GENES, CHROMOSOMES AND CANCER, Issue 2 2005
Bruce Poppe
We present an extensive characterization of 10 B-cell lymphomas with a t(9;14)(p13;q32). The presence of the PAX5/IGH gene rearrangement was demonstrated by fluorescence in situ hybridization (FISH) using a validated probe set, whereas complex karyotypic changes were reassessed by multiplex-FISH (M-FISH). Pathologic and clinical review revealed the presence of this rearrangement in 4 histiocyte-rich, T-cell-rich B-cell lymphomas (HRTR-BCLs) and 2 posttransplantation diffuse large B-cell lymphomas (PTLD-DLBCLs). In contrast to initial observations describing this translocation in lymphoplasmacytic lymphoma (LPL) and LPL-derived large B-cell lymphoma, our data showed a wide morphologic and clinical spectrum associated with the PAX5/IGH rearrangement, pointing to an association between this aberration and a subset of de novo DLBCLs presenting with advanced disease and adverse prognosis. In addition, the recurrent incidence of this rearrangement in both HRTR-BCL (4 cases) and PTLD-DLBCL (2 cases) was previously unrecognized and is intriguing. © 2005 Wiley-Liss, Inc. [source]

Relationship of clinical and pathologic response to neoadjuvant chemotherapy and outcome of locally advanced breast cancer,

JOURNAL OF SURGICAL ONCOLOGY, Issue 1 2002
Csaba Gajdos MD
Abstract Background and Objectives Neoadjuvant chemotherapy in locally advanced breast cancers produces histologically evaluable changes and frequently reduces the size of the primary tumor. Local clinical response to neoadjuvant chemotherapy may correlate with response of distant metastases. Therefore, clinical or pathological factors, which predict or assess response to treatment, may predict outcome after consideration for initial extent of disease. Methods To identify pretreatment characteristics of locally advanced breast cancers which predict clinical and pathologic response to neoadjuvant chemotherapy as well as survival and to assess the utility of postoperative histologic changes, we retrospectively studied one hundred forty-four patients with locally advanced breast cancer treated with neoadjuvant chemotherapy between January 1975 and July 1996. Patients were identified through pathology records of the Mount Sinai Medical Center and via one of the author's clinical databases. Pathologic and clinical responses to neoadjuvant chemotherapy were correlated with survival. Stepwise logistic regression was used to identify variables most significantly related to clinical response and pathologic axillary lymph node involvement. Results Complete clinical response with no palpable tumor was noted in 7/86 patients (8%) and complete pathologic response was achieved in 18/138 patients (13%). Both clinical (P,=,0.038) and pathologic response (P,=,0.011) were related to tumor size at the time of diagnosis: smaller tumors were more likely to respond to chemotherapy than larger tumors. Histologic evidence of chemotherapeutic effect, i.e., cytoplasmic vacuolization, change in the number of mitoses and localized fibrosis in lymph nodes did not correlate with clinical or pathologically measured response. Clinical and pathologic response was not associated with age, histology, differentiation, or type of chemotherapy. No residual tumor was found in the axillary nodes of 27% (37) of the patients. Age and complete pathologic response were the only variables significantly related to pathologic nodal status. Eighty-four percent of the 61 patients under 50 years of age had nodal involvement compared to 65% of older patients (P,=,0.014). Fifty percent of complete pathologic responders had positive axillary lymph nodes compared to 76% of patients who did not have a complete pathologic response (P,=,0.020). Distant disease-free (P,=,0.039) and overall survival (P,=,0.035) were related to the number of involved axillary lymph nodes. After consideration for pathologic lymph node status, no other variable was significantly related to distant disease-free or overall survival in multivariate analysis. No variable was significantly related to local disease-free survival. Age, clinical tumor size, clinical lymph node status, clinical response, type of chemotherapy, histology, differentiation, chemotherapy effects on primary tumor and lymph nodes, decline in the number of mitoses, and degree of fibrosis in nodes were not predictive of distant recurrence or overall survival. Conclusions This study of patients treated with neoadjuvant chemotherapy for locally advanced breast cancers found little evidence that measurable clinical or pathologic changes attributable to chemotherapy predicted survival. Axillary lymph node status, associated with young age, was the most important prognostic indicator in these patients. J. Surg. Oncol. 2002;80:4,11. © 2002 Wiley-Liss, Inc. [source]

Differential Classification of Acute Myocardial Infarction into ST- and Non-ST Segment Elevation Is Not Valid or Rational

ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2010
Brendan Phibbs M.D., F.A.C.C.
Background: The distinction between ST elevation and nonST elevation infarcts is widely accepted and is employed as a guide to management. Aim: This is review of the world literature to assess the basis for this distinction, since the two studies on which it is based are seriously flawed in method and conclusions. Method: Pathologic and clinical studies were reviewed from the world literature. Finding: The pathology of the two subsets is identical as are the morbidity, mortality and clinical course. Non-ST elevation infarcts are likely to be subsequent, to occur in older patients and to involve the circumflex artery: this subset therefore includes a high-risk group. ST deviation in any part of the electric field of the heart will predictably be accompanied by reciprocal deviation if the entire field of the heart is mapped. Further, ST deviation of infarction is often transient, resolving in minutes so that infarcts will be predictably misclassified. ST deviation per se is therefore not a rational basis for classification of infarcts. In fact, invasive therapy is indicated in both subsets with identical results. Conclusion: The distinction between ST elevation and non-ST elevation infarcts is baseless. The high risk subgroup included in the non-ST elevation infarct set should not be denied the benefit of early invasive therapy. Ann Noninvasive Electrocardiol 2010;15(3):191,199 [source]

Genetic skeletal disorders of the fetus and infant: Pathologic and molecular findings in a series of 41 cases,

BIRTH DEFECTS RESEARCH, Issue 10 2009
Anastasia E. Konstantinidou
Abstract BACKGROUND: Genetic skeletal disorders of the fetus and infant are a large group of genetic disorders, comprising the groups formerly assigned as skeletal dysplasias (osteochondrodysplasias), dysostoses, and malformation syndromes with a skeletal component. Genetic skeletal disorders may be prenatally detected by ultrasonography or result in intrauterine or early postnatal death, constituting one difficult diagnostic field met by the pathologist who performs the perinatal autopsy. METHODS: In this retrospective study, we have gathered radiologic, physical, histopathologic, and molecular data regarding 41 cases of genetic skeletal disorders diagnosed among 1980 fetal and perinatal autopsies over a 10-year period. RESULTS: Our series of cases were classified according to the 2006 Nosology and Classification of Genetic Skeletal Disorders. The overall frequency of genetic skeletal disorders was 1:48 autopsies. The FGFR3 group and osteogenesis imperfecta type 2 were the more frequently encountered disorders. The mean gestational age at autopsy was 21.9 weeks (range, 12,37 weeks). A final diagnosis was obtained in 95% of cases. Genetic skeletal disorders were detected by prenatal ultrasound in 90% of cases, with a correct typing of the disorder achieved in only 34%. Molecular analysis was confirmative in 5 cases. CONCLUSIONS: The central role of the perinatal pathologist in collaboration with specialized services is essential for the correct interpretation of the radiologic, physical, and histopathologic findings, to accurately classify specific types of genetic skeletal disorders and enable genetic counseling. Birth Defects Research (Part A), 2009. © 2009 Wiley-Liss, Inc. [source]

Histopathologic grading of medulloblastomas

CANCER, Issue 2 2002
A Pediatric Oncology Group Study
Abstract BACKGROUND Medulloblastomas are small cell embryonal tumors of the cerebellum found predominantly in children, only slightly more than half of whom survive. Predicting favorable outcome has been difficult, and improved stratification clearly is required to avoid both undertreatment and overtreatment. Patients currently are staged clinically, but no pathologic staging system is in use. Two rare subtypes at extreme ends of the histologic spectrum, i.e., medulloblastomas with extensive nodularity and large cell/anaplastic medulloblastomas, are associated with better and worse clinical outcomes, respectively. However, there is little data about correlations between histologic features and clinical outcome for most patients with medulloblastomas that fall between these histologic extremes of nodularity and anaplasia. Therefore, the authors evaluated the clinical effects of increasing anaplasia and nodularity in a large group of children with medulloblastomas, hypothesizing that increasing nodularity would predict better clinical outcomes and that increasing anaplasia would presage less favorable results. METHODS Medulloblastomas from 330 Pediatric Oncology Group patients were evaluated histologically with respect to extent of nodularity, presence of desmoplasia, grade of anaplasia, and extent of anaplasia. Pathologic and clinical data were then compared using Kaplan,Meier and log-rank analyses. RESULTS Increasing grade of anaplasia and extent of anaplasia were associated strongly with progressively worse clinical outcomes (P < 0.0001 for both). Significant anaplasia (moderate or severe) was identified in 24% of medulloblastoma specimens. Neither increasing degrees of nodularity nor desmoplasia were associated significantly with longer survival. CONCLUSIONS Moderate anaplasia and severe anaplasia were associated with aggressive clinical behavior in patients with medulloblastomas and were detected in a significant number of specimens (24%). Pathologic grading of medulloblastomas with respect to anaplasia may be of clinical utility. Cancer 2002;94:552,60. © 2002 American Cancer Society. [source]

TOWARD THE GLOBAL STANDARDIZATION OF ENDOSCOPIC SUBMUCOSAL DISSECTION PROPOSAL FOR 10 YEARS FROM NOW , PRESENT AND FUTURE VIEW OF KOREA

DIGESTIVE ENDOSCOPY, Issue 2009
Joo Young Cho
Endoscopic submucosal dissection (ESD) is the main treatment of early gastric cancer in Korea. The Korean Society of Gastrointestinal Endoscopy (KSGE) has organized an ESD research group and made several plans to standardize pathologic and therapeutic points of view. This article is to introduce the present and future view of ESD in Korea. [source]

The Blood,Brain Barrier and Epilepsy

EPILEPSIA, Issue 11 2006
Emily Oby
Summary:, During the past several years, there has been increasing interest in the role of the blood,brain barrier (BBB) in epilepsy. Advances in neuroradiology have enhanced our ability to image and study the human cerebrovasculature, and further developments in the research of metabolic deficiencies linked to seizure disorders (e.g., GLUT1 deficiency), neuroinflammation, and multiple drug resistance to antiepileptic drugs (AEDs) have amplified the significance of the BBB's relationship to epilepsy. Prior to 1986, BBB research in epilepsy focused on three main areas: ultrastructural studies, brain glucose availability and transport, and clinical uses of AEDs. However, contrast-based imaging techniques and medical procedures such as BBB disruption provided a framework that demonstrated that the BBB could be reversibly disrupted by pathologic or iatrogenic manipulations, with important implications in terms of CNS drug delivery to "multiple drug resistant" brain. This concept of BBB breakdown for therapeutic purposes has also unveiled a previously unrecognized role for BBB failure as a possible etiologic mechanism in epileptogenesis. Finally, a growing body of evidence has shown that inflammatory mechanisms may participate in the pathological changes observed in epileptic brain, with increasing awareness that blood-borne cells or signals may participate in epileptogenesis by virtue of a leaky BBB. In this article we will review the relationships between BBB function and epilepsy. In particular, we will illustrate consensus and divergence between clinical reality and animal studies. [source]

Mouse models for human head and neck squamous cell carcinomas

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2006
Shi-Long Lu MD
Abstract Mouse models of human cancer play an important role in understanding the mechanisms of carcinogenesis and have accelerated the search for finding new molecular targets for cancer therapy. However, genetically engineered mouse models for head and neck squamous cell carcinoma (HNSCC) have only recently overcome major technical obstacles and begun to be explored. Here we review the current progress in the development of mouse models for human HNSCC, with emphasis on conditional transgenic and knockout mouse models. These new models faithfully recapitulate human HNSCC at both the pathologic and molecular levels. These animal models will not only be useful to define the roles of specific genes in HNSCC development and progression but will also provide a unique tool for developing and testing new therapeutic approaches. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source]

Long-term survival in locally advanced oral cavity cancer: An analysis of patients treated with neoadjuvant cisplatin-based chemotherapy followed by surgery,

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2005
Enzo Maria Ruggeri MD
Abstract Background. Neoadjuvant chemotherapy has been reported to be extremely active in head and neck cancer but has failed to give a statistically significant improvement in survival. Methods. From 1981 to 1994, 33 operable patients with locally advanced oral cavity cancer received cisplatin-based chemotherapy before surgery. Postoperative radiotherapy was performed in high-risk patients. Results. The overall clinical and pathologic complete response rates to neoadjuvant chemotherapy were 48% and 30%, respectively. At a median follow-up of 7.0 years (range, 0.3,15.3+ years), the 5-year and 10-year overall survival rates were 54.5% and 39.5%, and the disease-specific median survival was 6.6 years for all patients (8.3 and 2.3 years for stages III and IV, respectively). The univariate analysis showed a positive relationship between survival and male sex (p = .05), pathologic (p = .02), and clinical (p = .03) complete response. The Cox proportional hazard regression model confirmed the independent prognostic value of the clinical response with a 4.67 (95% CI, 1.70,12.86) hazard ratio. A second primary tumor occurred in six patients (18%), with a median of occurrence of 9 years (range, 7,11 years). Conclusions. This study confirms the prolonged survival expectancy largely exceeding 5 years for selected patients with stage IV and for most with stage III locally advanced oral cavity cancer achieving a clinical and/or pathologic complete response to chemotherapy. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source]

Molecular characterization of epstein-barr virus and oncoprotein expression in nasopharyngeal carcinoma in Korea

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2004
Yoon Kyung Jeon MD
Abstract Background. We evaluated the characteristics of nasopharyngeal carcinoma in Korea, including its clinical, pathologic, and molecular features, especially emphasizing on the EBV strains involved, latent membrane protein 1 (LMP1) expression, and the alterations of matrix metalloproteinase 9 (MMP9) and E-cadherin expression. Methods. The presence of EBV was evaluated by EBER in situ hybridization, and the expression of LMP1, MMP9, and E-cadherin by immunohistochemistry. The characterization of EBV type and LMP1 variant was performed by PCR. Results. EBER was detected in 55 of 57 cases (96%) of nonkeratinizing carcinoma (NKC) and undifferentiated carcinoma, but in only four of nine cases (44%) of squamous cell carcinoma (SCC). EBER positivity was much higher in the group with nodal metastases (p = .003). The predominant strain of EBV infection was type A (81%) and a 30-bp deletion LMP1 variant (77%). All EBER-positive SCCs were infected with EBV type A. LMP1 expression was detected in 36 of 59 (61%) patients with latent EBV infection and MMP9 in 41 of these 59 (69%). LMP1 positivity was much higher among the patients aged 50 years and younger. MMP9 expression was associated with LMP1 expression (p = .008), and nodal and distant metastasis (p = .019, p = .045). Loss of E-cadherin expression was correlated with MMP9 and nodal metastasis. The survival rate was much lower in patients with a higher TNM classification, stage, and a histology of SCC. EBER positivity was associated with a better prognosis in the Kaplan-Meier test, but had no prognostic value by Cox regression analysis. Loss of E-cadherin expression and nodal metastasis were also correlated with local recurrence and distant metastasis. Conclusion. EBV type and LMP1 variant had no significant influence on the clinicopathologic properties of tumor. However, there was a tendency toward a better survival in the EBV type B group. Histology and clinical staging were the two most important prognostic factors. © 2004 Wiley Periodicals, Inc. Head Neck26: 573,583, 2004 [source]

Nasopharyngeal carcinoma in situ (NPCIS),pathologic and clinical perspectives

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2002
Martin Wai Pak FRCSEd(ORL)
Abstract Background Dysplasia or carcinoma in situ lesions (NPCIS) of the nasopharynx have rarely been reported. The prevalence, biologic behavior, and the transformation period of the pure preinvasive lesions have not been fully explained. Methods All cases of NPCIS were retrospectively reviewed during the period between 1990 and 2000. The clinical features of all cases were studied. The biopsy samples were examined using light microscopy and in situ hybridization (ISH) for EBV-encoded RNA (EBER). The sera taken before and after the transformation were analyzed for anti-viral capsid antigen (VCA) EBV titers and circulating cell-free EBV DNA concentration. Results Three cases of NPCIS were identified. Two of the three cases subsequently developed into invasive NPC after initial presentation. The interval of transformation varied from 40 to 48 months. In all three cases, the specimens showed abnormal findings on light microscopy and positive staining for EBER. Elevated anti-VCA titers were present in two of the preinvasive lesions. No cell-free EBV DNA was detected in the sera of these patients during the preinvasive phase of the disease. Conclusions Preinvasive NPC is a rare but distinct entity. Its transformation period can be as long as 4 to 5 years. Elevated anti-VCA titers, in the presence of abnormal cells on light microscopy, should alert the pathologist to perform ISH EBER studies to diagnose this rare condition. © 2002 Wiley Periodicals, Inc. [source]

Calcifying epithelial odontogenic (Pindborg) tumor with malignant transformation and metastatic spread

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2001
Michael J. Veness MB
Abstract Background Pindborg tumors (calcifying epithelial odontogenic tumors) are uncommon neoplasms of odontogenic origin most often located in the posterior mandible. First described in detail in 1955 by Pindborg, these tumors are considered benign but can be locally aggressive in nature, with recurrence rates of 10% to 15% reported. The malignant form of this tumor is exceedingly rare. Methods We describe the case of a 64-year-old woman initially treated for a painful infected left mandibular third molar. The patient underwent extraction of the tooth and excision of an associated soft tissue component. Subsequent histologic review identified a Pindborg tumor of the left posterior mandible. Results After initial excision, this tumor recurred twice, with the recurrences exhibiting a progression to a malignant Pindborg tumor (odontogenic carcinoma) with vascular invasion and spread to a cervical lymph node. Further treatment involved radical surgery and adjuvant radiotherapy. At last review 12 months after treatment, the patient was disease free. Conclusions This article describes only the second case of odontogenic carcinoma. The transformation from benign to malignant histologic findings has not previously been documented in this tumor. The salient clinical features of this case are presented along with supportive pathologic and radiologic evidence. © 2001 John Wiley & Sons, Inc. Head Neck 23: 692,696, 2001. [source]

Arrhythmogenic Right Ventricular Dyspiasia/Cardiomyopathy:

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2000
Need for an International Registry.
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a heart muscle disease characterized by peculiar right ventricular involvement and electrical instability that precipitates ventricular arrhythmias and sudden death. The purpose of the present consensus report of the Study Group of the European Society of Cardiology and the Scientific Council on Cardiomyopathies of the World Heart Federation is to review the considerable progress in our understanding of the etiopathogenesis, morbid anatomy, and clinical presentation of ARVD/C since its first description in 1977. This article will focus on the important hut still unanswered issues, mostly regarding risk stratification, clinical outcome, and management of affected patients. Because ARVD/C is relatively uncommon and any one center may have experience with only a few patients, an international registry is being established to accumulate information and enhance the numbers of patients that can be analyzed to answer the pending questions. The registry also will facilitate pathologic, molecular, and genetics research on the etiology and pathogenesis of the disease. Furthermore, availability of an international database will enhance awareness of this largely unrecognized condition among the medical community. Physicians are encouraged to enroll patients in the International Registry of ARVD/C. [source]

Role of sonography in diagnosing and staging invasive lobular carcinoma

JOURNAL OF CLINICAL ULTRASOUND, Issue 7 2004
Veronica L. Selinko MD
Abstract Purpose The goal of this study was to compare the sensitivity of sonography with that of mammography in the detection of invasive lobular carcinoma (ILC), to identify ILC's typical imaging characteristics, and to further show the important role of ultrasound in the staging and treatment planning of this elusive tumor. Methods We identified all patients with ILC seen at our institution from 1998 through 2001; 62 had pathologically proven pure ILC. We retrospectively reviewed and analyzed the sonographic appearances in correlation with mammographic, pathologic, and clinical findings. We reviewed the results of sonographic examinations of the nodal basins and fine-needle aspiration (FNA) of suspicious nodes and correlated them with initial clinical and final pathologic staging. We noted all cases of multicentricity or multifocality and analyzed the relative sensitivity of mammography and sonography according to tumor size. Results Sonography had a sensitivity of 98% versus 65% for mammography. The most common mammographic pattern was a spiculated mass or architectural distortion (39%). On sonography the most common pattern was a hypoechoic mass with (58%) or without (27%) shadowing. An infiltrative pattern was observed in 13% of the cases. Ultrasound-guided FNA confirmed disease was present in the axillary lymph nodes in 21% of the patients, and sonographic examination of the nodal basins resulted in a change of clinical staging from N0 to N1 in 75% and from N1 to N0 in 30% of the cases. Multicentricity/multifocality was identified sonographically and proved by FNA in 21% of patients. Conclusions Sonography has a much higher sensitivity than mammography in detecting ILC and therefore is an important adjunctive tool in the diagnosis of this form of cancer. Routine examination of node-bearing areas in patients with ILC proved useful in refining the disease staging. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:323,332, 2004 [source]

Correlation of color Doppler sonographic findings with pH measurements in gastroesophageal reflux in children

JOURNAL OF CLINICAL ULTRASOUND, Issue 4 2001
Hye Suk Jang MD
Abstract Purpose We conducted a prospective study of color Doppler sonography in children with suspected gastroesophageal reflux (GER). The purpose of this study was to compare the accuracy of color Doppler sonography with that of continuous 24-hour pH monitoring of the esophagus in diagnosing GER and to determine how to interpret the reflux episodes detected on color Doppler sonography in children at high risk for reflux. Methods Color Doppler sonography and 24-hour esophageal pH monitoring were performed in 54 children ranging in age from 2 months to 10 years (mean, 3 years). The stomach of each patient was filled for adequate gastric distention just before the color Doppler sonographic examination. We counted the number of reflux episodes over a period of 15 minutes. One day after the sonographic examination, the reflux was evaluated with esophageal pH monitoring, and the resultant reflux index (ReI) was obtained. The ReI was considered to be pathologic when it was equal to or greater than 11.99%. The number of refluxes on color Doppler sonography and the ReI were correlated for each patient. Results The 2 tests showed an 81.5% agreement in the detection of GER. When pH monitoring was taken as the reference test, color Doppler sonography had a high sensitivity (95.5%) for diagnosing GER but a very low specificity (11.0%), with a positive predictive value of 84.3% and a negative predictive value of 33.3%. There was no statistically significant correlation between the frequencies of GER detected on color Doppler sonography and the ReIs on pH monitoring (p = 0.1103). There was no correlation between the reflux grades on sonography and the ReI grades on pH monitoring (p = 0.422). Conclusions Color Doppler sonography is highly sensitive and easier to use than pH monitoring. Although there are no definite criteria for evaluating the severity of GER on color Doppler imaging, this modality may be useful in screening children for GER. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:212,217, 2001. [source]

Controlling the mass action of ,-synuclein in Parkinson's disease

JOURNAL OF NEUROCHEMISTRY, Issue 2 2008
Changyoun Kim
Abstract Parkinson's disease (PD) is an age-related neurodegenerative disease with unknown etiology. Growing evidence from genetic, pathologic, animal modeling, and biochemical studies strongly support the theory that abnormal aggregation of ,-synuclein plays a critical role in the pathogenesis of PD. Protein aggregation is an alternative folding process that competes with the native folding pathway. Whether or not a protein is subject to the aggregation process is determined by the concentration of the protein as well as thermodynamic properties inherent to each polypeptide. An increase in cellular concentration of ,-synuclein has been associated with the disease in both familial and sporadic forms of PD. Thus, maintenance of the intraneuronal steady state levels of ,-synuclein below the critical concentration is a key challenge neuronal cells are facing. Expression of the ,-synuclein gene is under the control of environmental factors and aging, the two best-established risk factors for PD. Studies also suggest that the degradation of this protein is mediated by proteasomal and autophagic pathways, which are two mechanisms that are related to the pathogenesis of PD. Recently, vesicle-mediated exocytosis has been suggested as a novel mechanism for disposal of neuronal ,-synuclein. Relocalization of the protein to specific compartments may be another method for increasing its local concentration. Regulation of the neuronal steady state levels of ,-synuclein has significant implications in the development of PD, and understanding the mechanism may disclose potential therapeutic targets for PD and other related diseases. [source]

L -NAME reverses quinolinic acid-induced toxicity in rat corticostriatal slices: Involvement of src family kinases

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 12 2007
Cinzia Mallozzi
Abstract Quinolinic acid (QA) is an endogenous excitotoxin acting on N -methyl- d -aspartate receptors (NMDARs) that leads to the pathologic and neurochemical features similar to those observed in Huntington's disease (HD). The mechanism of QA toxicity also involves free radicals formation and oxidative stress. NMDARs are particularly vulnerable to the action of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that can act as modulators of the activity of protein tyrosine kinases (PTKs) and phosphotyrosine phosphatases (PTPs). Because QA is able to activate neuronal nitric oxide synthase (nNOS) as well as to stimulate the NMDARs, we evaluated the effect of N,-Nitro- l -arginine-methyl ester (l -NAME), a selective nNOS inhibitor, on QA-induced neurotoxicity in rat corticostriatal slices. In electrophysiologic experiments we observed that slice perfusion with QA induced a strong reduction of field potential (FP) amplitude, followed by a partial recovery at the end of the QA washout. In the presence of l -NAME the recovery of FP amplitude was significantly increased with respect to QA alone. In synaptosomes, prepared from corticostriatal slices after the electrophysiologic recordings, we observed that l -NAME pre-incubation reversed the QA-mediated inhibitory effects on protein tyrosine phosphorylation pattern, c-src, lyn, and fyn kinase activities and tyrosine phosphorylation of NMDAR subunit NR2B, whereas the PTP activity was not recovered in the presence of l -NAME. These findings suggest that NO plays a key role in the molecular mechanisms of QA-mediated excitotoxicity in experimental model of HD. © 2007 Wiley-Liss, Inc. [source]

Correlation of basic fibroblast growth factor expression with the invasion and the prognosis of oral squamous cell carcinoma

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2006
Takashi Hase
Background:, The aim of this study was to evaluate the relationship between the expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in cancer cells and fibroblasts at the invasive front of oral squamous cell carcinoma (OSCC), and the pathologic and clinical characteristics. Methods:, Sections of 61 biopsy specimens of primary OSCC were immunostained to assess the expression of bFGF and FGFR-1 in cancer cells and fibroblasts at the invasive front. Results:, The bFGF and FGFR-1 expressions in the cancer cells were evident in all specimens, whilst, in fibroblasts, they were detected in 41 (67%) of 61 specimens. These expressions in the fibroblasts occurred notably more often in high-invasive OSCC specimens than low-invasive OSCC specimens. The prevalence of bFGF and FGFR-1 expressions in cases with lymph node metastasis was significantly higher (P < 0.05) than in cases without metastasis. Moreover, these expressions were well correlated with patient prognosis. Conclusion:, This study concludes that bFGF and FGFR-1 expressions in fibroblasts at the invasive front are linked to the mode of invasion and the prognosis in OSCC. [source]

Effect of aging and degeneration on disc volume and shape: A quantitative study in asymptomatic volunteers

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2006
Christian W. A. Pfirrmann
Abstract Debate continues on the effect of disc degeneration and aging on disc volume and shape. So far, no quantitative in vivo MRI data is available on the factors influencing disc volume and shape. The objective of this MRI study was to quantitatively investigate changes in disc height, volume, and shape as a result of aging and/or degeneration omitting pathologic (i.e., painful) disc alterations. Seventy asymptomatic volunteers (20,78 years) were investigated with sagittal T1- and T2-weighted MR-images encompassing the whole lumbar spine. Disc height was determined by the Dabbs method and the Farfan index. Disc volume was calculated by the Cavalieri method. For the disc shape the "disc convexity index" was calculated by the ratio of central disc height and mean anterior/posterior disc height. Disc height, disc volume, and the disc convexity index measurements were corrected for disc level and the individuals age, weight, height, and sex in a multilevel regression analysis. Multilevel regression analysis showed that disc volume was negatively influenced by disc degeneration (p,<,0.001) and positively correlated with body height (p,<,0.001) and age (p,<,0.01). Mean disc height and the disc convexity index were negatively influenced by disc degeneration but not by gender, weight, and height. Disc height was positively correlated with age (p,<,0.01). From the results of this study, it can be concluded that disc degeneration generally results in a decrease of disc height and volume as well as a less convex disc shape. In the absence of disc degeneration, however, age tends to result in an inverse relationship on disc height, volume, and shape. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source]

Is pleomorphic lobular carcinoma really a distinct clinical entity?

JOURNAL OF SURGICAL ONCOLOGY, Issue 5 2008
Claire L. Buchanan MD
Abstract Background Attempts to define the clinical behavior of pleomorphic lobular carcinoma (PLC) have been limited to small series, and clinical management strategies have yet to be established. We describe our experience with PLC as compared to classic ILC and invasive ductal carcinoma (IDC). Methods From 9/1996 to 5/2003, clinical and histopathologic data for 5,635 patients undergoing primary surgical treatment and sentinel lymph node biopsy for breast cancer were collected. Four hundred eighty one (8.5%) patients were diagnosed with ILC; 3,978 (70.6%) with IDC. Of those with ILC, 356 (74%) patients had material available for pathologic re-review and comprise our study population: 52 were classified as PLC; 298 were classified as classic ILC; and 6 cases were reclassified as IDC. We compared clinical, pathologic, and treatment factors for patients with PLC, ILC, and IDC using the Wilcoxon rank sum and Fisher's exact tests. Results PLC were larger than ILC and IDC (20 vs. 15 vs. 13, P,<,0.001), had more positive nodes (median 1 vs. 0 vs. 0, P,<,0.05) and more frequently required mastectomy (63.5% vs. 38.7% vs. 28.8%, P,<,0.001). In addition, more patients with PLC had developed metastatic disease compared to patients with ILC (11.5% vs. 3.7%, P,<,0.05). Conclusions These findings suggest that PLC is a distinct clinical entity that presents at a more advanced stage and may require more aggressive surgical and adjuvant treatment. J. Surg. Oncol. 2008;98:314,317. © 2008 Wiley-Liss, Inc. [source]

Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 46

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003
L Padua
Traditional outcome assessment in neurological diseases has always been based on physician-derived and instrumental findings. Over the last two decades, clinical and public health researchers emphasized the need for a thorough evaluation of concepts such as Health Related Quality of Life (HRQoL) to study the impact of chronic illnesses and their treatments on the patient's life. The most frequent inherited neuropathy is Charcot-Marie-Tooth disease (CMT). CMT Patients develop progressive weakness and sensory disturbances, becoming sometimes severely disabled even at very young age. In CMT clinic, neurophysiologic, pathologic and genetic evaluation, are considered fundamental to assess nerve involvement and diagnose, but how these findings are related to HRQoL and disability is not assessed. We propose a prospective follow-up (24,30 months) of CMT patients with multiple measurements of CMT. Besides conventional clinic, pathologic, neurophysiologic and genetic measurements we adopt validated patient-oriented measurements to assess HRQoL and disability. Aims of the study are: 1) to assess HRQoL and disability of CMT patients in a wide and well-represented sample and to evaluate the relationships between conventional parameters and the patient's perception of his own HRQoL and disability; 2) to evaluate natural history of HRQoL and disability in CMT, and to evaluate the predictive value of phenotype, genetic picture, neurophysiological and pathological pattern 3) to develop a national network and a database on CMT disease (this aim includes the standardization, based on a consensus validation process, of the most used terms and measurements in CMT and the development of a database software). In a preliminary reunion, the authors developed a dedicated database for patients affected by CMT. Details about this database will be presented. [source]

Recurrent hepatic lymphangiomatosis after orthotopic liver transplantation

LIVER TRANSPLANTATION, Issue 11 2007
Seong H. Ra
Hepatic lymphangiomatosis is a rare disease characterized by an abnormal lymphatic proliferation involving the liver alone, liver and spleen, or multiple organs. Hepatic lymphangiomatosis becomes symptomatic secondary to compression or replacement of the normal parenchyma, which can lead to liver failure. Resection and orthotopic liver transplantation (OLT) can be used as treatment for this disease. We herein describe a 42-year-old female who had undergone successful OLT for hepatic lymphangiomatosis with recurrent disease detected 19 yr later in the transplanted liver. This is, to our knowledge, the first described case of recurrent hepatic lymphangiomatosis after OLT. In conclusion, we discuss the clinical, radiologic, pathologic, and immunohistochemical findings and review other reported cases of hepatic lymphangiomatosis that have undergone OLT. Liver Transpl 13:1593,1597, 2007. © 2007 AASLD. [source]

Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumor

PEDIATRIC BLOOD & CANCER, Issue 3 2006
Norman E. Breslow PhD
Abstract Background The National Wilms Tumor Study (NWTS) constitutes a unique resource for study of clinical, pathologic, and epidemiologic features of Wilms tumor (WT). Procedure Data from NWTS-3,4,5 were compiled for 7,455 patients with tumors of favorable (FH) or anaplastic (AH) histology. The associations of birth weight (BW) and age-at-onset with gender, intralobar (ILNR), and perilobar (PLNR) nephrogenic rests, tumor focality, congenital malformation syndromes, and tumor histology were analyzed using descriptive statistics and linear regression. Results Mean BWs for male and female patients without PLNR were 3.52 and 3.36 kg, respectively, and for those with PLNR were 0.12 kg and 0.15 kg heavier. Mean age was 45 months for males with no rests whose tumors were unifocal and of triphasic favorable histology. ILNR or multifocality decreased the mean age by 18 and 10 months, respectively, whereas female gender, blastemal/FH or AH increased it by 3, 10, and 16 months. Over 90% of multifocal tumors occurred in the presence of demonstrated ILNR or PLNR or both. The apparent bimodality of the age distributions and later mean ages-at-onset for females with both unifocal and multifocal tumors were explained in part by the relative deficit in females of ILNR versus PLNR-associated tumors. Conclusions These observations support the view that there are multiple pathways to Wilms tumorigenesis. They will facilitate selection of informative subgroups of patients for molecular analysis that may serve to identify the putative pathway for the majority of patients who cannot be classified provisionally on the basis of ILNR or PLNR. Pediatr Blood Cancer 2006;47:260,267. © 2006 Wiley-Liss, Inc. [source]

Cystic fibrosis lung disease starts in the small airways: Can we treat it more effectively?

PEDIATRIC PULMONOLOGY, Issue 2 2010
Harm A.W.M. Tiddens MD
Abstract The aims of this article are to summarize existing knowledge regarding the pathophysiology of small airways disease in cystic fibrosis (CF), to speculate about additional mechanisms that might play a role, and to consider the available or potential options to treat it. In the first section, we review the evidence provided by pathologic, physiologic, and imaging studies suggesting that obstruction of small airways begins early in life and is progressive. In the second section we discuss how the relationships between CF transmembrane conductance regulator (CFTR), ion transport, the volume of the periciliary liquid layer and airway mucus might lead to defective mucociliary clearance in small airways. In addition, we discuss how chronic endobronchial bacterial infection and a chronic neutrophilic inflammatory response increase the viscosity of CF secretions and exacerbate the clearance problem. Next, we discuss how the mechanical properties of small airways could be altered early in the disease process and how remodeling can contribute to small airways disease. In the final section, we discuss how established therapies impact small airways disease and new directions that may lead to improvement in the treatment of small airways disease. We conclude that there are many reasons to believe that small airways play an important role in the pathophysiology of (early) CF lung disease. Therapy should be aimed to target the small airways more efficiently, especially with drugs that can correct the basic defect at an early stage of disease. Pediatr Pulmonol. 2010; 45:107,117. © 2010 Wiley-Liss, Inc. [source]

Aqueous extract of rhubarb stabilizes vulnerable atherosclerotic plaques due to depression of inflammation and lipid accumulation

PHYTOTHERAPY RESEARCH, Issue 7 2008
Yunfang Liu
Abstract The study evaluated the effect of the traditional Chinese medicine rhubarb on the stability of atherosclerotic plaque. Atherosclerotic lesions were induced in rabbits through balloon injury with a high-cholesterol diet and then were divided into a control group, a rhubarb group and a simvastatin group. At week 24 recombinant-p53 adenoviruses were locally delivered to the atherosclerotic plaques. At week 26 plaque rupture was triggered by the intra-arterial Chinese Russell's viper venom and histamine. Serological, ultrasonographic, pathologic, immunohistochemical and gene expression studies were performed. The results showed that the incidence of plaque rupture in the rhubarb group and the simvastatin group was significantly lower than that in the control group (42.86% and 35.71% versus 80.00%, both p < 0.05). Serum TC, LDL-C (p < 0.05,0.01), IMT (both p < 0.01), PA (both p < 0.01), PB (%) (both p < 0.01) and the mRNA and protein expressions of TLR2, TLR4 and NF- ,B (p < 0.05, 0.01, respectively) in the rhubarb group and the simvastatin group were significantly lower than those in the control group. In contrast, AIIc% (both p < 0.05) in the two treatment groups were significantly higher than those in the control group. These results suggest that rhubarb has antiatherosclerotic and plaque-stabilizing properties due to antiinflammation and lipid-lowering effects. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Pulmonary manifestations of light chain deposition disease

RESPIROLOGY, Issue 5 2009
Lisa RHO
ABSTRACT Light chain deposition disease (LCDD) is a rare condition characterized by extracellular light chain deposition in tissues. Patients commonly have an underlying plasma cell dyscrasia, and produce excess levels of monoclonal light chains. Renal involvement is the most common clinical manifestation. Rarely, light chains are deposited in the lung. We present the pathologic and radiographic findings of three patients with biopsy-proven pulmonary light chain disease and a review of the literature. [source]

History of Smoking is Associated with Younger Age at Diagnosis of Breast Cancer

THE BREAST JOURNAL, Issue 4 2010
Mathew C Abramowitz MD
Abstract:, Smoking tobacco has been associated with incidence, response and outcomes after treatment of some cancers. We hypothesized that tobacco use could result in an observable effect on breast cancer stage and characteristics at diagnosis. There were 6,000 patients with Tis-4, N0-3 breast cancers who presented to a comprehensive cancer center at initial diagnosis between 1970 and 2006. Patients were included who had a known smoking history, and subdivided into any tobacco use 2683 (45%) or never tobacco use 3317 (55%). Analyses were performed to evaluate the association of smoking with clinical, pathologic and treatment-related factors at cancer presentation. Median age at diagnosis for all breast cancers was 55 years, for nonsmokers was 56 years, for any smoking history was 55 years, and the subgroup of current smokers was 52 years. The difference in median age for current smokers versus nonsmokers was statistically significant (p < 0.0001). The probability of age <55 years at breast cancer diagnosis for any smoking history compared to nonsmokers was 1.2 for white patients (p < 0.0003) but 0.81 for black patients (p = 0.25). There was no statistically significant association between smoking and T stage, N stage, ER/PR status, or Her-2/neu status, although smokers were less likely to utilize breast-conserving treatment. Smoking was associated with a younger age at diagnosis and lower utilization of breast conservation, and observed in the subgroup of white patients but not black patients. Further efforts to clarify potential reasons for any racial differences and lower utilization of breast conservation with smoking are warranted. [source]

Fungus ball of the paranasal sinuses: Experience in 160 patients treated with endoscopic surgery

THE LARYNGOSCOPE, Issue 11 2009
Piero Nicolai MD
Abstract Objectives/Hypothesis: Herein we present our experience in the management of fungus ball (FB) of the paranasal sinuses. Preoperative imaging strategy and findings, surgical technique, and pathologic and microbiologic results are discussed. Study Design: Retrospective chart review of patients with FB of the paranasal sinuses who underwent endoscopic surgery at the Department of Otorhinolaryngology of the University of Brescia, Italy. Methods: From January 1990 to December 2006, 160 patients with sinonasal fungus ball were treated with a purely endoscopic approach. All patients underwent preoperative computed tomography (CT) and/or magnetic resonance (MR) imaging; an endo-oral dental x-ray or orthopantomography and odontological evaluation were also performed in patients with maxillary sinus localization. All removed material was sent for pathologic and microbiologic evaluation. All patients were prospectively followed with endoscopic control every 2 months during the first postoperative year and subsequently every 6 months. Results: The patient cohort included 118 females and 42 males, with an age from 19 to 85 years (mean, 52.7 years). FB was located in the maxillary sinus in 135 (84.4%) patients; in two cases both sinuses were affected. Sphenoid and ethmoid involvement was observed in 23 (14.4%) and 1 (0.6%) patients, respectively. Simultaneous ethmoid and sphenoid involvement was found in one (0.6%) case. In all patients complete removal of fungal debris was obtained through wide sinusotomy. No recurrence was observed. Conclusions: Endoscopic surgery is a safe and effective treatment for paranasal sinuses FB. A proper imaging study by MR and/or CT can address diagnosis, which is based upon detection of fungal hyphae at histology. Laryngoscope, 2009 [source]

Role of Computed Tomography Imaging in Predicting Response of Nasopharyngeal Carcinoma to Definitive Radiation Therapy

THE LARYNGOSCOPE, Issue 12 2006
Xuejun Ma MD
Abstract Purpose: The purpose of this study was to investigate the role of posttreatment computed tomography (CT) scans in assessing response of nasopharyngeal carcinoma (NPC) to definitive radiotherapy. Material and Methods: Between March 1999 and October 2003, a total of 132 consecutive patients with newly diagnosed NPC were studied. Sixty-one patients with AJCC stage I or II NPC were treated with radiation only; 71 patients with stage III or IV disease but no evidence of distant metastasis were treated with concurrent chemoradiotherapy. All patients received CT scans of the head and neck, nasopharyngoscopy, and biopsies of primary sites at 4 to 6 months after completion of radiotherapy. Clinical response of the primary tumor as determined by comparison of pre- and posttreatment CT scans was correlated to pathology results. Results: The median follow-up time for all patients was 25 months (range, 9,40 months). Radiologic progression was seen in five patients, stable disease in 18 patients, and radiographic partial (rPR) and complete responses (rCR) were seen in 67 and 42 patients, respectively, at 4 to 6 months of follow up. Biopsies of the nasopharynx were positive in six patients. For patients with rCR, two patients (4.8%) had positive biopsies. Four patients with residual disease (rPR, stable, or progressive disease) after treatment had positive biopsies. The positive and negative predictive values, sensitivity, and specificity of CT scans in evaluating the NPC response to radiotherapy were 0.04, 0.95, 0.67, and 0.32, respectively. Conclusions: Pathologic CR for nasopharyngeal carcinoma is usually evident at 4 to 6 months after definitive radiotherapy; however, there is no correlation between pathologic and radiographic response. Although longer follow up is required to define the relationship between radiographic and pathologic responses with respect to disease control, we find CT scan at 4 to 6 months after radiotherapy to be neither sensitive nor specific in predicting the response of primary NPC to radiotherapy. [source]

Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate cancer

THE PROSTATE, Issue 10 2007
Jinpei Kumagai
Abstract BACKGROUND Cytochrome P450s (CYPs) influence the biological effects of carcinogens, drugs and hormones including testosterones. Among them, Cytochrome P450 2B6 (CYP2B6) plays a critical role in the deactivation of testosterone. In the present study, we examined CYP2B6 expression in human prostate tissues and prostate cancer. METHODS Immunohistochemical analysis was performed in 98 benign and 106 malignant prostate tissues and patients' charts were reviewed for clinical, pathologic and survival data. We also investigated whether stable expression of CYP2B6 in LNCaP (human prostate cancer cell line) influences cellular proliferation. RESULTS CYP2B6 was abundantly expressed in the normal epithelial cells compared to the prostate cancer cells. Significant immunostaining of CYP2B6 was found in 75 of 106 samples (71%), in the cytoplasm of cancerous tissue samples. CYP2B6 immunoreactivity was inversely correlated with high Gleason score (P,<,0.001). Decreased immunoreactivity of CYP2B6 significantly correlated with poor prognosis (P,<,0.0001). Univariate and multivariate hazard analyses revealed a significant correlation of decreased CYP2B6 expression with poor cancer-specific survival (P,=,0.0028 and 0.0142, respectively). Furthermore, overexpression of CYP2B6 in LNCaP cells significantly decreased testosterone-induced proliferation. CONCLUSIONS These results demonstrated that decreased expression of CYP2B6 might play a role in the development of prostate cancer, and be useful as the prognostic predictor for human prostate cancer. Prostate 67: 1029,1037, 2007. © 2007 Wiley-Liss, Inc. [source]