Use of infrared thermography to delineate temperature gradients and critical isotherms during catheter ablation with normal and half normal saline: Implications for safety and efficacy.

BACKGROUND: Radiofrequency (RF) ablation with half-normal saline (HNS) has shown promise as a bail-out strategy following failed ventricular tachycardia ablation using standard approaches. OBJECTIVE: To use a novel infrared thermal imaging (ITI) model to evaluate biophysical and lesion characteristics during RF ablation using normal saline (NS) and HNS irrigation. METHODS: Left ventricular strips of myocardium were excised from fresh porcine hearts. RF ablation was performed using an open-irrigated ablation catheter (Thermocool ST/SF) with NS (n = 75) and HNS (n = 75) irrigation using different power settings (40/50 W), RF durations (30/60 s), contact force of 10-15 g, and flow rate of 15 ml/min. RF lesions were recorded using an infrared thermal camera and border zone, lethal, 100° isotherms were matched with necrotic borders after 2% triphenyltetrazolium chloride staining. Lesion dimensions and isotherms (mm2 ) were measured. RESULTS: In total, 150 lesions were delivered. HNS lesions were deeper (6.4 ± 1.1 vs. 5.7 ±0.8 mm; p = .03), and larger in volume (633 ± 153 vs. 468 ± 107 mm3 ; p = .007) than NS lesions. Steam pops (SPs) occurred during 19/75 lesions (25%) in the NS group and 32/75 lesions (43%) in the HNS group (p = .34). Lethal (57.8 ± 6.5 vs. 36.0 ± 3.9 mm2 ; p = .001) and 100°C isotherm areas (16.9 ± 6.9 vs. 3.8 ± 4.2 mm2 ; p = .003) areas were larger and were reached earlier in the HNS group. CONCLUSIONS: RFA using HNS created larger lesions than NS irrigation but led to more frequent SPs. The presence of earlier lethal isotherms and temperature rises above 100°C on ITI suggest a potentially narrower therapeutic-safety window with HNS.

T cell-mediated antitumor immune response eliminates skin tumors induced by mouse papillomavirus, MmuPV1.

Previous studies of naturally occurring mouse papillomavirus (PV) MmuPV1-induced tumors in B6.Cg-Foxn1nu/nu mice suggest that T cell deficiency is necessary and sufficient for the development of such tumors. To confirm this, MmuPV1-induced tumors were transplanted from T cell-deficient mice into immunocompetent congenic mice. Consequently, the tumors regressed and eventually disappeared. The elimination of MmuPV1-infected skin/tumors in immunocompetent mice was consistent with the induction of antitumor T cell immunity. This was confirmed by adoptive cell experiments using hyperimmune splenocytes collected from graft-recipient mice. In the present study, such splenocytes were injected into T cell-deficient mice infected with MmuPV1, and they eliminated both early-stage and fully formed tumors. We clearly show that anti-tumor T cell immunity activated during tumor regression in immunocompetent mice effectively eliminates tumors developing in T cell-deficient congenic mice. The results corroborate the notion that PV-induced tumors are strongly linked to the immune status of the host, and that PV antigens are major anti-tumor antigens. Successful anti-PV T cell responses should, therefore, lead to effective anti-tumor immune therapy in human PV-infected patients.

MmuPV1 infection and tumor development of T cell-deficient mice is prevented by passively transferred hyperimmune sera from normal congenic mice immunized with MmuPV1 virus-like particles (VLPs).

Infection by mouse papillomavirus (PV), MmuPV1, of T cell-deficient, B6.Cg-Foxn1(nu)/J nude mice revealed that four, distinct squamous papilloma phenotypes developed simultaneously after infection of experimental mice. Papillomas appeared on the muzzle, vagina, and tail at or about day 42days post-inoculation. The dorsal skin developed papillomas and hair follicle tumors (trichoblastomas) as early as 26days after infection. Passive transfer of hyperimmune sera from normal congenic mice immunized with MmuPV1 virus-like particles (VLPs) to T cell-deficient strains of mice prevented infection by virions of experimental mice. This study provides further evidence that T cell deficiency is critical for tumor formation by MmuPV1 infection.

Histopathology of Recalcitrant Maxillary Sinusitis Necessitating Endoscopic Medial Maxillectomy.

OBJECTIVES: Endoscopic medial maxillectomy (EMM) is an effective intervention for patients with recalcitrant maxillary sinusitis after previous middle meatal antrostomy. The pathophysiology of refractory maxillary sinusitis is incompletely understood. We aim to identify trends in structured histopathology (SHP) to better understand how tissue architecture changes contribute to refractory sinusitis and impaired mucociliary clearance. METHODS: All patients who underwent EMM or standard maxillary antrostomy for recalcitrant maxillary sinusitis of various forms were included. Retrospective chart review was conducted to collect information on demographics, disease characteristics, comorbid conditions, culture data, and SHP reports. Chi-squared and logistic regression analyses were performed for SHP variables. RESULTS: Forty-one patients who underwent EMM and 464 patients who underwent maxillary antrostomy were included. On average, the EMM cohort was 10 years older (60.9 years vs. 51.1 years; p = 0.001) and more often had a history of prior sinus procedures (73.2% vs. 40.9%; p < 0.001). EMM patients had higher rates of fibrosis (34.1% vs. 15.1%, p = 0.002), and this remained statistically significant when controlling for prior sinus procedures and nasal polyposis (p = 0.001). Cultures positive for pseudomonas aeruginosa (38.2% vs. 5.6%, p < 0.001) and coagulase negative staphylococcus (47.1% vs. 23.5%, p = 0.003) were more prevalent in the EMM group. CONCLUSION: Fibrosis and bacterial infections with Pseudomonas and coagulase negative Staphylococcus were more prevalent in patients requiring EMM. This may contribute to the multifactorial etiology of impaired mucociliary clearance in patients with recalcitrant maxillary sinusitis. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2646-2652, 2024.

Epidemiological and phylogenetic analysis of institutional mouse parvoviruses.

Mouse parvoviruses (MPVs) are small, single-stranded, 5 kb DNA viruses that are subclinical and endemic in many laboratory mouse colonies. MPVs cause more distinctive deleterious effects in immune-compromised or genetically-engineered mice than immuno-competent mice. At the University of Louisville (U of L), there was an unexpected increase of MPV sero-positivity for MPV infections in mouse colonies between January 2006 and February 2007, resulting in strategic husbandry changes aimed at controlling MPV spread throughout the animal facility. To investigate these MPVs, VP2 genes of seven MPVs were cloned and sequenced from eight documented incidences by PCR technology. The mutations in these VP2 genes were compared to those found at the Genbank database (NCBI; http://www.ncbi.nlm.nih.gov) and an intra-institutional phylogenetic tree for MPV infections at U of L was constructed. We discovered that the seven MPV isolates were different from those in Genbank and were not identical to each other. These MPVs were designated MPV-UL1 to 7; none of them were minute virus of mice (MVMs). Four isolates could be classified as MPV1, one was classified as MPV2, and two were defined as novel types with less than 96% and 94% homology with existing MPV types. Considering that all seven isolates had mutations in their VP2 genes and no mutations were observed in VP2 genes of MPV during a four-month time period of incubation, we concluded that all seven MPVs isolated at U of L between 2006 and 2007 probably originated from different sources. Serological survey for MPV infections verified that each MPV outbreak was controlled without further contamination within the institution.

Middle ear adenoma: Cytohistologic features and differential diagnosis.

Middle ear adenomas are rare, low grade glandular neoplasms with epithelial and neuroendocrine components and with varying patterns of differentiation. Due to the rarity of this tumor, there is a dearth of publications detailing the cytological features. We herein review our institution's pathological database for cytological material between 1992 and 2022 for MEA specimens and discuss possible differential diagnoses based on clinical, pathological, and cytologic data and material.

Histopathologic Features of Chronic Rhinosinusitis in Diabetic Patients.

OBJECTIVE: To explore how diabetes mellitus impacts chronic rhinosinusitis clinically and on structured histopathology to provide insights on new potential chronic rhinosinusitis endotypes. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic center. METHODS: A retrospective study of chronic rhinosinusitis patients who underwent functional endoscopic sinus surgery from 2015 to 2020 was performed. Structured 13-variable histopathology reports were generated from intraoperative sinonasal specimens. These variables were compared against demographic factors, comorbidities, culture data, and preoperative Lund-Mackay and SNOT-22 scores using logistic regression. RESULTS: There were 411 patients, including 52 diabetics. Diabetes was associated with higher mean body mass index (34.9 vs 29.2; p < .001), age (57.8 vs 48.0; p < .001), and Gram-negative (40.2% vs 22.7%; p < .030) and coagulase-negative Staphylococcus (49.0% vs 28.5%; p = .008) culture rates. Black (23.1% vs 18.7%) and Hispanic (23.1% vs 8.6%) races were more common with diabetes (p = .026). Gender, smoking, polyp status, and Lund-Mackay and SNOT-22 scores did not differ between groups. Diabetics had more fungal elements (13.5% vs 3.3%, p = .018); no other histopathological differences were seen. When controlling for demographic variables and comorbidities, diabetes independently predicted the presence of fungal elements (HR 4.38, p = .018). CONCLUSION: Diabetic chronic rhinosinusitis patients demonstrated increased fungal elements on structured histopathology. Other histopathological features were unaffected by diabetes. These findings may have important implications on the medical and surgical management of diabetic chronic rhinosinusitis patients in which early fungal disease assessment is paramount.

Histopathology of Allergic Fungal Rhinosinusitis Versus Chronic Rhinosinusitis with Nasal Polyps.

OBJECTIVE: Structured histopathology (SHP) is a method of analyzing sinonasal tissue to characterize endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP). Allergic fungal rhinosinusitis (AFRS) shares several features with certain endotypes of CRSwNP. Our objective was to compare the histopathology of AFRS and eosinophilic CRSwNP to further understand whether they are separate endotypes or disease entities altogether. METHODS: A retrospective review of AFRS and CRSwNP patients undergoing endoscopic sinus surgery was performed. Data were collected on demographics, comorbidities, subjective and objective severity scores, and 13-variable SHP reports. CRSwNP patients with >10 eosinophils per high-power field (eCRSwNP) were included. Chi-squared and t-tests were used for statistical analysis. RESULTS: A total of 29 AFRS and 108 eCRSwNP patients were identified. AFRS patients were younger and more often Black. Symptom severity scores (SNOT-22, Lund-MacKay, and Lund-Kennedy) were uniform between groups. AFRS patients had a higher rate of Charcot-Leyden crystals (41.4% vs. 10.2%; p < 0.001). Severe degree of inflammation, eosinophilic inflammatory predominance, eosinophil aggregates, subepithelial edema, and basement membrane thickening were common in both groups, and their rates were not statistically significantly different between groups. Metaplasia, ulceration, fibrosis, and hyperplastic/papillary change rates were low (<30%) and similar between groups. CONCLUSION: The SHP of eCRSwNP and AFRS are highly consistent, which suggests AFRS is a severe subtype of CRSwNP overall rather than a separate disease entity. This also lends credence to AFRS belonging on the endotypic spectrum of CRSwNP. LEVEL OF EVIDENCE: 3 Laryngoscope, 2023.

Molecular diagnosis of a laboratory mouse papillomavirus (MusPV).

MusPV, a novel papillomavirus (PV) that naturally infects laboratory mice, was isolated and characterized from a colony of NMRI-Foxn1(nu)/Foxn1(nu) (nude) mice in India. Because MusPV may have been missed during routine pathogen screening of mice in colonies worldwide, a variety of detection methods are described to detect MusPV. The clinical and histologic lesions of productive MusPV infections fit PV-associated features, including papillomas, koilocytes within the stratum granulosum of the hyperplastic/acanthotic papillomatous epithelium, and the presence of intranuclear virus particles in koilocytotic cells visualized by electron microscopy. Antiserum against disrupted PV virions, isolated from another species (canine), identified conserved viral antigens in productively infected cells by immunohistochemistry. A rolling circle technique was used to amplify viral circular DNAs followed by endonuclease restriction enzyme digestion to determine the correct size of PV DNA. Consensus PV degenerative primers, My09/11, commonly used to detect many different types of PVs by polymerase chain reaction (PCR), particularly mucosotropic HPVs, also identified MusPV and all rodent PVs tested. Since there was one nucleotide mismatch between the My09/11 primer set and the MusPV template, a new primer set, MusPV-My09/11, was designed to specifically detect MusPV in latent infections and spontaneous MusPV-induced papillomas. Southern blot analysis verified the presence of full size PV DNA in infected tissues. Virus-like particles (VLPs), generated from MusPV L1 genes, provided a substrate for serological testing of naturally and experimentally infected mice. In summary, a series of diagnostic assays were developed and validated to detect MusPV infection in skin tumors and serological response in laboratory mice.

Variability in Depth of Invasion Measurements in Carcinomas of the Oral Cavity and the Effect on Pathologic Tumor Staging.

Depth of invasion (DOI) was added to the staging criteria for carcinoma of the lip and oral cavity in the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC8). However, there are multiple practical challenges to obtaining an accurate DOI measurement with limited data regarding interobserver variability in DOI measurement. The aim of this study was to investigate interobserver variability in DOI measurement and its effect on tumor stage. We performed an electronic medical record search for excisions of squamous cell carcinoma of the oral cavity between January 1, 2010 and December 25, 2017. All slides containing significant tumor were selected for independent blinded DOI measurement by four head and neck pathologists per AJCC8 guidelines. Pathologic stage was assigned in conjunction with reported tumor greatest dimension. Observers recorded the slide used for measurement and potential issues limiting assessment of DOI. Results were compared for reproducibility in DOI and tumor stage using intraclass correlation coefficient (ICC) analysis. A total of 167 cases of oral squamous cell carcinoma with available slides were included. The ICC score for DOI between observers was 0.91339 (> 0.9 considered excellent). Only 7.2% of cases had uniform DOI amongst observers. Increasing overall tumor size and average DOI correlated with increasing range in DOI amongst observers. Differences in DOI resulted in differences in pathologic tumor staging (pT) for 15% of tumors. Use of different slides for DOI measurements was significantly associated with different pT staging. In contrast, ulceration and exophytic growth did not correlate with higher DOI or pT variability. Despite the excellent ICC score, differences in DOI measurement resulted in variable pT staging for a considerable number of cases. We therefore recommend consensus for DOI in at least some cases in which potential differences in DOI could alter pT stage assignment.

Genomic analysis of the first laboratory-mouse papillomavirus.

A papillomavirus (PV) that naturally infects laboratory mice will provide an extremely valuable tool for PV research. We describe here the isolation, cloning and molecular analysis of the first novel laboratory-mouse PV, designated MusPV. This agent, recently identified in the tissues from florid and asymmetrical papillomas on the face of nude mice (NMRI-Foxn1(nu)/Foxn1(nu)), was demonstrated to be transmissible to immunocompetent mice (Ingle et al., 2010). The MusPV genome is 7510 bp in length, is organized similarly to those of other PVs and has at least seven ORFs (E1, E2, E4, E6, E7, L1 and L2). Phylogenetic analysis indicates that MusPV belongs to the π genus together with four other rodent PVs (McPV2, MaPV1, MmiPV and RnPV1). Of the rodent PVs, MusPV appears most closely related to Mastomys coucha PV (McPV2), with 65 % genomic homogeneity and 80 % L1 amino acid similarity. Rodent PVs, except for MnPV1, do not contain any identifiable retinoblastoma protein (RB) binding sites. MusPV has one putative RB-binding site on the E6 protein but not on the E7 protein. Non-coding regions (NCRs) of PVs maintain multiple binding sites for transcription factors (TFs). The NCR of MusPV has numerous sites for TF binding, of which at least 13 TFs are common to all PVs in the π genus. MusPV provides a potentially valuable, novel mouse model to study mechanisms of infection, oncology and novel preventive and therapeutic approaches in mice that can be translated to diseases caused by human PVs.

The propeptide of cathepsin D increases proliferation, invasion and metastasis of breast cancer cells.

Expression and secretion of procathepsin D (pCD) increases proliferation, metastasis and progression of breast cancer but the structural moiety by which pCD exerts these effects is still ambiguous. Here, we present data on a series of pCD stable mutants to identify the pCD region that mediates this mitogenic effect. Mutations affecting the region of the activation peptide (AP) were studied together with catalytic and glycosylation mutants. Mitogenic effect was evaluated using in vitro invasion and proliferation assays and in vivo by determining the tumorigenic potential. The catalytic mutants and glycosylation mutants of pCD continued to display enhanced cell proliferation, invasion and tumorigenicity similar to stable transfectants of native pCD, suggesting that neither the proteolytic activity nor the sugar moieties contribute to the mitogenic effect. However, stable transfectants of pCD lacking its AP and with various mutations in the 27-44 amino acid region of AP, failed to show enhanced cell proliferation or invasion in vitro and tumor growth in vivo, establishing the importance of AP region. Our study concludes that the entire 27-44 amino acid region of AP is necessary for the stimulatory actions of pCD on breast cancer cells.

Depletion of procathepsin D gene expression by RNA interference: a potential therapeutic target for breast cancer.

Elevated level of procathepsin D (pCD), a zymogen of lysosomal aspartic proteinase cathepsin D, is associated with highly invasive neoplasms that include breast cancer. Independent studies have established that secreted pCD functions as a growth factor acting both in an autocrine and paracrine manner. Therefore, to explore whether pCD can be employed as a therapeutic target, the present study evaluates the impact of pCD knockdown using RNA interference technology. Of the three siRNA oligos tested, siRNA-3 exhibited a 90% inhibitory effect on pCD gene expression. Stable attenuation of pCD in breast cancer cells MDA-MB-231 was achieved by using a plasmid vector-based shRNA system. Pronounced suppression of pCD expression was accompanied by a significant reduction in invasion and proliferation of MDA-MB-231 cells stably transfected with functional shRNA. Importantly, in the athymic nude mice model, downregulation of pCD in breast cancer cells significantly reduced their metastatic potential. In addition, we observed a reduction in Cdc42 and NFkappaB2 expression in MDA-MB-231 cells with decreased pCD expression. When combined, our in vitro and in vivo experiments demonstrate that targeting pCD through RNAi technology represents a potential therapeutic tool for developing a therapy against breast cancer.

Development of cystic glandular hyperplasia of the endometrium in Mullerian inhibitory substance type II receptor-pituitary tumor transforming gene transgenic mice.

The pituitary tumor transforming gene (PTTG)/securin is an oncogene that is involved in cell cycle regulation and sister chromatid separation. PTTG is highly expressed in various tumors including ovarian tumors, suggesting that PTTG may play a role in ovarian tumorigenesis. Overexpression of PTTG resulted in induction of cellular transformation in vitro and tumor formation in nude mice. To ascertain PTTG function in ovarian tumorigenesis, we generated a transgenic mouse model of PTTG by cloning PTTG cDNA downstream of Mullerian inhibitory substance type II receptor gene promoter (MISIIR) in order to target the ovarian surface epithelium. By screening of transgenic animals, we identified five founders (four males and one female). Using the four male founders, we developed four transgenic lines. PTTG expression was increased in ovarian surface epithelium, ovarian granulosa cells, as well as in the pituitary gland. Transgenic females did not develop any visible ovarian tumors at 8-10 months of age; however, there was an overall increase in the corpus luteum mass in transgenic ovary, suggesting increased luteinization. These changes were associated with an increase in serum LH and testosterone levels. In addition, there was a generalized hypertrophy of the myometrium of MISIIR-PTTG transgenic uteri with cystic glandular and hyperplasia of the endometrium. Based on these results, we conclude that the overexpression of PTTG may be required to initiate precancerous conditions but is not sufficient to induce ovarian tumorigenesis and may require another partner to initiate cellular transformation.

Ribozyme-targeting procathepsin D and its effect on invasion and growth of breast cancer cells: an implication in breast cancer therapy.

Procathepsin D (pCD), a zymogen of lysosomal aspartic peptidase cathepsin D, overexpression is correlated with highly invasive malignancies, including breast cancer. Recently, different studies have shown the role of secreted pCD as mitogen acting both in an autocrine and a paracrine manner. The aim of the present study is to examine the anti-tumor effects elicited by a decrease in the protein level of pCD by ribozyme and to explore the therapeutic potential of this specific targeting. Using the mFold program, we designed seven anti-pCD ribozymes and checked the accessibility to target pCD mRNA by RNase H cleavage experiment in a cell-free system. The sequences of the 4 most effective ribozymes were cloned and stably transfected in a highly metastatic human breast cancer cell line, MDA-MB-231, to knock down the expression of pCD. Downregulation of pCD due to ribozyme expression was observed by Western blotting and real-time RT-PCR. Stably transfected cells with anti-pCD ribozymes exhibited a significant lowering of in vitro invasion (p<0.001) and reduction in lung colonization potential in nude mice when compared to control ribozyme transfected cells. We also found that downregulation of pCD by ribozyme promotes apoptosis of MDA-MB-231 cells on serum deprivation. These results suggest that we have generated a biologically functional ribozyme against pCD with possible therapeutic implications in breast cancer cells.

Leukotriene B4-receptor-1 mediated host response shapes gut microbiota and controls colon tumor progression.

Inflammation and infection are key promoters of colon cancer but the molecular interplay between these events is largely unknown. Mice deficient in leukotriene B4 receptor1 (BLT1) are protected in inflammatory disease models of arthritis, asthma and atherosclerosis. In this study, we show that BLT1-/- mice when bred onto a spontaneous tumor (ApcMin/+) model displayed an increase in the rate of intestinal tumor development and mortality. A paradoxical increase in inflammation in the tumors from the BLT1-/-ApcMin/+ mice is coincidental with defective host response to infection. Germ-free BLT1-/-ApcMin/+ mice are free from colon tumors that reappeared upon fecal transplantation. Analysis of microbiota showed defective host response in BLT1-/- ApcMin/+ mice reshapes the gut microbiota to promote colon tumor development. The BLT1-/-MyD88-/- double deficient mice are susceptible to lethal neonatal infections. Broad-spectrum antibiotic treatment eliminated neonatal lethality in BLT1-/-MyD88-/- mice and the BLT1-/-MyD88-/-ApcMin+ mice are protected from colon tumor development. These results identify a novel interplay between the Toll-like receptor mediated microbial sensing mechanisms and BLT1-mediated host response in the control of colon tumor development.

Acute limb ischemia associated with type B aortic dissection: clinical relevance and therapy.

BACKGROUND: The goal of the current study is to characterize the presentation, therapy, and outcomes of acute limb ischemia (ALI) associated with type B aortic dissection (AoD). METHODS: The prospective/retrospective International Registry for Acute Aortic Dissection (IRAD) database and a single institutional database were queried for all patients with type B AoD from 1996 to 2002. Univariate and multivariate statistics were used to delineate factors associated with morbidity and mortality outcomes. RESULTS: According to the IRAD data (n = 458), the mean age of patients was 64 years, and 70% were men. The overall mortality was 12%; of these, 6% had ALI. Pulse (3-fold) and neurologic deficits (5-fold) were more common in those with ALI (P < .001). Endovascular, but not surgical therapy, was more commonly performed in patients with ALI compared with those without ALI (31% vs 10%, P = .004). No difference in age, race, gender, or origin of dissection was observed. ALI was associated with acute renal failure (odds ratio [OR] = 2.7; 95% confidence interval [CI] 1.1-7.1; P = .048) and acute mesenteric ischemia/infarction (OR = 6.9; 95% CI 2.5-20; P < .001). Adjusting for patient characteristics, ALI was associated with death (3.5; 95% CI 1.1-10; P = .02). The single institution analysis revealed similar patient demographics and mortality in 93 AoD patients, of whom 28 had ALI. Aortic fenestration or aorto-iliac stenting was the primary therapy in 93%; surgical bypass was used in 7%. Limb salvage was 93% in those with ALI at a mean of 18 months follow-up. The number of organ systems with malperfusion was 2-fold higher at aortography than suspected preprocedure (P = .002). By stepwise regression modeling, mortality was greater in those not taking a beta-blocker (OR = 19; 95% CI 3.1-111; P = .001). CONCLUSIONS: ALI secondary to AoD is predictive of death and visceral ischemia. Endovascular therapy confers excellent limb salvage and allows diagnosis of unsuspected visceral ischemia.

Role of activation peptide of procathepsin D in proliferation and invasion of lung cancer cells.

BACKGROUND: Procathepsin D (pCD) secreted by cancer cells, increases proliferation, metastasis and progression of breast cancer, however its role in lung cancer is still unclear. The purified pCD and its synthetic activation peptide (AP) have shown similar proliferative effect on various cancer cell lines. The aim of this study is to clarify the role ofpCD and its AP in lung cancer by stable expression of pCD and pCD lacking its AP, in NCI-H23 lung cancer cells. MATERIALS AND METHODS: The stable transfected clones were tested for cell proliferation, invasion and growth in nude mice. The effect of exogenous addition of purified pCD and its mutant proteins was also analyzed by proliferation assay. RESULTS: The invasion and proliferation in vitro and tumor growth in vivo, demonstrated that the expression of pCD enhances the carcinogenic properties of NCI-H23 cells and that the AP is essential for these activities. Exogenous addition of purified proteins on various lung cancer cell lines showed that neither catalytic activity nor glycosylation are involved in the growth-promoting activity. CONCLUSION: This is the first report of pCD cDNA expression in lung cancer cells that enhances the growth and invasion of these cells both in vitro and in vivo.

Müllerian Remnant Cyst as a Cause of Acute Abdomen in a Female Patient with Müllerian Agenesis: Radiologic and Pathologic Findings.

We report a case of a 17-year-old female with Müllerian agenesis who presented with right sided abdominal pain clinically suspicious for acute appendicitis. Multimodality imaging workup revealed a heterogeneous cystic right upper quadrant mass with surrounding fluid and inflammatory changes. Surgical resection of this mass was performed and a histopathologic diagnosis of a hemorrhagic Müllerian remnant cyst was made, which to the best of our knowledge has never been described in a patient with Müllerian agenesis.

Thoracic outlet decompression for subclavian vein thrombosis: experience in 71 patients.

HYPOTHESIS: There is a difference in outcomes when patients have neurogenic thoracic outlet syndrome in addition to subclavian vein thrombosis. METHODS: Analysis of a prospectively developed database, medical record review, and a patient questionnaire were used to summarize clinical experience from December 1990 to December 2001 on the basis of the patient's original evaluation. Patients were stratified on the presence (group 1) or absence (group 2) of additional neurogenic pathologic features. RESULTS: Of 928 patients evaluated for thoracic outlet syndrome, 71 underwent 73 operative procedures for subclavian vein obstruction. Men predominated (55%), and the mean age was 32 years. Group 1 (41%) had more preoperative disability, a higher incidence of persistent pain (24%), and less likelihood of returning to full activity compared with group 2 (67% vs 93%; P = .01). Catheter-directed thrombolysis was used in 65% of veins. Preoperative balloon angioplasty was used selectively (34%), and only 4% required stents. Supraclavicular decompression and venolysis were usually delayed 3 weeks to allow for healing of the venous endothelium. Complications included wound infection (3%) and postoperative hematoma (8%). CONCLUSIONS: Patients with isolated subclavian vein obstruction have a more favorable outcome relative to those with combined neurogenic and venous pathologic features. Decompression following thrombolysis should be delayed to reduce the incidence of postoperative complications.