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27 years of experience
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Education ?

Medical School Score
Drexel University (1983)
  • Currently 2 of 4 apples

Awards & Distinctions ?

American Board of Pathology

Affiliations ?

Dr. Young is affiliated with 8 hospitals.

Hospital Affilations



  • Montgomery Hospital XXXXX
    900 E Fornance St, Norristown, PA 19401
    • Currently 3 of 4 crosses
    Top 50%
  • Albert Einstein Medical Center
    5501 Old York Rd, Philadelphia, PA 19141
    • Currently 3 of 4 crosses
    Top 50%
  • Hahnemann University Hospital
    230 N Broad St, Philadelphia, PA 19102
    • Currently 2 of 4 crosses
  • American Oncologic Hospital TA Fox Chase Cancer Center
  • Elkins Park Hospital
    60 Township Line Rd, Elkins Park, PA 19027
  • Germantown Hospital & Community Health Services
    1 Penn Blvd, Philadelphia, PA 19144
  • Mossrehab & Albert Einstein Med Ctr
    60 Township Line Rd, Elkins Park, PA 19027
  • Fox Chase Cancer Center
    333 Cottman Ave, Philadelphia, PA 19111
  • Publications & Research

    Dr. Young has contributed to 51 publications.
    Title Role of Cytology in the Management of Non-small-cell Lung Cancer.
    Date October 2011
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Title Seizures, but Not Lowered Seizure Thresholds, Results in Larger Neocortical Motor Maps and Concomitant Disruptions in Skilled Motor Behaviour.
    Date November 2010
    Journal Behavioural Brain Research

    Kindling of the sensorimotor neocortex has been found to result in reorganization of the somatotopic map of movement representations as well as disruptions of skilled forelimb behaviours. It has been suggested that the repeated seizures induced during kindling altered motor maps, thereby disrupting the motor engram necessary for the production of skilled movements. However, kindling leads to neural changes other than those associated with repeated seizures, and the role of these comorbid effects is often overlooked. Our lab has developed a stimulation paradigm, which allows for the dissociation of the two main effects of kindling; repeated seizures and the reduction of afterdischarge (seizure) threshold. In the current study, we have utilized this paradigm to examine the effects of electrical stimulation on motor maps and skilled forelimb behaviour. We found that repeated seizures with no concomitant reduction of afterdischarge threshold resulted in large motor maps, as well as task specific deficits in skilled forelimb use and deficiencies in task acquisition. Rats that had reduced seizure thresholds and few seizures did not show alterations in map size or skilled forelimb use. These results suggest that movement disturbances following kindling are the result of repeated seizures, and not other stimulation-induced effects such as reduction of afterdischarge threshold. These results also corroborate the relationship between the integrity of movement representations and the ability to perform skilled motor tasks.

    Title Motor Map Expansion in the Pilocarpine Model of Temporal Lobe Epilepsy is Dependent on Seizure Severity and Rat Strain.
    Date July 2009
    Journal Experimental Neurology

    Functional alterations in movement representations (motor maps) have been observed in some people with epilepsy and, under experimental control, electrically-kindled seizures in rats also result in persistently larger motor maps. To determine if a single event of status epilepticus and its latent consequences can affect motor map expression, we assessed forelimb motor maps in rats using the pilocarpine model of temporal lobe epilepsy. We examined both pilocarpine-induced seizures, and status epilepticus (SE) in two strains that differ in their propensity for epileptogenesis; Wistar and Long-Evans. Pilocarpine was administered intraperitoneally at dosages that resulted in equivalent proportions of seizures, SE, and survival in both strains. Rats from both strains were given saline injections as a control. Diazepam was administered to all rats to attenuate seizure activity and promote survival. All rats had high-resolution movement representations derived using standard intracortical microstimulation methodologies at 48 h, 1 week, or 3 weeks following treatment. Pilocarpine-induced seizures only gave rise to motor map enlargement in Wistar rats, which also showed interictal spiking, and only at 3 weeks post-treatment indicating altered motor map expression in this strain following a latent or maturational period. Pilocarpine-induced SE yielded larger motor maps at all time points in Wistar rats but only a transient (48 h) map expansion in Long-Evans rats. Our results demonstrate that seizures and SE induced by a convulsant agent alter the functional expression of motor maps that is dependent on seizure severity and a genetic (strain) predisposition to develop epileptiform events.

    Title Proteomic Analyses of Pancreatic Cyst Fluids.
    Date April 2009
    Journal Pancreas

    There are currently no diagnostic indicators that are consistently reliable, obtainable, and conclusive for diagnosing and risk-stratifying pancreatic cysts. Proteomic analyses were performed to explore pancreatic cyst fluids to yield effective diagnostic biomarkers.

    Title Motor Maps, Seizures, and Behaviour.
    Date August 2008
    Journal Canadian Journal of Experimental Psychology = Revue Canadienne De Psychologie Expérimentale

    Atypically organised motor maps have been described in some people with epilepsy and we have modelled this in rats. Our goal is to more fully understand the mechanisms responsible for seizure-induced functional brain reorganisation and to reverse their effects. Here we present an overview of the relationship between neocortical motor maps, seizures, and interictal behaviour. To begin we summarise the observations of atypical motor maps with epilepsy and in animal models following experimentally induced seizures. Our novel experiments have established that motor map expansion is linked to a functional alteration of motor behaviour. Evidence for some of the putative brain mechanisms responsible for motor map size is discussed. Our successes reversing seizure-induced map expansion by two different methods are also briefly reviewed. Lastly, unanswered questions for possible future experimentation are posed.

    Title The Declining Pap Test: an Omen of Extinction or an Opportunity for Reform?
    Date July 2008
    Journal Acta Cytologica
    Title General Method of Preparation of Mesoporous M/si3n4 Nano-composites Via a Non-aqueous Sol-gel Route.
    Date July 2007
    Journal Chemical Communications (cambridge, England)

    We report a general method for the preparation of transition-metal silicon nitride nanocomposites; for example, mesoporous Pd-Si3N4 nanocomposite materials with high surface area were prepared by pyrolysis of a silicon palladium imide-chloride complex which was synthesized by reaction of silicon diimide gel with palladium chloride. These porous nanocomposites catalyse organic reactions.

    Title Induction of Neocortical Long-term Depression Results in Smaller Movement Representations, Fewer Excitatory Perforated Synapses, and More Inhibitory Synapses.
    Date February 2007
    Journal Cerebral Cortex (new York, N.y. : 1991)

    Long-term depression (LTD) is one of the most widely investigated models of the synaptic mechanisms underlying learning and memory. Previous research has shown that induction of LTD in the neocortex decreases measures of pyramidal cell dendritic morphology in both layers III and V. Here, we investigated the effects of LTD induction on 1) the time course of recovery of synaptic efficacy, 2) movement representations, 3) cortical thickness and layer V neuron density, and 4) the density of excitatory and inhibitory synapses in layer V of sensorimotor neocortex. Rats carried a stimulating electrode in the midline corpus callosum and a recording electrode in the right sensorimotor neocortex. Each rat received either low-frequency stimulation composed of 900 pulses at 1 Hz or handling daily for a total of 20-25 days. Callosal-neocortical evoked potentials were recorded in the right hemisphere before and after stimulation or handling. Our results show that LTD induction lasts for 3 weeks and results in smaller motor maps of the caudal forelimb area. We did not observe any reduction in neocortical thickness or neuron density. There was a reduction in the density of excitatory perforated synapses and an increase in the density of inhibitory synapses in layer V of the sensorimotor neocortex, thereby providing a general mechanism for the reduction in motor map size. This study sheds light on the interaction between an artificial model of learning, receptive field characteristics, and synaptic number in the sensorimotor cortex.

    Title Fine-needle Aspiration Biopsy of Lymphoproliferative Disorders--interpretations Based on Morphologic Criteria Alone: Results from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.
    Date December 2006
    Journal Archives of Pathology & Laboratory Medicine

    CONTEXT: Diagnosis of lymphoproliferative disorders is one of the most challenging tasks faced by the cytologist. The initial cytomorphologic evaluation of lymphoproliferative lesions directs the choice of ancillary studies that ultimately lead to a diagnosis based on the World Health Organization classification system using a composite of clinical, morphologic, immunophenotypic, and molecular features. OBJECTIVE: To evaluate the ability of participating laboratories in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology to appropriately categorize lymphoproliferative lesions based solely on cytomorphologic criteria. DESIGN: Laboratory responses for lymph node aspirates were examined. All responses were based on review of glass slides without ancillary immunologic or molecular data available. The benchmarking data provided for each specific diagnosis were analyzed, with a focus on the performance for evaluation of lymphoproliferative lesions. RESULTS: Based on morphology alone, responses for lymph node aspirates in the Non-Gynecologic Cytopathology program were correct to the exact reference diagnosis for 87.1% of Hodgkin lymphoma. Non-Hodgkin lymphoma was identified in 69.5% of the large cell non-Hodgkin lymphoma cases, of which 66.8% were correctly classified as large cell type. Non-Hodgkin lymphoma was identified in 68.1% of non-Hodgkin lymphoma, other than large cell cases, and of these, 94.7% were identified as other than large cell type. CONCLUSIONS: The spectrum of specific responses was consistent for lymphoproliferative lesions, with a reasonable differential diagnosis based on cytomorphology alone, which, in practice, facilitates the appropriate choice of immunophenotypic markers and other ancillary studies.

    Title The Potential for Failure in Gynecologic Regulatory Proficiency Testing with Current Slide Validation Criteria: Results from the College of American Pathologists Interlaboratory Comparison in Gynecologic Cytology Program.
    Date August 2006
    Journal Archives of Pathology & Laboratory Medicine

    CONTEXT: Current regulatory proficiency testing scoring results in an automatic failure for identifying high-grade squamous intraepithelial lesion (HSIL) as negative. OBJECTIVE: The College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology data from January 2004 to April 2005 were analyzed to estimate the percentage of failure based on negative responses for HSIL and validation criteria. DESIGN: More than 15,000 participants received field-validated and educational slide sets for conventional, ThinPrep, and SurePath modules. Educational sets fulfilled the validation criteria of the Center for Medicare and Medicaid Services, which required the consensus diagnosis of biopsy-proven HSIL (not field-validated) after review by 3 pathologists. The College of American Pathologists field validation required at least 20 responses to the HSIL+ series, with 70% matched to HSIL+ (standard error < or = 0.05). Minimum regulatory proficiency testing failure estimates were based on incorrect negative responses for the reference category of HSIL. RESULTS: For both cytotechnologists and pathologists, there was a statistically significant higher failure rate for slides that were not field-validated versus those that were field-validated. In conventional modules, 5.3% of the slides that were not field-validated were called negative, versus 1.2% of the field-validated slides. In all liquid-based preparations, 4.0% of the non-field-validated versus 2.2% field-validated slides were called negative. Pathologists would have failed more often than cytotechnologists for the slides that were not field-validated, whereas there was no statistical difference in failure performance with field-validated slides. CONCLUSIONS: Failures were significantly greater with the slides that were not field-validated for both conventional and liquid-based preparations (ThinPrep only) and have implications for both regulatory proficiency testing and expert legal review. Poor performance of pathologists relative to that of cytotechnologists may reflect a lack of prescreening of slides or scope of practice issues.

    Title Radiofrequency Ablation of Primary Lung Cancer: Results from an Ablate and Resect Pilot Study.
    Date December 2005
    Journal Chest

    STUDY OBJECTIVES: The role of radiofrequency ablation (RFA) for primary lung cancer remains poorly defined. The purpose of this "ablate and resect" pilot study was to evaluate the safety of performing RFA in patients with primary non-small cell lung cancer (NSCLC) and to characterize the histologic changes in tumor tissue following such ablation. DESIGN: This prospective study was undertaken at a single institution, and 10 patients were accrued from June 2002 to June 2003. Eligible patients included those with clinical stage I or II disease. RFA of the tumor was performed through a standard thoracotomy followed by conventional lobectomy and lymph node dissection. Extent of cell death was determined histologically. MEASUREMENTS AND RESULTS: Following the exclusion of two patients, the treated portions of eight tumors were examined for tumor cell viability. Gross inspection and routine histologic staining could not reliably identify the "immediately ablated" tissue. However, using a supravital staining technique, the treated areas from seven of the eight tumors (87.5%) demonstrated > 80% nonviability (100% nonviability was noted in the treated areas from three of the eight tumors). No bleeding or thermal complications were noted at the time of RFA, and none of the patients had skin burns at the electrode dispersive pad sites. CONCLUSIONS: RFA of primary NSCLC is feasible and can be performed safely in the setting of an open thoracotomy. Complete tumor cell necrosis, as determined by supravital staining, was noted in the treated areas from three of eight tumors (37.5%). Such complete ablation was observed in the treated areas from smaller tumors (< 2 cm), whereas the treated areas from larger tumors demonstrated incomplete ablation. Additional investigation with histopathologic correlation is needed to fully assess the long-term efficacy of RFA for NSCLC.

    Title Fine-needle Aspiration of Pulmonary Hamartoma: a Common Source of False-positive Diagnoses in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.
    Date June 2005
    Journal Archives of Pathology & Laboratory Medicine

    CONTEXT: We use data from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology to evaluate the accuracy of fine-needle aspiration (FNA) biopsy for diagnosing pulmonary hamartoma (PH). OBJECTIVE: To use the performance characteristics of the PH cases in the Nongynecologic Cytology Program to determine the accuracy of FNA for identifying these lesions and to determine potential sources of interpretative errors. DESIGN: A retrospective review of the College of American Pathologists Nongynecologic Cytology cumulative data from 1997 to 2003 was performed to identify the overall accuracy of FNA for diagnosing PH and to determine the most common interpretative pitfalls. The slides from each of the cases of PH in the Nongynecologic Cytology Program were then reviewed in an effort to identify the cytologic characteristics that contributed to the poor performance of these cases. RESULTS: A total of 766 participant responses for 19 PH FNA specimens were reviewed. The specificity of FNA for making the correct general reference interpretation of benign was 78%. The false-positive rate was 22%, with the most common false-positive diagnoses being carcinoid tumor, adenocarcinoma, and small cell carcinoma. The overall accuracy for making the correct specific reference diagnosis of PH was 26%. Microscopic review of the individual cases revealed possible explanations for some of the interpretative errors and the most frequent false-positive interpretations. CONCLUSIONS: Cytologists should be aware of the potential false-positive interpretations that can occur in FNAs of PH and the potential reasons for these inaccuracies in order to minimize clinically significant diagnostic errors.

    Title Soft X-ray Photochemistry at the L2,3-edges in K3[fe(cn)6], [co(acac)3] and [cp2fe][bf4].
    Date May 2005
    Journal Journal of Synchrotron Radiation
    Title Cytologic Features of High-grade Squamous Intraepithelial Lesion in Thinprep Papanicolaou Test Slides: Comparison of Cases That Performed Poorly with Those That Performed Well in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.
    Date November 2004
    Journal Archives of Pathology & Laboratory Medicine

    CONTEXT: Conventional Papanicolaou (Pap) test slides of high-grade squamous intraepithelial lesions (HSILs) that are frequently misdiagnosed are known to have relatively few dysplastic cells. Whether this is true of cases of HSIL in ThinPrep Pap Test specimens is not known. OBJECTIVE: To determine if cases of HSIL in ThinPrep specimens that are frequently missed have relatively few dysplastic cells. DESIGN: The cytologic features of 16 ThinPrep cases of HSIL that performed poorly in the College of American Pathologists Interlaboratory Comparison Program were compared with 22 ThinPrep Pap Test cases that performed extremely well. RESULTS: Significantly more cases that performed poorly had fewer than 250 dysplastic cells (13/16) than cases that performed well (3/22) (P <.001). CONCLUSION: ThinPrep Pap Test cases with a diagnosis of HSIL that performed poorly in this program had significantly fewer dysplastic cells than those that performed well.

    Title Structural Study of the Thermal and Photochemical Spin States in the Spin Crossover Complex [fe(phen)2(ncse)2].
    Date October 2004
    Journal Chemistry (weinheim an Der Bergstrasse, Germany)

    The first structural data for [Fe(phen)(2)(NCSe)(2)] (obtained using the extraction method of sample preparation) in its high-spin, low-spin and LIESST induced metastable high-spin states have been recorded using synchrotron radiation single crystal diffraction. The space group for all of the spin states was found to be Pbcn. On cooling from the high-spin state (HS-1) at 292 K through the spin crossover at about 235 K to the low-spin state at 100 K (LS-1) the iron coordination environment changed to a more regular octahedral geometry and the Fe-N bond lengths decreased by 0.216 and 0.196 A (Fe-N(phen)) and 0.147 A (Fe-N(CSe)). When the low-spin state was illuminated with visible light at about 26 K, the structure of this LIESST induced metastable high-spin state (HS-2) was very similar to that of HS-1 with regards to the Fe-phen bond lengths, but there were some differences in the bond lengths in the Fe-NCSe unit between HS-1 and HS-2. When HS-2 was warmed in the dark to 50 K, the resultant low-spin state (LS-2) had an essentially identical structure to LS-1. In all spin states, all of the shortest intermolecular contacts (in terms of van der Waals radii) involved the NCSe ligand, which may be important in describing the cooperativity in the solid state. The quality of the samples was confirmed by magnetic susceptibility and IR measurements.

    Title Grading Follicular Lymphoma. The Achilles Heel of Diagnosis by Cytology.
    Date May 2004
    Journal Acta Cytologica
    Title The Four R's: Reactive/repair, Reporting, and Regulations.
    Date February 2004
    Journal Diagnostic Cytopathology
    Title Cortical Stimulation Improves Skilled Forelimb Use Following a Focal Ischemic Infarct in the Rat.
    Date January 2004
    Journal Neurological Research

    Improving functional recovery following cerebral strokes in humans will likely involve augmenting brain plasticity. This study examined skilled forelimb behavior, neocortical evoked potentials, and movement thresholds to assess cortical electrical stimulation concurrent with rehabilitative forelimb usage following a focal ischemic insult. Adult rats were trained on a task that required skilled usage of both forelimbs. They then underwent an acute focal ischemic insult to the caudal forelimb area of sensorimotor cortex contralateral to their preferred forelimb. During the same procedure, they also received a stimulation electrode over the infarct area and two depth electrodes anterior to the lesion to record evoked potentials. One week following the surgery, rats received cortical stimulation during performance of the skilled task. Evoked potentials and movement thresholds were also determined. Functional assessment revealed that cortical stimulation resulted in superior performance compared to the no stimulation group, and this was initially due to a shift in forelimb preference. Cortical stimulation also resulted in enhanced evoked potentials and a reduction in the amount of current required to elicit a movement, in a stimulation frequency dependent manner. This study suggests that cortical stimulation, concurrent with rehabilitative training, results in better forelimb usage that may be due to augmented synaptic plasticity.

    Title Comparison of Performance of Conventional and Thinprep Gynecologic Preparations in the College of American Pathologists Gynecologic Cytology Program.
    Date January 2004
    Journal Archives of Pathology & Laboratory Medicine

    CONTEXT: Results of clinical trials suggest that interpretation of liquid-based cytology preparations is more accurate and is associated with less screening error than interpretation of conventional preparations. OBJECTIVE: In this study, the performance of participants in interpreting ThinPrep (TP) preparations was compared with participants' performance on conventional Papanicolaou tests in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP). DESIGN: The results of the PAP from the year 2002 were reviewed, and the discordancies to series and exact-match error rates for the 2 cytologic methods were compared. RESULTS: For this study, a total of 89 815 interpretations from conventional smears and 20 886 interpretations from TP samples were analyzed. Overall, interpretations of TP preparations had both significantly fewer false-positive (1.6%) and false-negative (1.3%) rates than those of conventional smears (P =.001 and P =.02, respectively) for validated or validated-equivalent slides, as assessed by concordance with the correct diagnostic series. In this assessment of concordance to series, interpretations of educational TP and conventional preparations were similar, except for high-grade squamous intraepithelial lesion, in which the performance was significantly worse for educational TP preparations (false-negative rate of 8.1% vs 4.1% for conventional smears, P <.001). When interpretations were matched to the exact diagnosis, validated-equivalent TP preparations were generally more accurate for diagnoses in the 100 series and 200 series than were conventional smears. Notably, for the reference diagnosis of squamous cell carcinoma, the exact-match error rate on validated equivalent TP slides was significantly greater than that of conventional slides (44.5% vs 23.1%, P <.001). Interpretations of educational TP preparations also had a significantly higher error rate in matching to the exact reference diagnosis for squamous cell carcinoma (33.7% vs 22.8%, P =.007). CONCLUSIONS: Overall, TP preparations in this program were associated with significantly lower error rates than conventional smears for both validated and educational cases. However, unlike the negative for intraepithelial lesion and malignancy, not otherwise specified, low-grade squamous intraepithelial lesion, and adenocarcinoma cytodiagnostic challenges, participants' responses indicated some difficulty in recognizing high-grade squamous intraepithelial lesion and squamous cell carcinoma.

    Title Kindling-induced Emotional Behavior in Male and Female Rats.
    Date August 2003
    Journal Behavioral Neuroscience

    Modeling fear in animals is a critical approach for identifying the neural mechanisms involved in human disorders such as generalized anxiety and panic. Amygdala kindling has proven useful in this regard because it produces dramatic increases in fearful behavior. The purpose of this experiment was to compare the behavioral effects of kindling in male and female rats. Compared with the sham-stimulated rats, the kindled male and female rats showed similar increases in fearful behavior, with some sex differences in fear-related open-field activity. They also showed decreased immobility in the forced-swim test and increased sucrose consumption. These results suggest that kindling-induced fear is generally similar in male and female rats and that kindling does not appear to induce depression-like behavior.

    Title Cytologic Approach to Tumors of the Tracheobronchial Tree.
    Date April 2003
    Journal Chest Surgery Clinics of North America

    Cytologic testing is an integral part of the workup of patients suspected of having lung cancer. These tests are less invasive than other tissue procurement methods, with minimal risk of complications. In experienced hands, the tests are highly accurate and reliable. To achieve good results and avoid diagnostic errors, clinicians must be educated in proper collection and fixation methods and the pathologist should be cognizant of clinical and radiologic data. Close communication between the clinician and pathologist should be encouraged.

    Title The Clinical Utility of the Das-1 Monoclonal Antibody in Identifying Adenocarcinoma of the Colon Metastatic to the Liver in Fine-needle Aspiration Tissue.
    Date February 2003
    Journal Cancer

    BACKGROUND: The cytologic diagnosis of adenocarcinoma in a liver mass usually is straightforward. Identifying where the adenocarcinoma arose from is much more problematic. The Das-1 immunostain is directed against a colon specific antigen and has shown excellent sensitivity and specificity for adenocarcinoma of the colon in surgical pathology studies. In the current study, the authors examined the clinical utility of the Das-1 immunostain in the setting of fine-needle aspiration cell block material from the liver. METHODS: The cell block material from 77 fine-needle aspiration biopsy specimens from the liver were studied. These included 17 hepatocellular carcinomas, 20 colon adenocarcinomas that were metastatic to the liver, and 40 other malignancies, predominantly adenocarcinomas, that were metastatic to the liver from a variety of primary tumor sites. Each case was stained with the Das-1 immunostain using the avidin-biotin complex method and evaluated in a blinded fashion for membranous and/or cytoplasmic staining. The diagnoses were unblinded and correlated with staining and clinical history. RESULTS: Thirteen of 20 metastatic colon carcinoma samples exhibited immunostaining whereas only 2 of the remaining 57 samples of malignancy exhibited immunostaining. CONCLUSIONS: The results of the current study suggest that the Das-1 immunostain may prove to be helpful in identifying adenocarcinomas in the liver as arising from the colon.

    Title Diagnosis and Subclassification of Breast Carcinoma by Fine-needle Aspiration Biopsy: Results of the Interlaboratory Comparison Program in Non-gynecologic Cytopathology.
    Date January 2003
    Journal Archives of Pathology & Laboratory Medicine

    CONTEXT: The College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology is a popular educational program for nongynecologic cytology that had 1018 participating laboratories by the end of 2000. Data generated from this program allow for tracking performance on slides in a diverse group of laboratories. OBJECTIVE: We reviewed the performance of participating laboratories on fine-needle aspiration biopsies of the breast with particular interest in the ability of participants to accurately subclassify breast carcinoma. DESIGN: We reviewed the responses of participating laboratories for glass slides of breast fine-needle aspiration biopsies for the year 2000. We analyzed benchmarking data provided for each specific diagnosis. RESULTS: The overall false-negative rate for laboratories was 6.2%, and the overall false-positive rate was 1.1%. Most of the breast carcinomas were correctly identified as malignant on the general diagnosis, but participants had more difficulty subclassifying types of breast carcinoma. The rate of correct exact diagnosis was 65% for ductal adenocarcinoma, 20% for lobular adenocarcinoma, 12% for medullary carcinoma, and 27% for mucinous carcinoma. CONCLUSIONS: This study shows that fine-needle aspiration biopsy of the breast is a reliable method for the diagnosis of breast carcinoma, but difficulties still exist in our ability to determine tumor subtype.

    Title Clinical Significance of Performing Immunohistochemistry on Cases with a Previous Diagnosis of Cancer Coming to a National Comprehensive Cancer Center for Treatment or Second Opinion.
    Date September 2002
    Journal The American Journal of Surgical Pathology

    Immunohistochemistry (IHC) is an important adjunctive test in diagnostic surgical pathology. We studied the clinical significance and outcomes in performing IHC on cases with a previous diagnosis of cancer who are coming to the Fox Chase Cancer Center (FCCC), a National Cancer Institute designated National Comprehensive Cancer Center (NCCC), for treatment and/or second opinion. We reviewed all the outside surgical pathology slide review cases seen at the FCCC for 1998 and 1999 in which IHC was performed. Cases were divided into the following: confirmation of outside diagnoses without and with prior IHC performed by the outside institution (groups A and B, respectively) and cases with a significant change in diagnosis without and with prior IHC performed by the outside institution (groups C and D, respectively). During 1998 and 1999, 6678 slide review cases were reviewed at the FCCC with an overall significant change in diagnosis in 213 cases (3.2%). IHC was performed on 186 of 6678 (2.7%) slide review cases with confirmation of the outside diagnosis in 152 (81.7%) cases and a significant change in diagnosis in 34 (18.3%) cases. Patient follow-up was obtained in 32 of 34 (94.1%) cases with a significant change in diagnosis (groups C and D), which confirmed the correctness of our diagnosis in 26 of 27 cases (96%; in five cases follow-up was inconclusive). We repeated the identical antibodies performed by the outside institutions in group D (37 antibodies) and group B (133 antibodies) with different results in 48.6% and 13.5%, respectively (overall nonconcordance 21.2%). In group D additional antibody tests beyond that performed by the outside institution were needed in 88.8% of cases to make a change of diagnosis. In the setting of a NCCC, reperforming and/or performing IHC on cases with a previous diagnosis of cancer is not a duplication of effort or misuse of resources. Repeating and/or performing IHC in this setting is important in the care and management of patients with cancer.

    Title Misinterpretation of Normal Cellular Elements in Fine-needle Aspiration Biopsy Specimens: Observations from the College of American Pathologists Interlaboratory Comparison Program in Non-gynecologic Cytopathology.
    Date July 2002
    Journal Archives of Pathology & Laboratory Medicine

    CONTEXT: The College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology is a popular educational program for nongynecologic cytology, with 1018 participating laboratories by the end of 2000. Data generated from this program allow tracking pathologist performance in a wide variety of laboratory practices. OBJECTIVE: To review performance of participating pathologists in making patient diagnoses with fine-needle aspiration biopsy specimens, with particular interest in the false neoplastic diagnoses (both benign and malignant neoplasms) that were submitted for benign aspirates containing only normal cellular components. DESIGN: We reviewed the diagnoses made from 1998 through 2000 by participating pathologists through the use of glass slides containing benign fine-needle aspiration biopsy specimens of the liver, kidney, pancreas, and salivary gland that contained only normal cellular components. RESULTS: The false neoplastic rate for kidney (60%) was the highest, followed by liver (37%), pancreas (10%), and salivary gland (6%). These rates are much higher than what has previously been reported in the literature. CONCLUSIONS: This study illustrates that normal cellular elements are a significant pitfall for overinterpretation of fine-needle aspiration biopsy specimens.

    Title Diagnostic Utility of Glut-1 and Ca 15-3 in Discriminating Adenocarcinoma from Hepatocellular Carcinoma in Liver Tumors Biopsied by Fine-needle Aspiration.
    Date March 2002
    Journal Cancer

    BACKGROUND: Diagnosing liver tumors can be difficult in the setting of a poorly differentiated tumor or tumors with no known prior malignancy. Frequently, alpha-fetoprotein, carcinoembryonic antigen, factor VIII, and mucicarmine have been employed to distinguish hepatocellular carcinoma (HCC) from adenocarcinoma. However, these stains have their limitations. CA 15-3 and Glut-1 are expressed in a variety of carcinomas. To the authors' knowledge, their expression in HCC has not been studied extensively. The authors examined the clinical utility of CA 15-3 and Glut-1 in the setting of fine-needle aspiration biopsy samples from the liver. METHODS: Thirty-five cases of HCC and 59 cases of tumors metastatic to the liver were studied. These cases previously were studied with the hepatocyte paraffin-1 antibody. Each case was stained with CA 15-3 and Glut-1 using the avidin-biotin complex method. Each case was evaluated in a blinded fashion for membranous staining that was stronger than cytoplasmic or background staining. The diagnoses were unblinded and staining patterns were compared. RESULTS: CA 15-3 stained 43 of 59 metastatic carcinoma samples and 3 of 35 HCC samples. Glut-1 stained 34 of 59 metastases and 2 of 35 HCCs. Together, the 2 immunostains stained 51 of 59 metastases and 5 of 35 HCCs. Diagnostic accuracy was improved by adding hepatocyte paraffin-1 to the staining panel. CONCLUSIONS: CA 15-3 and Glut-1, especially in conjunction with hepatocyte paraffin-1, appear to be helpful in discriminating HCC from other carcinomas.

    Title Diagnostic Value of Hepatocyte Paraffin 1 Antibody to Discriminate Hepatocellular Carcinoma from Metastatic Carcinoma in Fine-needle Aspiration Biopsies of the Liver.
    Date August 2001
    Journal Cancer

    BACKGROUND: Diagnosing liver tumors by fine-needle aspiration biopsy is safe and accurate. However, there are cases that prove diagnostically difficult. Traditionally, immunostains for alpha-fetoprotein and polyclonal carcinoembryonic antigen have been used to distinguish adenocarcinomas from hepatocellular carcinomas (HCCs). In poorly differentiated tumors, these immunostains have limitations in both sensitivity and specificity. An hepatocyte-specific immunostain has been described in the surgical pathology literature. To the authors' knowledge, this hepatocyte antibody has not been studied in liver fine-needle aspiration biopsies. The authors examined the Hepatocyte Paraffin 1 (HP1) antibody for its diagnostic utility in this cytologic setting. METHODS: Cell-block material from 40 cases of HCC and 53 cases of metastatic adenocarcinoma were studied. Slides were stained for HP1 by the avidin-biotin complex method following antigen retrieval. The percentage of malignant cells that exhibited coarse granular staining in the cytoplasm was estimated for all cases of HCC, poorly differentiated HCC, and metastatic adenocarcinoma. RESULTS: HP1 was expressed in 83% of all HCCs but in only 56% of poorly differentiated HCCs. Only 2 of 53 (4%) of metastatic tumors expressed HP1. The overall sensitivity of HP1 was 79% and its specificity was 96%. CONCLUSION: HP1 was found to be a specific immunostain that may prove helpful in diagnosing all but the most undifferentiated liver tumors biopsied by fine-needle aspiration.

    Title Differentiating Large Cell Lymphoma from Indolent Small B-cell Lymphoma in Fine Needle Aspirates Using P53, Pcna and Transformed Lymphocyte Count.
    Date August 2000
    Journal Acta Cytologica

    OBJECTIVE: To determine the usefulness of proliferating cell nuclear antigen (PCNA), p53 protein expression and transformed lymphocyte count (TLC) as adjunctive tests to differentiate indolent small B-cell lymphoma from large cell lymphoma in fine needle aspiration biopsies. STUDY DESIGN: Aspirates of lymphoproliferative disorders from April 1993 to January 1997 were reviewed. The percentage of TLCs was determined on the Papanicolaou smear. The percentage and intensity of p53 and PCNA immunocytochemical staining was evaluated on cell block sections. These results were compared and correlated with the final diagnoses based on available morphology, flow cytometry and clinical history. RESULTS: There were 40 cases of non-Hodgkin's lymphoma and 12 reactive lymph nodes. Adequate cell blocks were available on 16 large cell lymphomas, 7 grade 1-2 follicular center cell lymphomas, 6 mucosal associated lymphoid tissue lymphomas, 2 small lymphocytic lymphomas and 2 mantle cell lymphomas. Average TLC and p53 nuclear staining was highest in large cell lymphomas (57% TLC and 24% p53), followed by grades 1 and 2 follicular lymphomas (14% TLC and 15% p53) and lowest in other indolent lymphomas (< 10% TLC and < 1% p53). Average PCNA staining was highest in large cell lymphomas (46%) and lowest in small lymphocytic lymphomas (7%); however, TLC was the best parameter for differentiating large cell lymphoma from indolent small B-cell lymphoma. CONCLUSION: TLC differentiated large cell lymphoma from indolent small B-cell lymphoma better than either p53 or PCNA alone or in combination. Significant overlap between categories limits usefulness of these immunocytochemical stains for differentiating these entities.

    Title Preoperative Chemotherapy of Chemoradiotherapy for the Treatment of Adenocarcinoma of the Pancreas and Ampulla of Vater.
    Date January 1999
    Journal Journal of Hepato-biliary-pancreatic Surgery

    Much has been written about preoperative strategies in the treatment of pancreatic adenocarcinoma, yet there has been very little comment concerning other periampullary malignancies. This review discusses current issues relevant to the further development of preoperative adjuvant treatment of pancreatic adenocarcinoma. A small series of patients with ampullary adenocarcinomas treated with preoperative adjuvant chemoradiotherapy is also described.

    Title Utilization of Fine-needle Aspiration Cytology and Flow Cytometry in the Diagnosis and Subclassification of Primary and Recurrent Lymphoma.
    Date September 1998
    Journal Cancer

    BACKGROUND: The primary diagnosis of non-Hodgkin's lymphoma/leukemia (NHL) by fine-needle aspiration (FNA) is controversial. The authors reviewed their experience with FNA and flow cytometry (FC) to determine the usefulness and limitations of these techniques in the diagnosis of NHL. METHODS: Slides and reports from all lymph node and extranodal FNAs performed during the period July 1993 to January 1997 with a diagnosis of lymphoma or benign lymphoid process were reviewed. Clinical and biopsy follow-up data were recorded. Results were tabulated and the usefulness of cytology was analyzed. RESULTS: There were 100 adequate aspirates from 87 patients. These included 72 cases of NHL, 58 (80%) of which were diagnosed by FNA and FC without the need for histologic sampling (69% of the primary lymphomas and 88% of the recurrent lymphomas). There were 22 aspirates suspicious for lymphoma, 12 equivocal results, and 7 benign diagnoses. Eighty-six percent of malignant FNAs (50 of 58) had flow cytometry (FC) as compared with only 15% (5 of 34) of the suspicious or equivocal FNAs. CONCLUSIONS: FNA is a valuable method for diagnosing and subclassifying NHL, although immunophenotyping by FC is often an essential ancillary test. In our experience, correlating the FNA results with the FC results can eliminate the need for a more invasive surgical biopsy in many cases.

    Title The Value of Transformed Lymphocyte Count in Subclassification of Non-hodgkin's Lymphoma by Fine-needle Aspiration.
    Date September 1997
    Journal American Journal of Clinical Pathology

    No established criteria exist for predicting lymphoma grade or transformation in cytologic material. We counted transformed lymphocytes in fine-needle aspiration (FNA) biopsy specimens to determine whether the percentage of these cells in the smear could predict the histologic grade, the biologic behavior, or both. The percentage of transformed lymphocytes out of total lymphoid cells was determined on Papanicolaou-stained smears. Afterward, a cytodiagnosis was based on clinical information available at the time of the FNA, cytomorphologic data, and flow cytometry data. Results were correlated with results of examination of the surgical biopsy specimen, clinical behavior of the lymphoma, or both. The percentage of transformed lymphocytes was 10% or less in all low-grade or indolent lymphomas. Aspirates with transformed lymphocyte counts of 20% or greater were aggressive lymphomas. We also report our experience in the diagnosis of non-Hodgkin's lymphoma by FNA using cytomorphologic examination and immunophenotyping by flow cytometry at a cancer referral hospital. This is a preliminary study, and larger series may help establish the ranges of transformed lymphocyte counts that correlate with the lymphoma subtype.

    Title Interobserver Variability of Cervical Smears with Squamous-cell Abnormalities: a Philadelphia Study.
    Date April 1995
    Journal Diagnostic Cytopathology

    The reproducibility of reporting squamous lesions by the Bethesda System (TBS) was evaluated by distributing 20 slides to be classified among 5 panelists considered experts in the field of cytopathology. Four cases were chosen for their classic morphology and the remainder were foreseen to produce possible discrepancies within one diagnostic category. For 7/20 (35%) cases there was unanimous agreement. Participants disagreed within one category of magnitude for seven (35%) cases. In six (30%) cases there was a range of more than one category disagreement. However, additional written comments modifying TBS diagnoses often diminished the clinical significance of these discrepancies. We conclude that despite the important role of TBS in standardization of Pap smear reports, a great degree of subjectivity exists in classifying squamous abnormalities without "classic" morphology. The lack of reproducibility should be taken into account in cytology proficiency testing.

    Title Zinc Co-ordination in the Dna-binding Domain of the Yeast Transcriptional Activator Ppr1.
    Date March 1995
    Journal Febs Letters

    The structure of the native zinc form of the DNA binding domain in the yeast transcriptional activator PPR1 was investigated by extended X-ray absorption fine structure (EXAFS). By carrying out the EXAFS measurements at 11k we were able to demonstrate explicitly the proximity of the two zinc ions (Zn-Zn distance = 3.16 +/- 0.03 A) and the presence of bridging cysteine ligands. The results show that the six cysteine residues co-ordinate two zinc ions in a two-metal ion cluster. PPR1 is the first member of this class of protein for which such information has been obtained.

    Title Three-dimensional Volumetric Ultrasound Imaging of Arterial Pathology from Two-dimensional Intravascular Ultrasound: an in Vitro Study.
    Date May 1994
    Journal Angiology

    The objectives of this study were to evaluate: (1) the feasibility of generating three-dimensional (3-D) ultrasound (US) volumetric images of arterial segments from intravascular (IV) US images by retaining full range of gray levels; (2) the feasibility of volumetric quantitation of various arterial wall pathology from the 3-D volume US images of arterial segments. IVUS provides morphologic details of arterial wall diseases. This is seen as variation in gray levels. However, when a 3-D US image is generated currently, the full range of gray levels is not utilized. This limits optimal assessment of arterial wall pathology. Sequential cross-sectional IVUS images from 11 arterial segments consisting of various pathology were obtained in vitro by calibrated withdrawal of an IVUS catheter. These images were digitized by an 8 bit digitizer to retain full 256 gray levels of brightness. 3-D volume generation was carried out using "ANALYZE" software. After the IVUS imaging, arterial segments were sectioned transversely in a 0.3-0.4 mm cross section and stained with hematoxylin, eosin and elastin. Geometrical measurements and gross morphological changes of the arterial segments were noted and correlated with the corresponding section of the image from the three-dimensional volume. Arterial wall pathology, its extent and its effect on lumen geometry were easily appreciated in multiple tomographic sections of a 3-D volume image. Similarly, arterial wall pathology was easily quantitated from 3-D volume. The above assessments were only feasible by retaining full range of gray levels in the 3-D volume image. This study indicates that (1) it is feasible to generate a 3-D US volume image by retaining full range of gray levels from IVUS images, (2) retaining full range of gray levels allows optimal assessment of arterial wall pathology and its extent in 3-D volume, and (3) IVUS allows quantitation of arterial wall pathology, and thereby one can assess the effect of intervention.

    Title Value of Repeat Cervical Smears at the Time of Colposcopic Biopsy.
    Date May 1994
    Journal Diagnostic Cytopathology

    At our institution, gynecologists perform Pap smears not only as an initial screening procedure but also at the time of colposcopy and biopsy. We compared the results of initial Papanicolaou (Pap) smears with those taken at colposcopic biopsy to determine if repeating the Pap smear at the time of colposcopy contributed to patient management. We found that repeat colposcopic smears often agreed with the referral smears and biopsies. When there was disagreement, the colposcopic smear was more often a lower grade than the referral smear and correlated best with the biopsy. Both referral and colposcopic smears underestimated the severity of cervical lesions with the same frequency. We could document only 5/414 (1.2%) colposcopic smears that contributed to patient care.

    Title Ischemic Changes in Fetal Myocardium. An Autopsy Series.
    Date April 1994
    Journal Archives of Pathology & Laboratory Medicine

    It has been assumed that fetal myocardial necrosis is an uncommon event that occurs only under unusual circumstances. We studied random heart sections on 76 fetal and perinatal autopsies from a 4-year period to determine the types and frequency of histologic abnormalities that occur in fetal myocardium. Vacuolar degeneration was extremely common (43% of stillbirths, 84% of live births) but a nonspecific finding. Ischemic changes, which are typically associated with coagulation necrosis, myofiber waviness, or contraction band necrosis, were seen in 21% of stillbirths and 32% of live births. In the majority of cases with histologic evidence of ischemic change, a combination of either contraction band necrosis, coagulation necrosis, and/or myofiber waviness was identified. Only rarely was any one of the abnormalities seen as an isolated feature. In only two autopsies were the ischemic changes identified in the initial autopsy report. We conclude that the histologic changes associated with ischemia that may represent myocardial necrosis are not uncommon and are frequently overlooked at autopsy.

    Title Diagnostic Value of Electron Microscopy on Paraffin-embedded Cytologic Material.
    Date July 1993
    Journal Diagnostic Cytopathology

    Transmission electron microscopy (TEM) is an important adjuvant to light microscopy, but is underutilized in cytopathology because of technical obstacles. One should attempt to obtain properly fixed material for TEM whenever possible. If that is not available, TEM on the cell block requires no preplanning or additional needle passes, and avoids problems of inadequate tissue for diagnosis. However, cell blocks are often not examined because of the perception that their poor ultrastructural preservation precludes their utility. We describe our experience in performing TEM on cell blocks from 15 cytologic specimens. In 13 of 15 cases, the cell block material was adequate for ultrastructural evaluation, and it clarified or extended the diagnosis in seven of these cases. TEM is a useful adjuvant technique to cytodiagnosis and can be successfully performed on cell blocks when gluteraldehyde-fixed material is not available.

    Title Left Ventricular Outflow Tract to Left Atrial Communication Due to Mitral Valve Endocarditis.
    Date June 1993
    Journal American Heart Journal
    Title An Implementation Plan for Autopsy Quality Control and Quality Assurance.
    Date June 1993
    Journal Archives of Pathology & Laboratory Medicine

    The few guidelines that exist for performing autopsy quality assurance are vague. Much has been written about the use of the autopsy to monitor clinical services, but not how to monitor the quality of the autopsy and autopsy reports. We present the comprehensive quality assurance program that has been developed and implemented at Hahnemann University Hospital, Philadelphia, Pa, for the past 2 years; this program has encompassed quality control of our diagnostic work. Key features have included in-depth peer review of completed reports, documentation of review at conferences, and careful monitoring of turnaround time. We have found that integrating quality assurance into departmental conferences is a useful supplement to in-depth peer review of randomly chosen autopsies. Our approach to quality assurance may serve as a model for other pathology departments, particularly those with pathology residency training programs.

    Title Respiratory Cytology: a Review of Non-neoplastic Mimics of Malignancy.
    Date April 1993
    Journal Diagnostic Cytopathology

    Respiratory cytology has its share of pitfalls. Some, such as vegetable cell contaminants, pose problems for only inexperienced observers, while others, such as reactive bronchoalveolar cells from pneumonia, can lead even experienced cytopathologists to make a misdiagnosis of malignancy. This review illustrates and analyzes those benign conditions or entities known to mimic malignancy in exfoliative respiratory cytology and fine-needle aspiration biopsy of the lung. Entities are grouped by the type of malignancy they mimic, and guidelines are presented for avoiding specific pitfalls.

    Title Diagnostic Correlation of Fiberoptic Bronchoscopic Biopsy and Bronchoscopic Cytology Performed Simultaneously.
    Date May 1992
    Journal Diagnostic Cytopathology

    The reliability of bronchoscopic cytology relative to biopsy is controversial. Some still consider biopsy the definitive procedure. Comparative studies are few and limited in scope. Therefore, we compared simultaneously obtained biopsies and cytologies for 224 cases. One hundred and sixty-six cases (74.6%) correlated completely. Forty-four cases (19.6%) did not correlate and cytology was diagnostic in 24 of these. Biopsy was diagnostic in sarcoidosis and vasculitis, whereas cytology only excluded the presence of neoplasm or infection. In 14 cases (5.8%), biopsy and cytology showed pathologic changes, but one or the other was more definitive. Rarely, the 2 techniques provided complementary information. A specific diagnosis was obtained more often from the combination of cytology and biopsy than from either alone. However, when biopsy is contraindicated it is reassuring that cytology usually yields the same information as biopsy, and can detect neoplastic and infectious diseases when the biopsy is non-diagnostic.

    Title Case for the Panel. Sacral Tumor with Neuroendocrine Differentiation.
    Date July 1991
    Journal Ultrastructural Pathology
    Title Differential Diagnosis of Cystic Neoplasms of the Pancreas by Fine-needle Aspiration.
    Date June 1991
    Journal Archives of Pathology & Laboratory Medicine

    Fine-needle aspiration biopsy of pancreatic lesions is becoming widespread. Pathologists need to be familiar with the cytologic features of pancreatic tumors, of which cystic neoplasms are a distinct subset. Of our 31 pancreatic aspirates diagnostic of neoplasia, six were diagnosed as cystic by radiographic imaging. These cases were compared. Similar symptoms were experienced by all of these patients, although those with malignant tumors lost the most weight. Loss of border definition, ascites, and liver metastases were the only radiologic clues to malignancy. Each entity had distinguishing cytologic features. These cases illustrate the importance of knowing the clinical, radiologic, and cytologic features of pancreatic cystic neoplasms to arrive at a preoperative diagnosis and determine proper treatment.

    Title Search for Retrovirus-like Particles in Human Breast Cancer Cells in Culture.
    Date May 1981
    Journal Cancer Research

    We have recently established four new human breast cancer cell lines that were characterized as being of human mammary origin. We examined these cell lines for particles morphologically resembling retroviruses by electron microscopy, for extracellular and intracellular particles containing high-molecular-weight RNA and RNA-directed DNA polymerase by biochemical assays, and for mouse mammary tumor virus (MMTV)-related sequences in the cell genomes by molecular hybridization. An extensive search for budding particles by thin-section electron microscopy of cells did not provide evidence for retrovirus-like particles. Similarly, 1000- to 2000-fold concentrated samples of medium harvested from 10(8) cells did not contain particles of a density of 1.14 to 1.16 g/ml containing RNA-directed DNA polymerase. Compared with DNA polymerase activity of MMTV, and taking into account the particle weight and protein content of retroviruses, we estimate that, if these cells produce retrovirus-like particles, this production would be less than 1.6 particles/cell every 24 to 72 hr. The hybridization of cell DNA with MMTV complementary DNA also did not show detectable amounts of virus-related sequences in the cell genome. Analysis of the hybridization results suggested that, if the human breast cells contained MMTV-related sequences, they must be present in less than one copy per 100 cells. Thus, we have obtained no convincing evidence for the presence of retrovirus-like particles or subviral components in these cells. It is of course possible that these cells contain virus information but at levels below the sensitivity of our assay procedures.

    Title Histoplasma Capsulatum Endocarditis.
    Date July 1980
    Journal American Heart Journal

    Endocarditis is a rare manifestation of disseminated Histoplasma capsulatum infection. A 22-year-old man presented with a seven month history of fever, weight loss, and progressive aortic insufficiency. The diagnosis of H. capsulatum was suggested by a diagnostic rise in complement fixation titers and positive echocardiographic findings. The diagnosis was confirmed prior to surgery by positive bone marrow culture. Progressive congestive heart failure necessitated replacement of the aortic valve which subsequently grew H. capsulatum. In this case, a combination of amphotericin B therapy and valve replacement was curative.

    Title Establishment and Characterization of Three New Continuous Cell Lines Derived from Human Breast Carcinomas.
    Date November 1978
    Journal Cancer Research

    Three continuous lines of mammary tumor cells (ZR-75-1, ZR-75-27, and ZR-75-30) have been established from malignant effusions of two women with breast cancer. Differentiated properties expressed by each cell line include: (a) epithelial morphology (by light and electron microscopy) resembling that of the parental tumors; (b) presence of receptors for estrogen and other steroid hormones; and (c) growth responsiveness to estrogen and/or progesterone. All three cell lines possess human karyotypes that differ from one another in modal chromosome number as well as in characteristic marker chromosomes. Two of the cultures (ZR-75-27 and ZR-75-30), although derived from the same patient, have stable differences in their karyotypes.

    Title Small Bowel Obstruction As a Complication of Disseminated Varicella-zoster Infection.
    Date May 1978
    Journal Surgery

    A 40-year-old woman with Sjögren's syndrome and mixed cryoglobulinemia, treated with corticosteroids, presented with small bowel obstruction temporally associated with cutaneous varicella-zoster (V-Z) infection. At laparotomy a portion of inflamed, necrotic small bowel was resected. Cells in the margin of the lesion exhibited characteristic intranuclear inclusion bodies. This case report emphasizes the multiple organ involvement that can occur with disseminated V-Z infection. Despite the rarity of gastrointestinal involvement, this infection must be included in the differential diagnosis of the acute abdomen in patients with cutaneous vesicles.

    Title Interferon-mediated Inhibition of Mouse Mammary Tumor Virus Expression in Cultured Cells.
    Date October 1977
    Journal Virology
    Title Heart Muscle Performance After Experimental Viral Myocarditis.
    Date April 1976
    Journal The Journal of Clinical Investigation

    As part of an inquiry into possible antecedents of idiopathic cardiomyopathy, acute experimental coxsackie virus myocarditis was studied for late structural and functional sequelae. Myocarditis was induced in 12- and 22-day-old hamsters by inoculation with coxsackie virus B3. Early viremia occurred, followed by virus replication in heart muscle. Maximum peak developed tension (Tpd) of isometrically contracting isolated heart muscle was depressed 17 and 43% in the animals inoculated at 12 days, and studied 18 and 90 days later, respectively, as compared to their uninoculated controls. In both infected groups, less muscle stretch was required to reach the length at which Tpd was produced. Animals studied 180 days after inoculation did not differ from controls. The muscles from animals inoculated at 22 days of age and studied 18 days later showed a 15% depression of Tpd compared to their controls. Glycerinated muscles from this infected group developed 50% less tension than their controls. The muscles of hamsters inoculated with virus at 22 days and studied 90 and 180 days later showed no change in Tpd. The data suggest that contractility and compliance of heart muscle are decreased 18 days after inoculation, but recover by 90 days if the animals are inoculated at age 22 days. However, if the animals are inoculated at a younger age (12 days), depression of myocardial performance persists for at least an additional 90 days. It is concluded that the inflammatory stage of experimental acute coxsackie virus B3 myocarditis in the Syrian golden hamster may be followed by residual alterations in contractile proteins and myocardial function.

    Title Depressed Myocardial Function in Subacute Experimental Viral Myocarditis.
    Date February 1976
    Journal Recent Advances in Studies on Cardiac Structure and Metabolism

    A model of experimental Coxsackie virus B3 myocarditis has been developed in the weaning Syrian golden hamster. The acute infection is characterized by extensive viral replication in the myocardium, associated with transient myocytolysis and leukocytic infiltration. At 2 weeks after inoculation, there is survival without evidence of cardiac hypertrophy or failure, and minimal residual light microscopic changes. In order to evaluate myocardial function during convalescence form this form of myocarditis, muscle mechanics were studied in left ventricular trabeculae careae in 10 infected and 7 control animals, 18 days after inoculation. Maximum developed tension of the infected animals was depressed by 25%, and there was a significant decrease in the time to peak tension. Furthermore, the infected muscles required less stretch to reach that length at which maximal developed tension was produced. These data indicate that myocardial function remains depressed during early convalescence from acute Coxsackie virus B3 myocarditis and suggest that this state is associated with decreased compliance. Studies of myocardial morphology and function at longer intervals after acute experimental viral myocarditis are indicated, to further test the hypothesis that viral myocarditis might be a precursor chronic isiopathic cardiomyopathy.

    Title Unsuspected Etiology of Lateral Neck Masses. Cat-scratch Disease.
    Date May 1972
    Journal Archives of Otolaryngology (chicago, Ill. : 1960)

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