipotency of fetal hypoxia–ischemia during uterine ischemia comparing 29 days gestation (E29, 92% gestation) with E22 and E25. E29 postnatal kits at 4, 24, and 72 hours after hypoxia–ischemia underwent T2- and diffusion-weighted imaging. Quantitative assessments of tone were made serially using a torque apparatus in addition to clinical assessments.

Results—

Based on the brain apparent diffusion coefficient, 32 minutes of uterine ischemia was selected for E29 fetuses. At E30, 58% of the survivors manifested hind limb hypotonia. By E32, 71% of the hypotonic kits developed dystonic hypertonia. Marked and persistent apparent diffusion coefficient reduction in the basal ganglia, thalamus, and brain stem was predictive of these motor deficits.

Conclusions—

MRI observation of deep brain injury 6 to 24 hours after near-term hypoxia–ischemia predicts dystonic hypertonia postnatally. Torque-displacement measurements indicate that motor deficits in rabbits progressed from initial hypotonia to hypertonia, similar to human cerebral palsy, but in a compressed timeframe. The presence of deep brain injury and quantitative shift from hypo- to hypertonia may identify patients at risk for developing cerebral palsy.
Statin Use and Microbleeds in Patients With Spontaneous Intracerebral Hemorrhage
Authors: Haussen Diogo C. , Henninger Nils , Kumar Sandeep , Selim Magdy
Published: July 2012

Background and Purpose—

Statins have been associated with increased risk of intracerebral hemorrhage (ICH), particularly in elderly patients with previous ICH. Recurrent ICH in the elderly is often related to cerebral amyloid angiopathy. Therefore, we investigated whether statin use is associated with increased prevalence and severity of microbleeds (MB), particularly cortico-subcortical microbleeds (csMB), which are frequently observed in cerebral amyloid angiopathy.

Methods—

We studied 163 consecutive patients with spontaneous ICH who underwent magnetic resonance imaging within 30 days of presentation. We retrieved clinical information and analyzed magnetic resonance imaging for the presence, location, and number of MB, which were divided into csMB or other (other MB). We performed group comparisons stratified by statin use and by the presence vs absence of any MB (csMB and/or other MB) or csMB alone.

Results—

Sixty-four percent had lobar ICH. Overall, 53% had microbleeds and 39% had csMB. Statin users were older, had significantly lower cholesterol and low-density lipoprotein levels, and higher prevalence of hypertension, diabetes, dyslipidemia, and antiplatelet use. The prevalence and number of other MB were similar in statin-treated and statin-untreated individuals. However, more statin-treated patients had csMB (57% vs 33%;
P
=0.007), with almost twice as many lesions (4.6±11.3 vs 2.4±8.0;
P
=0.007) compared with untreated patients. Age and statin use were independently associated with both the presence and increased number of MB (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00–1.05;
P
=0.01 and OR, 2.72; 95% CI. 1.02–7.22;
P
=0.04, respectively) and csMB (OR, 1.03; 95% CI, 1.00–1.06;
P
=0.01 and OR, 4.15; 95% CI, 1.54–11.20;
P
<0.01) in multivariate analyses.

Conclusions—

Statin use in patients with ICH is independently associated with MB, especially csMB. Future studies are needed to confirm our findings and to investigate whether csMB can serve as a surrogate marker for ICH risk in statin-treated patients.