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Background Body fluid cytology (BFC) is an important tool in the diagnosis and staging of malignancy and is aided by the judicious use of immunohistochemistry (IHC). The aim of this study was to determine the usage rates of IHC stains in BFC, their type and indications, and their diagnostic impact. We also attempted to estimate the optimal rate of IHC use in BFC by comparing the entire laboratory's and each individual cytopathologist's IHC use rates with their respective indeterminate and malignant diagnosis rates. Methods We conducted a retrospective study of IHC stain use in BFC during a 5.5-year interval (2013-2018) and determined the laboratory's and each individual cytopathologist's IHC usage patterns according to the final diagnosis, site, and indications for their use. Results A total of 477 out of 4144 (11.5%) BFC cases had 2128 individual immunostains performed, with an average of 4.5 immunostains per case. Individual cytopathologists used IHC stains on 6.7% to 22% of their BFC cases. Pathologists with higher rates of IHC stain use than the laboratory's mean were less experienced and had higher rates of indeterminate but not of malignant diagnoses. The most common indication for the use of IHC stains was differentiating mesothelial from malignant cells. MOC31, calretinin, Ber-EP4, CD68, and D2-40 were the most commonly used of the 67 different IHC stains used in BFC. Conclusions The laboratory's mean may represent the optimal IHC use rate, as higher IHC use rates did not lead to more diagnostic certainty or higher pickup rates of malignant cells.

BACKGROUND The Centers for Disease Control and Prevention recommends screening baby boomers and high-risk patients for hepatitis C virus (HCV); however, the incidence of HCV is rapidly increasing among younger populations, and screening is limited by access to care and risk factor assessment. The purpose of this study was to evaluate characteristics of HCV antibody-positive (Ab+) and ribonucleic acid (RNA)-confirmed-positive patients identified via two screening models in an Appalachian emergency department (ED). METHODS This was a retrospective cohort study of patients who screened HCV Ab+ in the ED from January 1 to October 31, 2018. Data were extracted, and comparative analyses were conducted between the risk-based and the universal screening models. RESULTS Overall, 444 patients screened HCV Ab+, with a median age of 39 years. From January to May 2018, the risk factor model identified 126 HCV Ab+ patients out of 3,014 screened (4%), whereas from June to October 2018, the universal model identified 318 HCV Ab+ patients out of 5,407 screened (6%; p

STUDY OBJECTIVE Access to naloxone is a priority for reducing opioid deaths. Although community members who complete naloxone training are able to administer nasal naloxone successfully and rapidly, little is known about the ability of community members to administer naloxone without training. The objective of this study was to assess the ability of untrained individuals to administer naloxone successfully in a simulated opioid overdose setting. DESIGN Prospective single-site open-label randomized usability assessment. SETTING Scenario station at a large state fair during August and September 2017. PARTICIPANTS A total of 207 healthy adults who were randomly assigned to administer naloxone using a nasal spray (NS) device (69 participants), an intramuscular (IM) kit (68 participants), or an improvised nasal atomizer (AT) kit (70 participants). INTERVENTION Participants were instructed to administer the device to a high-fidelity mannequin in a public environment with distractions to mimic those that might be present in an actual overdose. No device instructions or administration materials were provided. MEASUREMENTS AND MAIN RESULTS Participants were assessed by trained study team members who directly observed all naloxone administrations using the predetermined end-point criteria. Individual participant perceptions were evaluated immediately following the naloxone administration using a standardized questionnaire form. The primary outcome was successful administration, defined as administration within 7 minutes and without critical errors. Secondary outcomes were time to successful naloxone administration and ease of use of the device. The NS (66.7%, p

Background Urinary tract cytology (UTCy) is used for screening urothelial carcinoma (UC) and it must have a high negative predictive value (NPV) to be an effective test. To the authors' knowledge, the literature regarding the NPV of UTCy provides little information regarding the risk of malignancy, especially for patients with high-grade urothelial carcinoma (HGUC). Methods Patients with negative UTCy specimens were identified in the pathology files at the study institution for the years 2012 through 2013. Cases were deemed true-negative cases if there was at least 1 subsequent negative specimen or negative clinical follow-up within 6 months of the index case. False-negative cases were defined as HGUC or carcinoma in situ by surgical biopsy and/or any UTCy with suspicious for HGUC or HGUC follow-up. Results A total of 2614 UTCy specimens from 2089 patients were identified. There was a disease prevalence of 6.5%. There were 87 false-negative results for HGUC, which corresponded to an overall NPV of 96.7%. When categorized by clinical indication, hematuria resulted in the highest NPV of 99.5% followed by other indications (97.7%) and a history of UC (90.1%). When categorized by the specimen type, voided urine specimens were found to have the highest NPV of 98.7% followed by other indications (96.9%) and washing specimens (96.2%). Of the 717 patients with a history of UC, the NPV was lower for washing specimens (89.8%) than for voided urine specimens (96.2%). When including either low-grade urothelial carcinoma or HGUC as a positive follow-up, the NPV dropped to 93.3% from 96.7% (HGUC only). The sensitivity of the diagnostic category of atypical urothelial cells or higher was 93.0%. Conclusions Overall, UTCy appears to have a good NPV and a high sensitivity for HGUC. The clinical indication had a greater impact on NPV compared with the specimen type.

BACKGROUND AND AIMS Expanded access to naloxone has been identified as a key intervention for reducing opioid-related morbidity and mortality. It is not known which naloxone device will result in rapid, successful administration when administered by community members. The aims of this study were to estimate and compare (1) the rate of successful administration and (2) time to successful administration for single-step nasal spray, multi-step atomized nasal spray and intramuscular simulated naloxone by community members. DESIGN A prospective, single-site, open-label, randomized usability assessment of simulated naloxone administration in a convenience sample of community members. Participants were randomized to single-step nasal spray (SP), multi-step atomized nasal spray (AT) or intramuscular simulated (IM) naloxone and asked to administer the simulated medication to a mannequin after completing a 2-minute training video. SETTING New York, USA at a state fair that attracts between 60 000 and 120 000 individuals daily. PARTICIPANTS A total of 138 participants completed the study over a 2-day period in September 2016. All participants were at least 18 years of age and had no prior naloxone training. MEASUREMENTS The rate of successful administration and time to successful administration were recorded for each device. FINDINGS The SP device (100%; P

BACKGROUND The aim of this study was to evaluate the potential use of the UroVysion® fluorescent in situ hybridization test (U-FISH) to stratify the risk of urothelial carcinoma (UC) in patients with a diagnosis of "atypical urothelial cells" (AUC) in urinary tract cytology (UTCy). METHODS Using a histologic diagnosis of UC and respectively of high grade UC (HGUC) within 12 months of the index UTCy as a reference standard, we determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of U-FISH for patients with AUC diagnosed 2008 to 2014. RESULTS Of the 377 patients with AUC, 62 (16.45%) were diagnosed with UC (29 low grade UC and 33 HGUC) within 12 months. U-FISH were uninformative in 45 (11.94%), positive in 63 (16.71%) and negative in 269 (71.35%). UC was diagnosed more frequently in patients with positive than in those with negative U- FISH results (31/63, 49.21% vs. 25/269, 9.29%, P

Indeterminate cytologic diagnoses in endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) of solid pancreatic lesions include the diagnostic categories “atypical” (ATY) and “suspicious for malignancy” (SUSP), which are used at variable rates and are associated with variable underlying risk of malignancy. The aim of this study was to determine individual cytopathologists' rates of indeterminate diagnoses in EUS-FNA of solid pancreatic lesions and their relationship to cytopathologists' experience and volume of pancreatic EUS-FNA examined, as well as the potential impact of departmental consensus review on indeterminate diagnoses. Design The diagnostic rates of ATY and SUSP and their underlying risk of malignancy were calculated for six cytopathologists who diagnosed 1,114 of 1,225 EUS-FNA of solid pancreatic lesions from 1/1/2001 to 9/15/2014, and were then compared for the periods before and after the implementation of departmental consensus review during 2009. Results The six cytopathologists diagnosed 10% of cases as indeterminate; 82 (7.4%) as “atypical” and 29 (2.6%) as “suspicious”. The individual cytopathologists' indeterminate diagnosis rates varied twofold (6.67–12.80%) and did not correlate with their experience, total or annual volume of EUS-FNAs. Of the 56/99 (56.57%) cases with follow-up, the underlying rate of malignancy was 47% (35/75; for “atypical” and 87.5% (21/24); for “suspicious”). The underlying rates of malignancy were 33–67% for “atypical” and 80–100% for “suspicious” diagnoses made by individual cytopathologists. The rate of indeterminate diagnoses decreased from 11.55 to 7.88% after the implementation of departmental consensus review. Conclusion Individual cytopathologists' rates of indeterminate diagnoses and their significance vary; however, consensus review is helpful in reducing these rates. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

BACKGROUND “The Paris System” proposes a 7-tier classification system for urine cytology. Establishing the risk of malignancy (ROM) associated with these diagnostic categories is essential to determine the appropriate management of patients. The objective of this study was to determine the ROM associated with the “positive” and “suspicious” categories. METHODS The authors searched their electronic records for urine cytology specimens that had been diagnosed as “positive” or “suspicious” for high-grade urothelial carcinoma within an 11-year time frame. Then, the ROM was determined for these specimens within a 6-month follow-up interval. The cytologic diagnoses were correlated with surgical biopsy results, follow-up cytology results, and/or fluorescence in situ hybridization (FISH) results. RESULTS In total, 662 specimens (487 “positive” and 175 “suspicious”), corresponding to 387 patients (295 men and 92 women), were included. The majority of specimens were collected by bladder washing (568 of 662 specimens; 85.4%) and for the indication of surveillance (601 of 662 specimens; 82%). On follow-up, bladder washing specimens were positive more often positive than voided urine specimens (466 of 570 [81.8%] vs 60 of 92 [65.2%]; P = .0005), and surveillance specimens were more often positive than specimens collected for other indications (82% vs 54.1%). The overall positive predictive value was higher for positive specimens than for suspicious specimens (365 of 461 [79.2%] vs 83 of 150 [55.3%]; P

BACKGROUND After radical cystectomy and urinary diversion (RC-UD), upper urinary tract and urethral recurrences of urothelial carcinoma (UCa) are reported to occur in 2% to 17% of patients. The objective of the current study was to determine the performance of urinary cytology (UCy) in the diagnosis of recurrences in the remnant urothelium (RRU) after RC-UD. METHODS The authors retrospectively identified all patients who underwent RC-UD for UCa at the study institution from January 2002 to April 2014, and collected data from all available follow-up UCy and biopsies. Cytologies were classified as unsatisfactory, negative, suspicious, positive for malignancy, or atypical urothelial cells (AUC). The authors calculated the sensitivity, specificity, positive predictive value, and negative predictive value of suspicious or positive UCy for the diagnosis of histologically confirmed RRU. RESULTS Of the 222 patients who underwent RC-UD for UCa of the urinary bladder during the study period, 111 had at least 1 follow-up UCy performed at the study institution, for a total of 477 UCy samples. During a mean follow-up interval of 40.8 months (range, 3-155 months), the RRU rate was 9.9% (11 of 111 patients). Positive/suspicious UCy results were noted in 12 of 111 patients, 9 of whom had RRU. A diagnosis of AUC was made in 8.6% of samples from 29 patients (41 of 477 samples). The sensitivity, specificity, positive predictive value, and negative predictive value of UCy for RRU were 82%, 97%, 75%, and 98%, respectively. Six of the 28 patients with diagnoses of AUC (21.4%) were eventually diagnosed with RRU. CONCLUSIONS In the current series, UCy demonstrated good sensitivity and high specificity for the detection of disease recurrence of UCa after RC-UD. Cancer Cytopathol 2016;124:273–8. © 2015 American Cancer Society.

&&Please give academic titles (Prof./Dr.) for each author&& Recent reports have emphasized the need for faster heterogeneous electron transfer (HET) rates of graphene electrodes in sensing and in energy-storage and -conversion applications. 2] An important consideration in this respect is the anisotropic behavior of HET. The basal plane (BP) is inferior to edge planes (EPs) by 1–7 orders of magnitude both on graphene and crystalline graphites (Figure 1). 4] Another consideration is that exposure of the BP to electrolyte solution is the natural configuration for graphene and graphite electrodes. Various methods have been developed to improve HET kinetics and performance at graphene electrodes. These methods include laser-scribing, ion irradiation, heteroatom doping, and various functionalizations. 2,5, 6, 7] Many of these strategies appear to increase the edge exposure and/or the structural disorder within the BP of graphene and graphite electrodes. Increasing disorder increases the density of states (DOS) near the Fermi level of these zero band-gap semiconductors. 4,8, 9, 10] Ideally, any technique aimed at increasing HET kinetics should focus on

There is limited data regarding hyperbaric oxygen's effectiveness in the treatment of nonhealing arterial insufficiency ulcers. This study was designed to analyze healing rates and amputation rates in patients who underwent adjunctive hyperbaric oxygen for a nonhealing arterial insufficiency ulcer. A retrospective chart review was completed on patients who underwent hyperbaric oxygen for arterial insufficiency ulcers that failed to heal despite standard treatment. Information collected included complete ulcer healing, amputation, and patient characteristics. There were 82 patients identified. A majority did not have diabetes (84.1%). The overall rate of healing was 43.9%. The overall major amputation rate was 17.1%. The amputation rate among those who healed was 0% compared to 42.4% among those not healed (p

Urinary tract cytology has a long history of utilization for the diagnosis and follow-up of tumors involving the urothelial tract. As expected, the most common tumor encountered in exfoliative urine cytology is urothelial carcinoma. While the sensitivity of urinary tract cytology for the diagnosis of low-grade urothelial carcinomas is low, its sensitivity and accuracy for high grade urothelial carcinomas is much higher. However, nonurothelial malignancies, such as hematopoietic malignancies, can also be encountered in urine specimens. Leukemic cells in urine can be diagnosed readily by cytological examination in cases where more invasive procedures are difficult to perform. Additionally, cell block sections can be utilized to determine the immunocytochemical profile of the tumor cells to confirm the diagnosis. Herein we report a case of a 75-year-old man with a past medical history of acute myeloid leukemia (AML), who presented with congested heart failure and painless macroscopic hematuria. AML relapse was diagnosed. Cytological examination of the urine using a ThinPrep® smear, cytospin preparation, and immunohistochemical stains performed on the cell block sections were examined. Findings were consistent with leukemic cells of myeloid origin in the bladder washing specimen.

The walls of angiogenic blood vessel capillaries are composed of two principal cell types, blood vessel endothelial cells (BEC) and pericytes (PC), whereas the walls of lymphatic capillaries are composed of lymphatic endothelial cells (LEC). In this investigation we describe a practical application of NIH ImageJ software for quantitative image analysis for pericytes and endothelial cells in prostate cancer. We used a tissue microarray that contained 49 tissue cores (normal prostate tissue or prostatic carcinomas with Gleason scores of 6 through 10). These prostate cancer samples represented AJCC prognostic stages II, III, and IV. Slides were immunostained with anti-PDGFR-β antibody for identification of PC, and quantified as microvascular pericyte density (MVPD); they were also immunostained with anti-CD34 antibody for identification of LEC and BEC simultaneously, and quantified as microvascular endothelial density (MVED). CD31 and D2-40 immunostains were used to quantify BEC and lymphatic endothelial cells, respectively. Our results showed higher MVPD and MVED in prostate cancers with higher Gleason scores and higher stages, suggesting the prognostic utility of vascular image analysis in prostate pathology. This investigation demonstrates the feasibility, versatility, and ease of use of ImageJ software and pericyte-specific and endothelial-specific immunohistochemistry for quantitative image analysis in prostate pathology.

BACKGROUND In urine cytology, the diagnosis of atypia is subjective and clinical management based on these results can be difficult to determine. In this study, the authors determined the percentage of atypical urine diagnoses that progressed to positive cytology or surgical pathology results over an 11-year period. METHODS In a retrospective review of the authors’ institution, 1320 atypical urine cytology diagnoses were identified in specimens from 851 patients obtained from January 2000 through December 2010. All subsequent pathology reports were reviewed to determine which patients developed positive cytology/surgical pathology diagnoses. In total, 4106 cytology and surgical pathology specimen reports were reviewed. RESULTS At the authors’ institution, 1320 of 16,299 of urine cytology specimens (8.1%) were diagnosed as atypical during the 11-year period. Overall, 271 of 1320 initial atypical urine specimens (21%) progressed to positive cytology or surgical pathology results with a mean time to progression of 155 days. Of the cases that progressed to malignancy, 118 were high-grade urothelial carcinoma and 92 were low-grade urothelial carcinoma. CONCLUSIONS The rate of atypia in urine specimens at this institution was 8.1%. Of the specimen types, atypia was the most common in urinary diversion specimens (16%) and the least common in upper tract cytology (3.8%). When diagnosed as atypical, upper tract specimens had the highest percentage of progression to high-grade carcinoma. Therefore, the authors concluded that the diagnosis of atypia in this specimen group has higher clinical significance and should be managed more aggressively. Cancer (Cancer Cytopathol) 2013;121:387–391. © 2013 American Cancer Society.

BACKGROUND Patients with low-grade urothelial carcinoma (LGUC) are at risk of recurrence and must undergo lifelong surveillance. To date, cytology and cystoscopy are the gold standard for the detection of de novo and recurrent LGUC. The objective of the current study was is to further characterize the role of cytology and cystoscopy in determining the risk of recurrence and progression in these patients. METHODS The authors retrospectively identified patients with LGUC who had urine cytology within 2 months of biopsy, and data were abstracted from their electronic charts. Electronic medical records were reviewed for cystoscopic findings and histologic and cytologic follow-up data over a 5-year period. Statistical analysis was performed with chi-square tests. RESULTS In total, 76 patients were identified who had histologic follow-up material available, and 49% of those patients demonstrated progression or recurrence of urothelial carcinoma. The initial presence of multiple lesions on cystoscopy was associated with any recurrence or progression (67.7% vs 31%; P = .002), tumor size >2 cm was associated with initial positive or suspicious urine cytology (23.8% vs 3.7%; P = .076), and positive or suspicious initial cytology was associated with high-grade recurrence (58.3% vs 19.4%; P = .009). CONCLUSIONS Cystoscopic findings, such as the presence of multiple lesions, together with concurrent positive or suspicious urine cytology, were associated with recurrence or progression of LGUC. These findings may help to identify high-risk patients. Cancer (Cancer Cytopathol) 2012;121:398–402. © 2012 American Cancer Society.

Memory is essential for our normal daily lives and our sense of self. Ca2+ influx through the NMDA-type glutamate receptor (NMDAR) and the ensuing activation of the Ca2+ and calmodulin-dependent protein kinase (CaMKII) are required for memory formation and its physiological correlate, long-term potentiation (LTP). The Ca2+ influx induces CaMKII binding to the NMDAR to strategically recruit CaMKII to synapses that are undergoing potentiation. We generated mice with two point mutations that impair CaMKII binding to the NMDAR GluN2B subunit. Ca2+-triggered postsynaptic accumulation is largely abrogated for CaMKII and destabilized for TARPs, which anchor AMPA-type glutamate receptors (AMPAR). LTP is reduced by 50% and phosphorylation of the AMPAR GluA1 subunit by CaMKII, which enhances AMPAR conductance, impaired. The mutant mice learn the Morris water maze (MWM) as well as WT but show deficiency in recall during the period of early memory consolidation. Accordingly, the activity-driven interaction of CaMKII with the NMDAR is important for recall of MWM memory as early as 24 h, but not 1–2 h, after training potentially due to impaired consolidation.

Urothelial carcinoma (UC) is the most common malignant neoplasm of the urinary tract. Metastases of UC are most common in the regional lymph nodes, lungs, liver, bone, and adrenal glands. Fine-needle aspiration cytology diagnosis of such metastases can be difficult, particularly in the setting of incomplete clinical history or when multiple primary neoplasms may be present. This review focuses on the cytologic features helpful in differentiating UC from its potential mimics, as well as ancillary studies that may be helpful in the distinction.

Three isoforms of a vesicular glutamate transporter (VGLUT1-3) have been identified. Of these, VGLUT1 is the major isoform in the cerebral cortex and hippocampus where it is selectively located on synaptic vesicles of excitatory glutamatergic terminals. Variations in VGLUT1 expression levels have a major impact on the efficacy of glutamate synaptic transmission. Given evidence linking alterations in glutamate neurotransmission to various neuropsychiatric disorders, we investigated the possible influence of a down-regulation of VGLUT1 transporter on anxiety, depressive-like behaviour and learning. The behavioural phenotype of VGLUT1-heterozygous mice (C57BL/6) was compared to wild-type (WT) littermates. Moreover, VGLUT1-3 expression, hippocampal excitatory terminal ultrastructure and neurochemical phenotype were analysed. VGLUT1-heterozygous mice displayed normal spontaneous locomotor activity, increased anxiety in the light-dark exploration test and depressive-like behaviour in the forced swimming test: no differences were shown in the elevated plus-maze model of anxiety. In the novel object recognition test, VGLUT1(+/-) mice showed normal short-term but impaired long-term memory. Spatial memory in the Morris water maze was unaffected. Western blot analysis confirmed that VGLUT1 heterozygotes expressed half the amount of transporter compared to WT. In addition, a reduction in the reserve pool of synaptic vesicles of hippocampal excitatory terminals and a 35-45% reduction in GABA in the frontal cortex and the hippocampus were observed in the mutant mice. These observations suggest that a VGLUT1-mediated presynaptic alteration of the glutamatergic synapses, in specific brain regions, leads to a behavioural phenotype resembling certain aspects of psychiatric and cognitive disorders.

OBJECTIVES To assess the early histological effects of pharmacological androgen deprivation (AD), which have been assessed only over longer periods, as surgical castration leads rapidly to diminished cell proliferation and enhanced cell death within the prostate. PATIENTS AND METHODS With Institutional Review Board approval, 35 patients were randomly assigned (seven in each group) to receive 0, 7, 14, 21 and 28 days of AD (flutamide, 250 mg orally three times/day, and one injection with leuprolide acetate 7.5 mg) before radical prostatectomy. The surgical specimens were assessed by conventional histology and immunohistochemistry, while macroarray analysis and quantitative real-time polymerase chain reaction (QRT-PCR) were used to examine gene expression. RESULTS There were morphological changes within the prostatic tissues as early as 7 days after initiating AD, similar to the response to castration. There was tumour cell vacuolization indicating cellular injury, glandular atrophy and mononuclear cell infiltration as prominent and progressive effects but, by contrast with castration studies, there were no changes in epithelial proliferation or apoptosis. Macroarray analysis, validated by QRT-PCR and immunohistochemistry, showed up-regulation of numerous and potentially counter-effective genes involved in the cell cycle and apoptosis. CONCLUSIONS Pharmacological AD induces significant involution within prostatic tissues over 7-28 days, but allows the persistence of some viable tumour cells capable of proliferation.

The significance of making a diagnosis of follicular neoplasm on fine needle aspiration (FNA) biopsy remains a controversial issue, considering that the diagnosis of follicular carcinoma is based on histological criteria and the significantly decreasing incidence of follicular carcinoma in the general population. On FNA the main differential diagnoses of follicular neoplasm includes follicular variant of papillary carcinoma (FVPC), follicular adenoma, follicular carcinoma and benign solitary nodule occurring in a goiter. Several studies have looked at immunohistochemical and molecular markers to distinguish benign from malignant lesions but none of them have proved to be infallible. Although, FVPC is a distinct entity from the follicular neoplasm group, it is not always possible to separate it from the other follicular lesions because of overlapping cytologic features and often-sporadic presence of nuclear features, follicular variant of papillary carcinoma remains the main pitfall in a diagnosis of follicular neoplasm. Since a significant number of cases that are malignant on follow-up are usually FVPC, consequently, follicular neoplasm is an essential diagnostic consideration on FNA. In addition, follicular carcinoma, despite a decreasing incidence continues to be a real entity. Therefore, it is essential that follicular neoplasm continue to be part of our diagnostic repertoire.

BACKGROUND Prostate needle biopsy (PNB) ploidy status has proven utility to predict adverse outcomes after prostatectomy. We sought to develop models to predict ploidy status using clinicopathologic variables. METHODS We identified a cohort of 169 patients with a diagnosis of prostatic adenocarcinoma on PNB, and estimated ploidy status (determined using Feulgen stained biopsy tissue) using four predictors, including age, prebiopsy PSA, highest Gleason score (GS), and the percentage of involvement by carcinoma at the biopsy site with the highest GS (PCARBX). Logistic regression (LR), Neural Network (NN), and CART classifiers were constructed. RESULTS Univariate analyses revealed all four predictors to be significantly associated with ploidy status. On multivariable analyses, LR identified a 2-parameter model, including GS and PCARBX that had a significant ability to predict ploidy status with a 74% and 75% correct classification rate (CCR), respectively. Using the same variables, CART and NN yielded similar CCRs of 70.4%. Within GS = 6 cohort, the CART model classified over 90% of biopsies as diploid when patients had a PCARBX

Vesicular glutamate transporters (VGLUTs) are essential to glutamatergic synapses and determine the glutamatergic phenotype of neurones. The three known VGLUT isoforms display nearly identical uptake characteristics, but the associated expression domains in the adult rodent brain are largely segregated. Indeed, indirect evidence obtained in young VGLUT1-deficient mice indicated that in cells that co-express VGLUT1 and VGLUT2, the transporters may be targeted to different synaptic vesicles, which may populate different types of synapses formed by the same neurone. Direct evidence for a systematic segregation of VGLUT1 and VGLUT2 to distinct synapses and vesicles is lacking, and the mechanisms that may convey this segregation are not known. We show here that VGLUT1 and VGLUT2 are co-localized in many layers of the young hippocampus. Strikingly, VGLUT2 co-localizes with VGLUT1 in the mossy fibers at early stages. Furthermore, we show that a fraction of VGLUT1 and VGLUT2 is carried by the same vesicles at these stages. Hence, hippocampal neurones co-expressing VGLUT1 and VGLUT2 do not appear to sort them to separate vesicle pools. As the number of transporter molecules per vesicle affects quantal size, the developmental window where VGLUT1 and VGLUT2 are co-expressed may allow for greater plasticity in the control of quantal release.

Papillary renal cell carcinoma is a rare type of renal malignancy. Cytogenetic findings characteristic for this tumor have been described as well as mutations of the proto-oncogene c-met. Secondary malignancies occurring together with papillary renal cell carcinomas are rare, and are often of genitourinary tract origin. We describe two cases of papillary renal cell carcinoma occurring in association with two other visceral malignancies, gastrointestinal stromal tumor and colon adenocarcinoma.Two cases of papillary renal cell carcinoma diagnosed by fine-needle aspiration (FNA), occurring in association with gastrointestinal malignancies were reviewed. Both aspirates showed cytologic features characteristic for papillary renal cell carcinoma, namely papillary structures, foamy histiocytes, intracytoplasmic hemosiderin, and nuclear grooves. Subsequent histology and immunohistochemical stains supported the cytologic diagnosis. The histologic diagnosis of gastrointestinal stromal tumor and colon adenocarcinoma were confirmed. Papillary renal cell carcinoma is a type of renal carcinoma that can be often accurately diagnosed by FNA. The occurrence of associated visceral malignancies has never been reported. The possible role of the protooncogene c-met in the development of these tumors was explored.

To determine the effect of stereotactic core-needle biopsy (SCNB) on the utilization of breast fine-needle aspirate (FNA) biopsy, we retrospectively reviewed 1,568 cases of breast FNAs that were obtained from 1,188 patients between the years 1990 and 2000. There were 378 positive and atypical cases and 497 negative and unsatisfactory cases in the pre-SCNB group (between 1990 and 1996; 7 years); and 225 positive and atypical cases and 468 negative and unsatisfactory cases in the post-SCNB group (between 1997 and 2000; 4 years). The average number of cases per year in the pre- and post-SCNB groups was 125 and 173, respectively. While the average positive/atypical cases per year in both groups remained relatively constant, the average negative/unsatisfactory cases per year were significantly increased in the post-SCNB group (117 in the post-SCNB vs. 71 in the pre-SCNB). The increase in this group was due to a true increase in the negative diagnoses, since unsatisfactory rate decreased in the post-SCNB group (12.6% in the post-SCNB vs. 9.3% in the pre-SCNB). The sensitivity, specificity, positive predictive value, and negative predictive value were 90%, 79%, 92%, and 82% in the pre-SCNB group and 93%, 86%, 91%, and 90% for the post-SCNB group, respectively. In conclusion, the implementation of SCNB did not result in a decrease in the total number of breast FNAs; however, the distribution of cases changed. FNA is increasingly used to complete the triple test in clinically and radiographically negative cases. Diagn. Cytopathol. 2004;31:106–110. © 2004 Wiley-Liss, Inc.

The diagnosis of atypia in breast fine-needle aspiration (FNA) continues to be an area of debate in cytology practice. The aim of this study was to assess the clinical significance of this term and to evaluate potential morphological criteria, which would determine the patient's outcome. A computer-based search was carried out to retrieve breast FNAs performed between 1990 and 2000 that were diagnosed as atypical. Cases followed by surgical resection were reexamined for the presence of morphological features potentially differentiating benign and malignant lesions. Out of 1,568 breast FNAs, there were 64 cases (4%) with a diagnosis of atypia. Thirty-eight cases had surgical follow-up material that revealed malignancy in 14 cases (37%) and benign lesions in 24 cases (63%). The benign diagnostic categories included fibrocystic change (12/24), fibroadenoma (3/24), tubular adenoma (2/24), and nonspecific findings (7/24). The malignant diagnoses included ductal carcinoma (9/14), lobular carcinoma (3/14), ductal carcinoma in situ (DCIS; 1/14), and tubular carcinoma (1/14). The evaluation of cytological criteria used to differentiate benign from malignant lesions (i.e., cellularity, loss of cohesion, myoepithelial cells, nuclear enlargement, nuclear overlap, prominent nucleoli) revealed significant overlap between benign and malignant cases, particularly in cases of fibroadenoma, tubular adenoma, and proliferative breast disease. The surgical follow-up of four hypocellular cases revealed lobular carcinoma in two cases and ductal carcinoma in the remaining two cases. Our study confirmed that the diagnosis of atypia is clinically significant because it is associated with a high probability of malignancy. No morphological criterion is able to reliably differentiate benign and malignant lesions in cases diagnosed with atypia. Diagnosis of atypia is particularly significant in hypocellular cases. We recommended that breast FNAs with a diagnosis of atypia be evaluated further histologically.

Background Recruiting workers in small construction companies and securing their participation in voluntary safety programs or safety research poses unique challenges. Worker turnover and worksite changes contribute to difficulties in locating and enrolling participants. Economic pressures and time demands potentially threaten ongoing participation. Methods Six simulation exercises designed to reduce back and fall injuries in small construction companies were developed based on data from focus groups of workers and company owners. Working with a workers' compensation insurer, we had access to owner-operators of general, heavy, and special trade construction companies reporting less than $10,000 in payroll expenses. Recruitment methods included a participation incentive, mailed invitations followed by phone contacts, and follow-up reminders. Results Despite using recruitment methods recommended in the literature, participation rates were low over a 2-year intervention period. Because of these difficulties, factors affecting participation or nonparticipation became an additional research focus. Owners' perceptions of already having a good safety record and of the time demands of participation were the most commonly cited reasons for not participating. Conclusions Literature on recruitment emphasizes processes and procedures under investigator control rather than understanding potential participants' judgments about the adequacy of their existing practices and the potential benefits of intervention participation relative to potential time and productivity trade-offs. Greater attention to such judgments may enhance recruitment and participation in under-studied and difficult to access populations. Am. J. Ind. Med. 45:297–304, 2004. © 2004 Wiley-Liss, Inc.

Objective To determine the effect of repeated and prolonged vaginal distension on the leak-point pressure (LPP) and urethral anatomy in the female rat, as prolonged vaginal distension has been clinically correlated with signs of stress urinary incontinence (SUI). Materials and methods Sixty female rats were placed into one of five groups; four groups underwent one of four vaginal distension protocols using a modified 10 F Foley catheter, i.e. prolonged (1 h), brief (0.5 h), intermittent (cycling inflated/deflated for 0.5 h) or sham distension. All animals had a suprapubic bladder catheter implanted 2 days after and were assessed urodynamically 4 days after vaginal distension. The fifth group of rats acted as controls and did not undergo vaginal distension, but did have a suprapubic bladder catheter placed and urodynamics assessed. To measure LPP the rats were anaesthetized with urethane, placed supine and the bladder filled with saline (5 mL/h) while bladder pressure was measured via the bladder catheter. LPPs were measured three times in each animal by manually increasing the abdominal pressure until leakage at the urethral meatus, when the external abdominal pressure was rapidly released. Peak bladder pressure was taken as the LPP and a mean value calculated for each animal. Immediately after measuring LPP the urethra was removed and processed routinely for histology (5 µm sections, stained with haematoxylin/eosin and trichrome). The means ( sem ) were compared using a Kruskal–Wallis one-way anova on ranks, followed by a Dunn's test, with P

Fibromas are rare, benign intrascrotal tumors. There are only a handful of case reports that specifically discuss these masses. 1-5 Here we present a case of fibroma of the testicular tunics and its imaging characteristics. The radiologic appearance of these tumors is variable; our goal is to familiarize the radiologist with the imaging characteristics of this clinical entity.

The laser scanning cytometer (LSC) is a relatively new instrument that combines the features of both flow and static image cytometry. The purpose of this study was to examine the application of the LSC for evaluation of DNA ploidy in routine cytologic specimens. The material for this study consisted of 60 routine cytologic specimens obtained from 33 males and 27 females ranging in age from 23–87 yr (mean, 58 yr). The specimens were simultaneously stained with propidium iodide and FITC-cytokeratin, either on Thin-Prep slide (35 cases) or in a concentrated cell suspension (25 cases). In each case a minimum of 500 cells was evaluated (range, 527–17,963; mean, 3,889). All abnormal cell populations were relocated for the presence of malignant cells. The results were defined as diploid and aneuploid/tetraploid. In 10 bladder washes, the results of LSC were compared to results of flow cytometry. Out of 60 specimens, 7 (11%: 6 bladder washes and 1 renal wash) were excluded due to low cellularity. Of the remaining 53 cases, 11 (20%) were aneuploid/tetraploid, and 42 (80%) were diploid. All but one cytologically diagnosed malignancy had abnormal DNA content. Additionally, two bladder washes diagnosed as suspicious and atypical were aneuploid. All abnormal LSC results were confirmed by relocation of the cells. The concordance between flow cytometry and LSC in the 10 control bladder washes was 100%. In conclusion, LSC proved to be a suitable instrument for the evaluation of DNA ploidy in routine cytologic specimens. Diagn. Cytopathol. 2001;24:200–205. © 2001 Wiley-Liss, Inc.

DNA analysis is becoming an important diagnostic and prognostic adjunct test in urinary cytology. The aim of this study was to compare the results of DNA flow cytometry (FCM) with the cytologic diagnosis of bladder washings (BW). DNA ploidy was evaluated in 251 BW. In 65 cases, follow-up surgical biopsies were available. Cytology results were classified as positive and negative, and FCM results were categorized as diploid and aneuploid. Both tests were evaluated independently. Cases were defined as discordant if the cytology was negative and FCM was aneuploid, or if the cytology was positive and FCM was diploid. All discordant cases were reviewed, and positive predictive values (PPV) for FCM and cytology were calculated for cases with follow-up biopsy results. Cytologic evaluation classified 181 cases as negative, with 175 of them diploid and 6 aneuploid; and 70 as positive, with 53 of them diploid and 17 aneuploid. Overall, there were 59 discordant cases (23.5%, with a confidence limit of 18.2–28.8%). Of 6 aneuploid/cytology-negative cases, biopsies were available in 4 cases and showed one grade 1, two grade 2, and one grade 3 urothelial carcinoma (UC). Reanalysis of these 6 cytology specimens showed 1 case that should have been interpreted as positive (false negative), 4 true negatives, and 1 polyoma virus infection. Out of 53 diploid/cytology-positive cases, biopsies were available in 45 cases and showed nine grade 1, 14 grade 2, three grade 3 UCs, 11 UCs in situ, and eight negative biopsies. The PPV for cytology was 85%, and the PPV for FCM was 95%. We concluded that FCM, which requires a large number of cells, often cannot detect small aneuploid populations, which are present particularly in cases of UC in situ. Diagn. Cytopathol. 2000;22:65–69. © 2000 Wiley-Liss, Inc.

The ThinPrep Pap Testtrade mark is a fluid-based method used for the collection and preparation of cervicovaginal samples. The collection device(s) is/are rinsed in Cytyc's ThinPrep PreservCyt medium and a thin-layer slide is prepared using the ThinPrep 2000 automated processor. The purpose of this study was to determine the detection rates for cervical lesions utilizing an additional ThinPrep slide. Fifty-four cervical samples processed by the ThinPrep method were reviewed. An additional thin-layer slide was obtained from the cellular residue for each case utilizing a new filter. Case selection criteria included cases with a few equivocal cells, a few diagnostic cells, or several low-grade dysplastic cells seen on the original ThinPrep slide. The original slides and repeat slides were reviewed by two cytopathologists and two cytopathology fellows. Fifty-four patients were included in the study, mean age 35 years (range: 16-76). The original diagnoses included: 17 negative cases, 22 atypical squamous cells of undetermined significance (ASCUS), 10 low-grade squamous intraepithelial lesions (LGSILs), four high-grade squamous intraepithelial lesions (HGSILs), and one case of atypical glandular cells of undetermined significance (AGUS). On the repeat slides the diagnosis remained the same in 42 (77.8%) cases, diagnostic cells were not present in 10 (18.5%) cases, fungal elements consistent with candida were detected on the repeat smear in one case (1.8%), and higher grade dysplastic cells were found in two cases (3.7%). Our study showed that the ThinPrep method provides a representative, diagnostic sample on the slide. Repeat processing adds little to the overall diagnosis.

Fine-needle aspiration (FNA) of the thyroid gland is a widely utilized, sensitive, specific, and cost-effective method for the evaluation of thyroid nodules. The purpose of this study was to evaluate the accuracy of thyroid FNA and causes of cytohistological discordance in our institution. Six hundred twenty-five thyroid FNAs obtained from 503 females (mean age, 54) and 122 males (mean age, 51) in whom histopathologic follow-up material was available for review, were analyzed. FNAs were classified as: nondiagnostic, negative, intermediate, and positive for malignancy, and the histopathologic material was categorized as benign or malignant. The review revealed 93% sensitivity and 96% specificity for the FNA diagnoses. The FNA results were diagnostic in 87%, indeterminate in 6%, and nondiagnostic in 7% of the cases. Cytohistologic correlation was achieved in 88% of the cases. The false-negative rate was 4% and the false-positive rate was 8%. The most common pitfalls for false-negative diagnoses consisted of suboptimal material and underdiagnosis of papillary carcinoma due to cystic degeneration. The most common pitfall for false-positive cases was overdiagnosis of follicular neoplasms. Our study confirmed that FNA of thyroid nodules can be performed with high sensitivity and specificity by experienced clinicians or pathologists. The application of strict specimen adequacy rules for FNA interpretation is likely to decrease the rate of false-negative and false-positive diagnoses.

Inflammatory pseudotumor, fibrohistiocytic type, also called benign fibrous histiocytoma, is a rare reactive entity usually found incidentally on routine chest roentgenography. We present a case of inflammatory pseudotumor, fibrohistiocytic type, initially diagnosed by fine-needle aspiration (FNA) cytology in a 39-yr-old woman with a history of breast carcinoma. Cytomorphologic characteristics were confirmed by a cell block examination and immunohistochemical findings. The differential diagnoses of the fine-needle aspiration cytology of this type of inflammatory pseudotumor are discussed.

Concomitant lymphoma and metastatic carcinoma are an unusual occurrence in a lymph node. We report two patients in whom synchronous malignancies were diagnosed by fine-needle aspiration biopsy (FNAB). In one case, the FNAB diagnoses of both small lymphocytic lymphoma and metastatic breast carcinoma were the initial diagnoses. In the second case, metastatic poorly differentiated squamous carcinoma was an unexpected finding in a patient with a history of small lymphocytic lymphoma. The aspirates in both cases showed two distinct cell populations, one consisting of a dispersed population of small uniform lymphoid cells and the other comprising large atypical single cells and cohesive clusters of epithelial cells. In both cases, the cytologic diagnoses were supported by immunohistochemical and flow cytometric studies.

Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. This study evaluates the cytomorphologic features of endometriosis in various cytologic specimen types [fine-needle aspiration (FNA), effusion cytology (EF), touch imprint (ToP), and cervical smear (PAP)], and assesses the key elements helpful in recognizing this lesion. A total of 18 cases (8 FNA, 4 EF, 5 ToP, and 1 PAP) of cytologically diagnosed and histologically/clinically confirmed endometriosis diagnosed between 1988 and 2006 comprises the material for this study. The morphologic features evaluated of the three components included: cellularity, presence of sheets of glandular cells, three-dimensional (3D) glandular clusters, tubular structures, single cells, syncytial groups of stromal cells, stromal cells entrapped within basement membrane (BM)-like material, cytologic atypia, presence of mitotic figures, and hemosiderin-laden histiocytes. Endometrial glands, stroma, and hemosiderin-laden histiocytes were all identified in 14/18 (77.8%) cases. FNA specimens were more cellular than that of both EF and ToP specimens. Tubular structures, 3D glandular clusters, stromal cells entrapped in BM and syncytial stromal groups were more common in FNAs, and ToPs compared with the EFs. The ratio of the endometrial glandular and stromal cells was similar in all specimen types. Atypia and mitotic figures were rarely encountered. Diagnosis of endometriosis could be made independently on either smears/ThinPrep(™) slides or on cell blocks in all cases where these preparations were available. On follow up, none of the patients developed malignancy. Endometriosis can be reliably and safely diagnosed in various cytologic materials. Cytologic atypia is uncommon. Components of endometriosis could show minor morphologic alterations in different specimen types.

We report the cytologic features of eight fine-needle aspirations (FNA) and eight exfoliative specimens of collecting duct carcinoma (CDC) obtained from six patients. The four men and two women ranged in age from 27 to 69 years (mean = 45 yr) and all had advanced stage disease at presentation (one stage III, five stage IV). Five of the six patients died of widespread disease, and one is alive and well (mean survival, 28 mo ; range, 11-48 mo). The smears of the FNA and exfoliative specimens were scantly to moderately cellular. Tumor cells showed moderate pleomorphism and were arranged primarily in cohesive groups that rarely had a papillary configuration. Nuclei had irregular nuclear contours, coarse chromatin, and one to three nucleoli. In the majority of cases the cytoplasm was finely vacuolated, and occasionally there were large intracytoplasmic vacuoles. Intracytoplasmic mucin was demonstrated in two aspirates. Psammoma bodies were present in four of the seven fluids. In two patients, the cytologic diagnosis was supported by positive immunostaining for high-molecular-weight keratin and Ulex europaeus agglutinin I lectin. Leu M-1 was focally positive in one case and negative in the other. The cytologic features of CDC were readily identified as malignant ; however, they were not distinctive and overlapped with those of high-grade renal cell carcinoma with papillary features and transitional cell carcinoma.

A Sertoli-Leydig-cell tumor is an exceptionally rare neoplasm. We present the pelvic washing cytomorphology of an ovarian Sertoli-Leydig-cell tumor with a retiform pattern in a 24-yr-old female. The cytologic features in this case were tight tissue fragments composed of small, relatively uniform cells with scanty cytoplasm and small rounded or blunt papillary fragments with hyalinized cores lined with small, mildly atypical cuboidal cells. Differential diagnoses included borderline and well-differentiated papillary serous tumors, clear-cell carcinoma, and collagen balls. Correlation of cytologic findings with histomorphology is crucial for correct interpretation of pelvic washings in cases of Sertoli-Leydig-cell tumors.

Patients with rheumatoid arthritis may develop extra-articular subcutaneous nodules as part of the systemic disease or as initial manifestation. These lesions may represent significant diagnostic dilemmas in patients with clinical suspicion of malignancy. In this setting, fine-needle aspiration (FNA) of the nodules may be the simplest and most appropriate diagnostic approach. In the literature, however, there are only sporadic reports describing FNA cytology of a rheumatoid nodule. In this report, we present a case of a 67-year-old male with a history of rheumatoid arthritis and squamous-cell carcinoma of the larynx who developed a subcutaneous neck nodule in the immediate proximity of the surgical scar. Clinically, because of the history of squamous-cell carcinoma and location of the lesion, the nodule was suspected to be metastatic cancer, but was proven by FNA biopsy to represent rheumatoid disease. Cytological criteria of rheumatoid nodule and diagnostic difficulties are discussed.

The purpose of this study was to evaluate the efficacy of routine use of ThinPrep® in fine-needle aspiration (FNA) material as an adjunct to standard smears. We reviewed 50 consecutive, satisfactory-for-evaluation FNA materials in which ThinPrep® slides were obtained. In each case, Diff-Quik-stained and Papanicolaou-stained smears were initially prepared, and the ThinPrep® slide was made from the needle/syringe rinse. Smears and ThinPrep® slides were evaluated for the presence of diagnostic material. In addition, the following questions were addressed: could the final diagnosis be made based on smears only, and did the ThinPrep® method add any additional information to the diagnosis? Smears were satisfactory for evaluation in 49/50 cases, and in one case diagnostic material was present on the ThinPrep® slide only. Thirty-two out of 50 ThinPrep® slides contained material sufficient for evaluation. In 46/50 (92%) cases, final diagnoses could be made based on smears only. In 2 cases, ThinPrep® slides showed additional diagnostic material, and in another 2 cases were critical for the diagnosis. The routine use of ThinPrep® as an adjunct preparatory method to FNA material is not justified, and is associated with an additional, potentially nonreimbursable cost. Diagn. Cytopathol. 2001;25:101–103. © 2001 Wiley-Liss, Inc.

A retrospective 7 1/4-yr study was performed to evaluate the diagnostic accuracy of fine-needle aspiration (FNA) cytology in the cell typing of persistent or recurrent gynecologic malignancies. A total of 202 aspirates were obtained from 163 patients with documented malignancies of the cervix, uterus, ovary, vulva, and vagina. Information concerning the primary tumor was obtained from surgical reports and/or medical records. In 168/202 cases (83%), the histological diagnosis, including primary tumor cell type and subtype (ex. squamous cell carcinoma, large cell keratinizing), were available. In 12/202 cases (6%), only the tumor cell type (ex. squamous cell carcinoma) was known, and in the remaining 22 cases (11%), only the location of the primary neoplasm was attainable. Aspirated sites included pelvic wall and organs (77 cases), lymph nodes (51 cases), thoracic organs (18 cases), and abdominal wall and organs (56 cases), including liver (33 cases). Of the 168 cases with known histologic diagnoses, the FNA results were positive in 109 (65%). The positive results were divided into three groups: group I, the cytologic findings were predictive of the histologic diagnoses (84 cases, 77%); group II, tumor cell subtyping was not possible on cytology (17 cases, 16%); group III, neither tumor cell typing nor subtyping was possible on cytology (8 cases, 7%). Of the 34 cases in which only the histologic tumor cell type or primary tumor location was known, 13 (38%) were positive on FNA.(ABSTRACT TRUNCATED AT 250 WORDS)