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Histopathologic Analysis (histopathologic + analysis)
Selected AbstractsAmelioration of brain pathology and behavioral dysfunction in mice with lupus following treatment with a tolerogenic peptideARTHRITIS & RHEUMATISM, Issue 12 2009Smadar Lapter Objective Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is manifested by neurologic deficits and psychiatric disorders. The aim of this study was to examine SLE-associated CNS pathology in lupus-prone (NZB × NZW)F1 (NZB/NZW) mice, and to evaluate the ameliorating effects of treatment with a tolerogenic peptide, hCDR1 (human first complementarity-determining region), on these manifestations. Methods Histopathologic analyses of brains from lupus-prone NZB/NZW mice treated with vehicle, hCDR1, or a control scrambled peptide were performed. The messenger RNA expression of SLE-associated cytokines and apoptosis-related molecules from the hippocampi was determined. Anxiety-like behavior was assessed by open-field tests and dark/light transfer tests, and memory deficit was assessed using a novel object recognition test. Results Infiltration was evident in the hippocampi of the lupus-afflicted mice, and the presence of CD3+ T cells as well as IgG and complement C3 complex deposition was observed. Furthermore, elevated levels of gliosis and loss of neuronal nuclei immunoreactivity were also observed in the hippocampi of the mice with lupus. Treatment with hCDR1 ameliorated the histopathologic changes. Treatment with hCDR1 down-regulated the high expression of interleukin-1, (IL-1,), IL-6, IL-10, interferon-,, transforming growth factor ,, and the proapoptotic molecule caspase 8 in the hippocampi of the mice with lupus, and up-regulated expression of the antiapoptotic bcl -xL gene. Diseased mice exhibited increased anxiety-like behavior and memory deficit. Treatment with hCDR1 improved these parameters, as assessed by behavior tests. Conclusion Treatment with hCDR1 ameliorated CNS pathology and improved the tested cognitive and mood-related behavior of the mice with lupus. Thus, hCDR1 is a novel candidate for the treatment of CNS lupus. [source] In vivo real-time diagnosis of nasopharyngeal carcinoma in situ by contact rhinoscopyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2005Martin Wai Pak FRCSEd(ORL) Abstract Background. Nasopharyngeal dysplasia or nasopharyngeal carcinoma in situ (NPCIS) lesions have rarely been reported. Timely diagnosis of the preinvasive lesion may improve prognosis. Contact endoscopy has been documented to accurately differentiate normal cells of the nasopharynx from malignant cells and allows a real-time diagnosis of primary and recurrent nasopharyngeal carcinoma (NPC) in a clinical setting. However, the role of contact endoscopy in the diagnosis of NPCIS is unknown. Methods. The superficial cells of the nasopharynx in a patient with NPCIS were examined in vivo under local anaesthesia by use of a contact rhinoscope. The contact endoscopic findings were correlated with the histologic findings of the biopsy. Results. The atypical cells of the lesion were magnified and visualized under contact endoscopy. Histopathologic analysis of the biopsied tissue confirmed the presence of NPCIS staining positively for Epstein-Barr virus (EBV),encoded RNA (EBER). No cell-free EBV DNA was detected in the sera of the patient. Conclusions. Contact endoscopy can accurately identify the atypical cells of a tiny preinvasive lesion in the nasopharynx in a clinical setting, which may not be evident in routine imaging examination. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Fatal HHV6 infection in an immunocompromised patient presenting with skin involvementJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2010Anjela Galan Infection with human herpesvirus-6 (HHV6) has a broad distribution in the human population, with a seroprevalence approaching 100% worldwide. Primary infection takes place during childhood, after which the virus remains latent mostly in lymphocytes and monocytes at various sites. Immunosuppression can result in viral reactivation, associated with clinical sequelae and even death. We report a case of a disseminated HHV6 infection in a 53-year-old patient, who was immunocompromised after allogeneic bone marrow transplant treatment for acute lymphocytic leukemia. Initially, he presented with a macular eruption of the skin, followed by involvement of other sites. Histopathologic analysis of skin biopsies revealed superficial perivascular large atypical mononuclear cells with intranuclear and intracytoplasmic inclusions. Most affected cells labeled with antibodies to CD3 and CD43 as lymphocytes, and some labeled with CD68 as macrophages. Polymerase chain reaction (PCR) studies of the blood, skin, liver, colon, cerebrospinal fluid and brain were positive for HHV6 virus. Additionally, the serologic titers for HHV6 were high. Viral particles were also detected by electron microscopy (EM) in the colon. Although rare, HHV6 virus may be an important pathogen in immunocompromised patients, and may present initially in the skin. Awareness of this infection is critical to diagnosis in acute settings. Galan A, McNiff JM, Nam Choi J and Lazova R. Fatal HHV6 infection in an immunocompromised patient presenting with skin involvement. [source] Freehand iMRI-guided large-gauge core needle biopsy: A new minimally invasive technique for diagnosis of enhancing breast lesionsJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2001Bruce L. Daniel MD Abstract The lack of reliable methods for minimally invasive biopsy of suspicious enhancing breast lesions has hindered the utilization of contrast-enhanced magnetic resonance imaging (MRI) for the detection and diagnosis of breast cancer. In this study, a freehand method was developed for large-gauge core needle biopsy (LCNB) guided by intraprocedural MRI (iMRI). Twenty-seven lesions in nineteen patients were biopsied using iMRI-guided LCNB without significant complications. Diagnostic tissue was obtained in all cases. Nineteen of the 27 lesions were subsequently surgically excised. Histopathologic analysis confirmed that iMRI-guided LCNB correctly distinguished benign lesions from malignancy in 18 of the 19 lesions. The histology revealed by core biopsy was partially discrepant with surgical biopsy in 2 of the other 19 lesions. Freehand iMRI-guided LCNB of enhancing breast lesions is promising. Larger studies are needed to determine the smallest lesion that can be sampled reliably and to precisely measure the accuracy of iMRI-guided LCNB as a minimally invasive tool to diagnose suspicious lesions found by breast MRI. J. Magn. Reson. Imaging 2001;13:896,902. © 2001 Wiley-Liss, Inc. [source] Evaluation of gastric toxicity of indomethacin acid, salt form and complexed forms with hydroxypropyl-,-cyclodextrin on Wistar rats: histopathologic analysisFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2009A.C. Ribeiro-Rama Abstract Indomethacin (IM) is a non-steroidal anti-inflammatory drug which inhibits prostaglandin biosynthesis. It is practically insoluble in water and has the capacity to induce gastric injury. Hydroxypropyl-,-cyclodextrin (HP-,-CD) is an alkylated derivative of ,-CD with the capacity to form inclusion complexes with suitable molecules. IM is considered to form partial inclusion complexes with HP-,-CD by enclosure of the p -chlorobenzoic part of the molecule in the cyclodextrin channel, reducing the adverse effects. The aim of this paper is to evaluate the gastric damage induced by the IM inclusion complex prepared by freeze-drying and spray-drying. A total of 135 Wistar rats weighing 224.4 ± 62.5 g were put into 10 groups. They were allowed free access to water but were maintained fasted for 18 h before the first administration until the end of the experiment. IM acid-form, IM trihydrated-sodium-salt and IM-HP-,-CD spray and freeze-dried, at normal and toxic doses, were administered through gastric cannula once/day for 3 days. Seventy-two hours after the first administration, the animals were sacrificed and the stomachs collected and prepared for morphological study by using the haematoxylin-eosin technique. Lesion indexes (rated 0/4) were developed and the type of injury was scored according to the severity of damage and the incidence of microscopic evidence of harm. Microscopic assessment demonstrated levels of injury with index one on 10,25%. The type of complexation method had different incidence but the same degree. The results show that IM inclusion complexation protects against gastric injury, reducing the incidence and the maximum degree of severity from 4 to 1, with a better performance of the spray-dried complex. [source] Hepatocellular carcinoma occurring in nonfibrotic liver: Epidemiologic and histopathologic analysis of 80 French casesHEPATOLOGY, Issue 2 2000Marie-Pierre Bralet M.D., Ph.D. Hepatocellular carcinoma (HCC) occurring in nonfibrotic liver represents a rare, ill-defined subgroup of HCC without cirrhosis in which mechanisms of hepatocarcinogenesis remain unclear. The aim of our study was to assess epidemiological factors and detailed histopathologic changes in the nontumoral liver of patients developing such tumors. Of 330 HCCs resected in our institution between 1985 and 1998, we retrospectively analyzed 80 cases (53 men, 27 women; mean age, 51 ± 16 years) in which the nontumoral liver showed no (n = 28) or minimal (n = 52) portal fibrosis without any septal fibrosis. In the group with no portal fibrosis there was no male predominance, and patients were significantly younger (44 ± 19 years vs. 54 ± 14 years) than those with minimal portal fibrosis. Sixty-seven tumors were typical HCCs, 8 were of fibrolamellar type, and 5 were hepatocholangiocarcinomas. Mean tumor size was 10 ± 5 cm. Risk factors for HCC development were found in 30 patients: hepatitis B (n = 17) or C (n = 2) virus infections, alcohol consumption (n = 11), and hemochromatosis (n = 1). In the nontumoral liver, periportal and lobular necrosis, mild portal inflammation, steatosis, and iron overload were present in 15%, 57%, 52%, and 54% of cases, respectively. Liver cell changes were noted in 6%. This study emphasizes the need for strict criteria to classify HCC without cirrhosis. HCC in nonfibrotic liver is a distinct subgroup in which nontumoral liver shows nonspecific minimal changes without regeneration or premalignant lesion. Etiologic factors are often unidentified, although presence of HBV infection in 21% suggests a direct oncogenic role of this virus. [source] Endoscopic sonographic evaluation of the thickened gallbladder wall in patients with acute hepatitisJOURNAL OF CLINICAL ULTRASOUND, Issue 5 2003Moon Young Kim MD Abstract Purpose. Thickening of the gallbladder wall is often observed during abdominal sonographic examination in patients with acute hepatitis. However, there is rarely an opportunity for a histopathologic analysis of these structural changes. Endoscopic sonography (EUS) can accurately delineate the structure of the gallbladder wall and therefore may be useful for visualizing changes in the gallbladder wall in patients with acute hepatitis. Hence, we prospectively studied the ability of EUS to detect specific structural changes in the gallbladder wall in patients with acute hepatitis and examined the effect of high elevation of serum liver enzyme levels on the gallbladder wall. Methods. A study group of patients diagnosed with acute hepatitis who had gallbladder wall thickening and a control group of patients without acute hepatitis or gallbladder disease underwent EUS between May 1, 1999, and June 1, 2002. EUS was used to measure the thickness of the gallbladder wall and to visualize each of its layers. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of the patients with acute hepatitis were measured at the time of the EUS examination. Statistically significant differences were determined using an independent t test and the chi-squared test. A p value of less than 0.05 was considered statistically significant. Results. The acute hepatitis group comprised 28 men and 24 women with a mean age of 40.8 years. The control group comprised 25 men and 25 women with a mean age of 45.1 years. The mean gallbladder wall thickness ± standard deviation in the acute hepatitis group (6.3 ± 2.6 mm) was significantly greater than that in the control group (1.6 ± 0.4 mm; p < 0.01). The mean thickness of the gallbladder wall for patients in whom both the AST and the ALT levels were 500 U/l or higher (7.0 ± 2.6 mm) was significantly greater than that for patients with levels below 500 U/l (5.4 ± 2.3 mm; p < 0.05). In the acute hepatitis group, EUS showed thickened, well-defined muscular and serosal layers of the gallbladder wall in 24 of the patients and a diffusely thickened gallbladder wall, in which each layer was ill defined, in the other 28 patients. The mean thickness of the gallbladder wall for patients with the pattern of ill-defined layers was significantly greater than that for the patients with the pattern of well-defined layers (p < 0.05). The pattern of ill-defined layers was more common among patients in whom the serum AST and ALT levels were at least 500 U/l than among patients with levels below 500 U/l (p < 0.05). Conclusions. We propose that gallbladder wall thickening in patients with acute hepatitis is associated with prominent changes in the muscular and serosal layers. Patients with highly elevated serum liver enzyme levels are more likely to have gallbladder wall thickening and disruption of planes between the muscular and serosal layers than are patients with normal liver enzyme levels. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:245,249, 2003 [source] Basaloid neoplasms in nevus sebaceusJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2000Steven Kaddu Background: Nevus sebaceus (NS) (organoider nevus) may frequently be associated with the development of a number of benign and malignant neoplasms among which basaloid neoplasms are the most common. Histopathologic criteria for diagnosis and classification of basaloid proliferations arising in NS are still debated. Most previous investigators have considered them to represent mainly basal cell carcinomas (BCCs). On the contrary, a number of recent authors have proposed that most basaloid neoplasms in NS exhibit predominantly morphologic features implying benignancy, thus representing trichobalstomas (TBs). In this study, we attempted to characterize better the histopathologic features of basaloid neoplasms in NS in a large series based on current morphologic criteria. Methods: Three-hundred and sixteen cases of NS seen over 19 years were consecutively sampled and reviewed for basaloid neoplasms. Twenty-four cases of basaloid neoplasms in NS were identified and categorized based on current histopathologic criteria either as TB or BCC. For comparison of histopathologic features, 37 solitary TB were also studied. Results: Following histopathologic analysis, 22 cases were categorized as TB (91.6%, 10 males, 12 females; mean age 40.8 years, range 19,78 years) and 2 cases as BCC (8.4%, 1 male, 1 female; 32 years and 40 years). Clinical features in both groups were generally similar. The lesions presented exclusively on the head and neck as skin colored to pigmented papules or nodules within NS (scalp in 19 TB cases and 1 BCC case; face in 2 TB cases and 1 BCC case; neck in 1 TB case). Histopathologically, TB in NS were characterized by smooth-bordered basaloid aggregations with either a nodular and/or a superficial pattern, abundant fibrous stroma with focal clefts within the stroma, and prominent features of limited follicular differentiation (rudimentary follicular germs in concert with papillae). In contrast, BCC in NS showed basaloid aggregations that vary markedly in size and shape, scant fibrous stroma, focal mucinous clefts between basaloid aggregations and surrounding stroma, and lack of prominent rudimentary follicular germs in concert with papillae. Remarkably, sections in a few cases of TB showed features occasionally found in BCCs but presently widely considered to be unspecific (e.g., ulceration, cystic degeneration, and focal clefts between basaloid aggregations and surrounding stroma). Two cases of TB in NS were associated with a sebaceoma and 1 case with a desmoplastic trichilemmoma. Follow-up data in 14 TB cases and 2 BCC cases (mean follow-up 28.8 months; range 1 to 160 months) revealed no local recurrences or distant metastases. Conclusion: Our study confirms that the vast majority of the basaloid neoplasms arising in NS show clear-cut morphologic criteria for TB, whereas only a few cases display histopathologic features consistent with BCC. In a minority of cases, basaloid neoplasms with overall morphologic features of TB may present problems in diagnosis when they exhibit a few histopathologic features traditionally associated with BCC or when they occur in combination with other adnexal neoplasms. [source] Immunohistochemical Characterization of Hepatic Malondialdehyde and 4-Hydroxynonenal Modified Proteins During Early Stages of Ethanol-Induced Liver InjuryALCOHOLISM, Issue 6 2003Brante P. Sampey Background: Chronic ethanol consumption is associated with hepatic lipid peroxidation and the deposition or retention of aldehyde-adducted proteins postulated to be involved in alcohol-induced liver injury. The purpose of this study was to characterize hepatocellular formation of aldehyde-protein adducts during early stages of alcohol-induced liver injury. Methods: Female Sprague Dawley® rats were subjected to the intragastric administration of a low-carbohydrate/high-fat total enteral nutrition diet or a total enteral nutrition diet containing ethanol for a period of 36 days. Indexes of hepatic responses to ethanol were evaluated in terms of changes in plasma alanine aminotransferase activity, hepatic histopathologic analysis, and induction of cytochrome P-4502E1 (CYP2E1). Immunohistochemical methods were used to detect hepatic proteins modified with malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE) for subsequent quantitative image analysis. Results: After 36 days of treatment, rats receiving the alcohol-containing diet displayed hepatic histopathologies characterized by marked micro- and macrosteatosis associated with only minor inflammation and necrosis. Alcohol administration resulted in a 3-fold elevation of plasma alanine aminotransferase activity and 3-fold increases (p < 0.01) in hepatic CYP2E1 apoprotein and activity. Quantitative immunohistochemical analysis revealed significant (p < 0.01) 5-fold increases in MDA- and 4-HNE modified proteins in liver sections prepared from rats treated with alcohol. The MDA- or 4-HNE modified proteins were contained in hepatocytes displaying intact morphology and were colocalized primarily with microvesicular deposits of lipid. Aldehyde-modified proteins were not prevalent in parenchymal or nonparenchymal cells associated with foci of necrosis or inflammation. Conclusions: These results suggest that alcohol-induced lipid peroxidation is an early event during alcohol-mediated liver injury and may be a sensitizing event resulting in the production of bioactive aldehydes that have the potential to initiate or propagate ensuing proinflammatory or profibrogenic cellular events. [source] Mediastinal gastroenteric cyst in a neonate containing respiratory-type epithelium and pancreatic tissuePEDIATRIC PULMONOLOGY, Issue 12 2009Eleftherios Anagnostou MD Abstract Mediastinal gastroenteric cyst is an uncommon congenital malformation and a distinct histopathological entity within the family of foregut duplication cysts. This lesion is mainly encountered in neonates and infants. Histologically, it is characterized by double-layered smooth muscle wall and gastric lining mucosa. We report on a case of a 2-day-old girl, with a posterior mediastinal cystic mass associated with T3,T4 hemivertebrae, presenting with severe respiratory distress. The cyst was multilocular, surgically removed, and histopathologic analysis revealed that it was of gastroenteric type. However, in numerous areas of the lesion, respiratory-type epithelium was observed, as well as pancreatic tissue. After removal of the lesion the patient made an uneventful recovery and shows no signs of long-term pulmonary sequelae. We failed to demonstrate in the available literature the presence of this variable epithelial lining within a single mediastinal foregut cyst. In addition, pancreatic tissue within an intrathoracic enteric cyst has been reported only twice. Pediatr Pulmonol. 2009; 44:1240,1243. © 2009 Wiley-Liss, Inc. [source] Effect of aged garlic extract against methotrexate-induced damage to the small intestine in ratsPHYTOTHERAPY RESEARCH, Issue 6 2006Mehmet Yüncü Abstract Methotrexate (MTX) chemotherapy is often accompanied by side effects such as gastrointestinal ulceration and diarrhea. The aim of this study was to examine histologically whether an aged garlic extract (AGE) had a protective effect on the small intestine of rats with MTX-induced damage. Forty male Wistar albino rats were randomized into experimental and control groups and divided into four groups of ten animals. To the first group, MTX was applied as a single dose (20 mg/kg) intraperitoneally. To the second group, in addition to MTX application, AGE (250 mg/kg) was administered orally every day at the same time by intragastric intubation until the rats were killed. To the third group, AGE only was given. The fourth group was the control. All animals were killed 4 days after the intraperitoneal injection of MTX for histopathologic analysis and tissue MDA levels. Before killing, intracardiac blood was obtained from each animal to perform biochemical analysis (plasma lactate level). MTX was found to lead to damage in the jejunal tissues and to increase the MDA and lactate levels in the plasma. Administration of the AGE decreased the severity of jejunal damage, but increased MDA and lactate levels caused by MTX treatment on the other hand. These results suggest that AGE may protect the small intestine of rats from MTX-induced damage. Thus this study substantiated the thought that the protective effect of AGE is derived from the manner in which it interacts with crypt cells. Copyright © 2006 John Wiley & Sons, Ltd. [source] Pediatric squamous cell carcinoma: Case report and literature review,,THE LARYNGOSCOPE, Issue 8 2009Douglas Sidell MD Abstract Objectives/Hypothesis: Describe a rare pediatric malignancy. Discuss the clinical, diagnostic, and therapeutic differences between squamous cell carcinoma (SCC) of the adult and pediatric population. Study Design: Case report including a detailed radiological and histopathologic analysis and review of the literature. Methods: A case report is described from a tertiary care university hospital. Histopathologic assessment and radiological details are reviewed. A literature review of the background, incidence, disease course, and treatment options are presented. Results: This case report presents a 6-year-old male with a 2-month history of an enlarging oral lesion. The patient denied dysphagia, pain, weight loss, bleeding, or loosening of the teeth. Biopsy demonstrated invasive, well-differentiated, exophytic squamous cell carcinoma with perineural and angiolymphatic invasion. Computed tomography and magnetic resonance imaging demonstrated a 2.7 × 3.0 cm poorly marginated infiltrative mass involving the gingival aspect of the superior alveolar ridge and the adjacent bony marrow, primarily to the right of midline. Multiple small subcentimeter lymph nodes were also identified in the bilateral level II to V posterior cervical triangles bilaterally. Conclusions: Pediatric SCC of the oral cavity is indeed a rare entity; however, its presence in the pediatric population should not be ignored. This case report describes the occurrence of SCC in the oral cavity of a 6-year-old male patient, the youngest case ever reported, and is a reminder that a multidisciplinary approach tailored to pediatric individuals is essential to obtain clear diagnoses and appropriate treatment plans. [source] Image Cytometry DNA-Analysis of Fine Needle Aspiration Cytology to Aid Cytomorphology in the Distinction of Branchial Cleft Cyst from Cystic Metastasis of Squamous Cell Carcinoma: A Prospective Study,THE LARYNGOSCOPE, Issue 11 2004Sushma Nordemar MD Abstract Objective: Frequently, the distinction between branchial cleft cyst and cystic metastases from squamous cell carcinoma is difficult by cytomorphology. In a prospective study, we investigated the need for, and the value of, image cytometry DNA-analysis as a complement to cytologic evaluation of cystic lesions in the neck. Study Design: Image cytometry DNA-analysis was performed on the fine needle aspiration cytology smears from 50 patients, referred to our department, with a solitary cystic lesion in the lateral region of the neck. Methods: Smears from aspirates were Giemsa stained and cytologically evaluated. Ahrens image analysis was used for DNA analysis on smears stained with Schiff reagent, and lymphocytes were used as control cells. Epithelial cells with DNA values exceeding 5c were regarded as aneuploid, indicating malignancy. Results: Nine lesions were diagnosed as squamous cell cancer metastases cytologically. DNA analysis showed aneuploidy in all of them except one. Three of these lesions had earlier been diagnosed as branchial cleft cyst at the referring hospital. Eight lesions were cytologically inconclusive and four of them were revealed as cystic metastasis at histopathologic analysis, and DNA analysis showed aneuploidy in all but one, which could not be analyzed. Two of these lesions were also diagnosed as branchial cleft cysts at the referring hospital. All benign lesions were diploid. Nine lesions were thyroid and salivary gland lesions. Conclusion: Image cytometry DNA-analysis was shown to help in the distinction between benign and malignant cystic lesions. Thus, when conventional cytomorphology does not suffice, DNA-analysis is clearly a valuable supplement. [source] Cancer preceding giant cell arteritis: A case,control study,ARTHRITIS & RHEUMATISM, Issue 6 2010Tanaz A. Kermani Objective To study the association between previous cancer and giant cell arteritis (GCA). Methods Using the resources of the Rochester Epidemiology Project, we identified incident cases of GCA diagnosed between January 1, 1950 and December 31, 2004. Each GCA patient was matched for age, sex, and length of medical history to 2 subjects without GCA from the same population. Medical records were reviewed. Diagnosis of cancer was confirmed by histopathologic analysis. Results We identified 204 GCA cases and 407 controls. The GCA group included 163 women (80%) and 41 men (20%). Their mean ± SD age was 76.0 ± 8.2 years. The non-GCA group consisted of 325 women (80%) and 82 men (20%). Their mean ± SD age was 75.6 ± 8.4 years. At the index date, 45 GCA patients (22%) and 125 non-GCA patients (31%) had had a previous cancer. The odds ratio (OR) for previous cancer in cases compared with controls, adjusted for age, sex, and calendar year, was 0.63, and the 95% confidence interval (95% CI) was 0.42,0.94 (P = 0.022). The mean age at diagnosis of the first cancer before the index date was similar in the cases (67.5 ± 11.9 years) and the controls (64.9 ± 13.2 years) (P = 0.32). The mean ± SD duration from the first cancer to the index date was 9.8 ± 9.9 years in the cases and 11.7 ± 10.8 years in the controls (P = 0.31). Cancer types were similar in both groups, but fewer gynecologic malignancies were noted in GCA patients (OR 0.39 [95% CI 0.13,1.15], P = 0.09). Colon cancer also appeared less commonly in the cases compared with the controls (OR 0.22 [95% CI 0.03,1.74], P = 0.15). Conclusion The findings of this population-based case,control study indicate that GCA patients had significantly fewer malignancies prior to the index date as compared with controls. [source] Bim,Bcl-2 homology 3 mimetic therapy is effective at suppressing inflammatory arthritis through the activation of myeloid cell apoptosisARTHRITIS & RHEUMATISM, Issue 2 2010John C. Scatizzi Objective Rheumatoid arthritis (RA) is a destructive autoimmune disease characterized by an increased inflammation in the joint. Therapies that activate the apoptotic cascade may have potential for use in RA; however, few therapeutic agents fit this category. The purpose of this study was to examine the potential of Bim, an agent that mimics the action of Bcl-2 homology 3 (BH3) domain,only proteins that have shown success in preclinical studies of cancer, in the treatment of autoimmune disease. Methods Synovial tissues from RA and osteoarthritis patients were analyzed for the expression of Bim and CD68 using immunohistochemistry. Macrophages from Bim,/, mice were examined for their response to lipopolysaccharide (LPS) using flow cytometry, real-time polymerase chain reaction analysis, enzyme-linked immunosorbent assay, and immunoblotting. Bim,/, mice were stimulated with thioglycollate or LPS and examined for macrophage activation and cytokine production. Experimental arthritis was induced using the K/BxN serum,transfer model. A mimetic peptide corresponding to the BH3 domain of Bim (TAT-BH3) was administered as a prophylactic agent and as a therapeutic agent. Edema of the ankles and histopathologic analysis of ankle tissue sections were used to determine the severity of arthritis, its cellular composition, and the degree of apoptosis. Results The expression of Bim was reduced in RA synovial tissue as compared with controls, particularly in macrophages. Bim,/, macrophages displayed elevated expression of markers of inflammation and secreted more interleukin-1, following stimulation with LPS or thioglycollate. TAT-BH3 ameliorated arthritis development, reduced the number of myeloid cells in the joint, and enhanced apoptosis without inducing cytotoxicity. Conclusion These data demonstrate that BH3 mimetic therapy may have significant potential for the treatment of RA. [source] | |||||||||||||||||||