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Pathological Analysis (pathological + analysis)
Selected AbstractsOvercoming immunological tolerance to melanoma: Targeting CTLA-4ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2010F Stephen HODI Abstract The use of immunotherapeutics in melanoma has received much attention, and recent advances to further characterize the regulatory components of the immune system and the importance of co-stimulatory molecules have opened a new area for clinical investigation. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) serves as a negative regulator of immunity. Recent trials administering fully human anti-CTLA-4 monoclonal antibodies to melanoma patients have demonstrated clinically meaningful responses. Treatment with CTLA-4 blocking antibodies, however, is not without potential toxicities. Autoimmune side-effects, the most common being colitis-associated diarrhea, are frequently associated with clinical responses. In efforts to build upon prior vaccination efforts as well as attempt to offer patients clinically meaningful immune responses with a CTLA-4 blockade but without significant toxicities, we conducted a clinical trial in patients who previously received autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GVAX; Cell Genesys, South San Francisco, CA, USA) with periodic infusions of CTLA-4 blocking antibodies. This sequential treatment resulted in clinically significant anti-tumor immunity without grade 3 or 4 toxicity in most patients. Pathological analyses following treatment of pre-existing tumors revealed a linear correlation between tumor necrosis and the ratio of intra-tumoral CD8+ effector cells to FoxP3+ regulatory cells (Tregs). Effective anti-tumor immunity and serious autoimmunity can be disassociated. Further targeting of anti-tumor Tregsin combinatorial therapy approaches may be a rich avenue of future investigation. [source] A boy born with multiple lesions of atrophodermaACTA PAEDIATRICA, Issue 3 2010Piero Pavone Abstract Aims:, The Atrophodermas include a large group of disorders appearing as localized or widespread depressed skin areas and characterized by underlying dermal atrophy. The present study aims to report a peculiar form of previously unreported focal dermal atrophy. Methods:, We studied over a period of 5 years a boy who manifested, since birth, multiple hypopigmented cutaneous atrophic lesions of the atrophoderma type in a mosaic distribution over the body and the legs. Results:, This boy did no develop other cutaneous or systemic stigmata except for an idiopathic thrombocytopenic purpura (ITP) manifested at age 2 years. Full serum, metabolic and infective analyses; full ophthalmological examination; ultrasound examination of the heart and internal organs; skeletal x-rays; brain magnetic resonance imaging; and DNA analysis of the PORCN (Focal Dermal Hypoplasia - FDH) gene in this boy yielded normal results. Pathological analysis of multiple skin specimens from an affected area revealed slightly reduced dermal thickness; hyperpigmentation of the basal layer; homogenized and disarrayed collagen bundles; perivascular chronic infiltrates of lymphocytes and histiocytes; and normal skin appendages. Currently, the child is healthy; he has mildly improved skin status with less-evident skin depression throughout the lesion areas and no further complication has been recorded. The histological and clinical appearance of the skin lesions and the course were against any known disorder in the group of the atrophodermas. Conclusions:, The cutaneous lesions seen in this boy represent a possibly new congenital skin disorder characterized by multiple, benign areas of focal dermal atrophy in a mosaic distribution. [source] Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2001R. Gerlai Abstract Exogenous glial cell line-derived neurotrophic factor (GDNF) exhibits potent survival-promoting effects on dopaminergic neurons of the nigrostriatal pathway that is implicated in Parkinson's disease and also protects neurons in forebrain ischemia of animal models. However, a role for endogenous GDNF in brain function has not been established. Although mice homozygous for a targeted deletion of the GDNF gene have been generated, these mice die within hours of birth because of deficits in kidney morphogenesis, and, thus, the effect of the absence of GDNF on brain function could not be studied. Herein, we sought to determine whether adult mice, heterozygous for a GDNF mutation on two different genetic backgrounds, demonstrate alterations in the nigrostriatal dopaminergic system or in cognitive function. While both neurochemical and behavioural measures suggested that reduction of GDNF gene expression in the mutant mice does not alter the nigrostriatal dopaminergic system, it led to a significant and selective impairment of performance in the spatial version of the Morris water maze. A standard panel of blood chemistry tests and basic pathological analyses did not reveal alterations in the mutants that could account for the observed performance deficit. These results suggest that endogenous GDNF may not be critical for the development and functioning of the nigrostriatal dopaminergic system but it plays an important role in cognitive abilities. [source] Cellular repressor of E1A-stimulated genes attenuates cardiac hypertrophy and fibrosisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 7 2009Zhouyan Bian Abstract Cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein of 220 amino acids. It has been proposed that CREG acts as a ligand that enhances differentiation and/or reduces cell proliferation. CREG has been shown previously to attenuate cardiac hypertrophy in vitro. However, such a role has not been determined in vivo. In the present study, we tested the hypothesis that overexpression of CREG in the murine heart would protect against cardiac hypertrophy and fibrosis in vivo. The effects of constitutive human CREG expression on cardiac hypertrophy were investigated using both in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding and infusion of angiotensin II in CREG transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by two-dimensional and M-mode echocardiography as well as by molecular and pathological analyses of heart samples. Constitutive over-expression of human CREG in the murine heart attenuated the hypertrophic response, markedly reduced inflammation. Cardiac function was also preserved in hearts with increased CREG levels in response to hypertrophic stimuli. These beneficial effects were associated with attenuation of the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase 1 (MEK-ERK1)/2-dependent signalling cascade. In addition, CREG expression blocked fibrosis and collagen synthesis through blocking MEK-ERK1/2-dependent Smad 2/3 activation in vitro and in vivo. Therefore, the expression of CREG improves cardiac functions and inhibits cardiac hypertrophy, inflammation and fibrosis through blocking MEK-ERK1/2-dependent signalling. [source] Temporary Occlusion of the Great Cardiac Vein and Coronary Sinus to Facilitate Radiofrequency Catheter Ablation of the Mitral IsthmusJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2008ANDRE D'AVILA M.D. Introduction: Ablation of the mitral isthmus to achieve bidirectional conduction block is technically challenging, and incomplete block slows isthmus conduction and is often proarrhythmic. The presence of the blood pool in the coronary venous system may act as a heat-sink, thereby attenuating transmural RF lesion formation. This porcine study tested the hypothesis that elimination of this heat-sink effect by complete air occlusion of the coronary sinus (CS) would facilitate transmural endocardial ablation at the mitral isthmus. Methods: This study was performed in nine pigs using a 30 mm-long prototype linear CS balloon catheter able to occlude and displace the blood within the CS (the balloon was inflated with ,5 cc of air). Using a 3.5 mm irrigated catheter (35 W, 30 cc/min, 1 minute lesions), two sets of mitral isthmus ablation lines were placed per animal: one with the balloon deflated (CS open) and one inflated (CS Occluded). After ablation, gross pathological analysis of the linear lesions was performed. Results: A total of 17 ablation lines were placed: 7 with CS Occlusion, and 10 without occlusion. Despite similar biophysical characteristics of the individual lesions, lesion transmurality was consistently noted only when using the air-filled CS balloon. Conclusions: Temporary displacement of the venous blood pool using an air-filled CS balloon permits transmurality of mitral isthmus ablation; this may obviate the need for ablation within the CS to achieve bidirectional mitral isthmus conduction. [source] Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndromeMOVEMENT DISORDERS, Issue 8 2005Yoshio Tsuboi MD Abstract The objective of this study is to better define the pathological characteristics of pathologically proven progressive supranuclear palsy (PSP) presenting with the corticobasal syndrome (CBS). PSP is characterized by early falls, vertical supranuclear ophthalmoplegia, and axial rigidity, whereas asymmetric limb features, including rigidity, bradykinesia, apraxia, alien limb phenomena, and cortical sensory loss are characteristic of CBS. We investigated clinicopathological characteristics of 5 cases of PSP that presented with CBS (CBS-PSP). Comprehensive pathological analysis was undertaken to determine the presence of concomitant pathological processes as well as quantitative tau burden in cortical regions of CBS-PSP, compared with 8 typical PSP cases (Typ-PSP). The clinical features in the CBS-PSP cases included asymmetrical features, apraxia, alien limb phenomena, and progressive aphasia. All cases had Parkinsonism, and vertical supranuclear ophthalmoplegia was noted in all but 1 case of CBS-PSP. Secondary neuropathological diagnoses included argyrophilic grain disease (AGD) in 1 of the 8 cases of Typ-PSP, whereas Alzheimer's disease (AD), Lewy body disease, AGD, and vascular disease was found in 3 cases of CBS-PSP. Image analysis of cortical tau burden performed in 8 Typ-PSP and 3 CBS-PSP cases revealed a significant increased tau burden in mid-frontal and inferior-parietal cortices in the CBS-PSP cases. This study demonstrates that when PSP presents as CBS, it is most likely due to either a concurrent cortical pathology from a secondary process such as AD or from the primary pathology of PSP extending into cortical areas that are primarily and commonly affected in CBD. © 2005 Movement Disorder Society [source] Mapping of Atrial Activation Patterns After Inducing Contiguous Radiofrequency Lesions: An Experimental StudyPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2 2001FRANCISCO J. CHORRO CHORRO, F.J., et al.: Mapping of Atrial Activation Patterns After Inducing Contiguous Radiofrequency Lesions: An Experimental Study. High resolution mapping techniques are used to analyze the changes in atrial activation patterns produced by contiguous RF induced lesions. In 12 Langendorff-perfused rabbit hearts, left atrial activation maps were obtained before and after RF induction of epicardial lesions following a triple-phase sequential protocol: (phase 1) three separate lesions positioned vertically in the central zone of the left atrial wall; (phase 2) the addition of two lesions located between the central lesion and the upper and lower lesions; and (phase 3) the placement of four additional lesions between those induced in the previous phases. In six additional experiments a pathological analysis of the individual RF lesions was performed. In phase 1 (lesion diameter = 2.8 ± 0.2 mm, gap between lesions = 3 ± 0.8 mm), the activation process bordered the lesions line in two (2.0-ms cycles) and four experiments (1.0-ms cycles). In phase 2, activation bordered the lesions line in eight (2.0-ms cycles, P < 0.01 vs control) and nine experiments (1.0-ms cycles, P < 0.001), and in phase 3 this occurred in all experiments except one (both cycles, P < 0.001 vs control). In the experiments with conduction block, the increment of the interval between activation times proximal and distal to the lesions showed a significant correlation to the length of the lesions (r = 0.68, P < 0.05, 100-ms cycle). In two (17%) experiments, sustained regular tachycardias were induced with reentrant activation patterns around the lesions line. In conclusion, in this acute model, atrial RF lesions with intact tissue gaps of 3 mm between them interrupt conduction occasionally, and conduction block may be frequency dependent. Lesion overlap is required to achieve complete conduction block lines. Tachycardias with reentrant activation patterns around a lesions line may be induced. [source] Waldenstrom's macroglobulinemia presenting with spinal cord compression: A case reportAMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2006Hani Al-Halabi Abstract Waldenstrom's macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma characterized by a wide range of clinical presentations related to direct tumor infiltration and the production of IgM. Most commonly it presents with cytopenia, hepatosplenomegaly, lymphadenopathy, constitutional symptoms, and hyperviscosity syndrome. We report a case of WM in an 81-year-old man who initially presented with severe back pain. The patient had no peripheral lymphadenopathy or hepatosplenomegaly and his peripheral blood smear was normal. MRI of the spine revealed an epidural mass causing spinal cord compression at T9. Surgical decompression was performed and pathological analysis of the mass revealed a lymphoproliferative B-cell process. The diagnosis of WM was established after cytomorphologic and immunohistochemical analysis of the patient's bone marrow revealed the presence of a lymphoid/lymphoplasmacytoid-like bone marrow infiltrate along with an elevated serum IgM level. The patient responded both clinically and serologically to local radiotherapy. This case is unusual because the patient lacked all common clinical features of WM. This is the first reported case of epidural spinal cord compression as the initial manifestation of WM, adding to the spectrum of clinical presentations seen in this disease. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source] Histological Characterization of the Thyroglossal Tract: Implications for Surgical Management,THE LARYNGOSCOPE, Issue 6 2001Rakesh K. Chandra MD Abstract Objectives In the current report, we characterized the relationship between the central hyoid bone and the thyroglossal tract and determined the prevalence of ectopic thyroid follicles in the adjacent soft tissues. Study Design Retrospective pathological analysis. Methods The resected specimens from 104 patients who underwent a modified Sistrunk procedure with wide-field dissection were retrospectively analyzed. Under light microscopy, serial sections were examined to determine whether the thyroglossal tract passed anterior to, posterior to, or within the hyoid bone. Specimens were also examined for the presence of thyroid follicles in the periductal and pericystic soft tissues. Results In 50 cases (48%), the tract position in relation to the hyoid bone could not be identified secondary to extensive arborization, marked inflammation, specimen fragmentation or a combination of these. Thyroid follicles were observed in 9 (18%) of these specimens. In the remaining 54 cases (52%) the tract was located anterior to the central arch of the hyoid bone in 39 (72%) and posterior to it in 15 (28%). Thyroid tissue was observed in 46% of specimens (P = .004), regardless of whether the tract was anterior or posterior. Conclusions These results demonstrate that tract position often cannot be defined, but when a portion is dominant, it is likely to be anterior to the hyoid bone. Ectopic thyroid tissue can be found in almost 50% of specimens when the tract position is identifiable. With appropriate surgical management, a recurrence rate of less than 4% can be expected, despite the presence of ductule multiplicity, marked inflammation, tract position posterior to the hyoid bone, and ectopic thyroid follicles. [source] Visceral Leishmaniasis in a Kidney Transplant Recipient: Parasitic Interstitial Nephritis, a Cause of Renal DysfunctionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010S. Dettwiler Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports. In the 61 cases of renal transplant recipients with VL reported in the literature, renal dysfunction was noted at clinical presentation and was more frequently observed as a complication of antiparasitic therapy. However, no pathological analysis of the allograft lesions was reported. We present the case of a Swiss renal transplant recipient who developed VL after vacations in Spain and Tunisia, complicated by acute parasitic nephritis in the renal allograft 3 months after a well-conducted treatment of liposomal amphotericin B. [source] The adjunctive use of power Doppler imaging in the preoperative assessment of prostate cancerBJU INTERNATIONAL, Issue 9 2010Michael L. Eisenberg Study Type , Diagnostic (exploratory cohort) Level of Evidence 2b OBJECTIVE To determine if the adjunctive use of power Doppler imaging (PDI) could provide prognostic utility in the treatment of prostate cancer, as an accurate prediction of the clinical behaviour of prostate cancer is important to determine appropriate treatment. PATIENTS AND METHODS Most centres rely on a digital rectal examination or transrectal ultrasonography (TRUS) to assess the clinical stage of patients. In 2002, we began using a standardized form to evaluate TRUS findings and PDI findings. We compared preoperative clinical findings with those from pathological analysis of 620 radical prostatectomy specimens from 2002 to 2007. RESULTS The mean (sd) patient age was 58 (6.6) years with a mean prostate-specific antigen (PSA) level of 7.0 (4.5) ng/mL. Of the 620 specimens 157 (25.3%) had evidence of extracapsular extension on pathological evaluation; 443 (71.5%) men had a hypervascular lesion seen on TRUS, while 177 (28.5%) patients had none. There was no difference in preoperative PSA level, grade or stage of tumour. Furthermore, rates of biochemical recurrence or secondary treatment did not differ based on PDI findings. As a tool to help locate prostate tumours, PDI improved the specificity of TRUS but did not improve the overall accuracy or sensitivity. CONCLUSION PDI provides little prognostic utility to assess risk in prostate cancer. However, PDI might improve the specificity of TRUS in identifying prostate tumours and could have a role in image guidance for focal therapy of prostate cancer. [source] | ||||||||||