Tissue factor pathway inhibitor expression in human crescentic glomerulonephritis.
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BACKGROUND: Tissue factor (TF) pathway inhibitor (TFPI), the major endogenous inhibitor of extrinsic coagulation pathway activation, protects renal function in experimental crescentic glomerulonephritis (GN). Its glomerular expression and relationship to TF expression and fibrin deposition in human crescentic GN have not been reported. METHODS: Glomerular TFPI, TF, and fibrin-related antigen (FRA) expression were correlated in renal biopsies from 11 patients with crescentic GN. Biopsies from 11 patients with thin basement membrane disease and two normal kidneys were used as controls. RESULTS: TFPI was undetectable in control glomeruli but was detectable in interstitial microvessels. In crescentic biopsies, TFPI was detected in cellular crescents and was more prominent in fibrous/fibrocellular crescents, indicating a correlation with the chronicity of crescentic lesions. TFPI appeared to be associated with macrophages but not endothelial or epithelial cells. TFPI was generally undetectable in regions of the glomerular tuft with minimal damage. In contrast, TF and FRA were strongly expressed in regions of minimal injury, as well as in more advanced proliferative and necrotizing lesions. Despite prominent TF expression, FRA was less prominent in fibrous/fibrocellular crescents in which TFPI expression was maximal. CONCLUSIONS: These data suggest that TFPI is strongly expressed in the later stages of crescent formation and is inversely correlated with the presence of FRA in human crescentic GN. This late induction of TFPI may inhibit TF activity and favor reduced fibrin deposition in the chronic stages of crescent formation. (+info)
Proton magnetic resonance spectroscopy pattern of progressive multifocal leukoencephalopathy in AIDS.
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The objective was to determine whether the use of intermediate echo times (135 ms) in proton magnetic resonance spectroscopy (1H-MRS) detects a homogenous pattern in progressive multifocal leukoencephalopathy (PML) in HIV-1 infected people, and to confirm the results of previous studies. Six patients infected with HIV-1, with PML established by biopsy, and six healthy age and sex matched volunteers were evaluated to define their spectroscopic pattern. 1H-MRS spectra performed at 1.5 T were obtained with the STEAM sequence: TE/TM/TR, 20 ms/13.7 ms/2000 ms; 2500 Hz, size 2048 points, 256 acquisitions (STEAM-20) and with the PRESS sequence; TE/TR, 135 ms/2000 ms; 2500 Hz, size 2048 points, 256 acquisitions (PRESS-135). A single voxel was placed on the lesions and on the parieto-occipital white matter of controls. The peaks of N-acetylaspartate (NAA), choline (Cho), myoinositol (mI), lactate, and lipids were considered, and the results were expressed using creatine as reference. Spectra of PML lesions were characterised by significantly reduced NAA, lactate presence, and by significantly increased Cho and lipids compared with control group values. These results indicate that 1H-MRS detects a homogenous pattern in PML lesions. Recent studies, together with this, suggest that 1H-MRS may help in the diagnostic approach to patients with suspected PML lesions associated with AIDS. (+info)
Whipple's disease mimicking progressive supranuclear palsy: the diagnostic value of eye movement recording.
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Treatable causes of parkinsonian syndromes are rare; Whipple's disease is one of them. A patient is described who presented with a parkinsonian syndrome and abnormal vertical gaze. Measurement of eye movements showed marked slowing of upward saccades, moderate slowing of downward saccades, a full range of voluntary vertical eye movements, curved trajectories of oblique saccades, and absence of square wave jerks. These features, atypical of progressive supranuclear palsy, suggested the diagnosis of Whipple's disease, which was subsequently confirmed by polymerase chain reaction analysis of intestinal biopsy material. Precise measurement of the dynamic properties of saccadic eye movements in parkinsonian patients may provide a means of identifying treatable disorders. (+info)
Fas expression and apoptosis correlate with cardiac dysfunction in patients with dilated cardiomyopathy.
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Fas is a transmembranous glycoprotein that mediates apoptosis. To elucidate the roles of Fas and of myocyte apoptosis in patients with dilated cardiomyopathy (DCM), the expression of Fas and the fragmentation of DNA were compared in endomyocardial biopsy specimens obtained from patients with DCM. Endomyocardial biopsy was performed on 19 subjects (16 with DCM and 3 control subjects) who also underwent cardiac catheterization and echocardiography. Fas and bcl-2 expression were assayed immunohistochemically, and in situ TdT staining was performed to estimate the number of apoptotic cells. Samples from the DCM patients stained more intensely with anti-Fas antibody than those from control patients (p<0.05). The percentage of in situ TdT-positive cells was significantly higher in the DCM group than in the control group (p<0.05). A correlation between Fas expression and in situ TdT staining was observed in 67% of myocytes in the DCM group. Moreover, the percentage of in situ TdT staining was significantly higher in subjects with severely impaired left ventricular systolic function than in those whose systolic function was mild to moderately impaired, or who had normal systolic function (p<0.05). The samples showed little expression of bcl-2. These results suggest that Fas expression and apoptosis may be involved in the progression of cardiac dysfunction in DCM. (+info)
Lessons learned from 500 cases of lymphatic mapping for breast cancer.
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OBJECTIVE: To evaluate the factors affecting the identification and accuracy of the sentinel node in breast cancer in a single institutional experience. SUMMARY BACKGROUND DATA: Few of the many published feasibility studies of lymphatic mapping for breast cancer have adequate numbers to assess in detail the factors affecting failed and falsely negative mapping procedures. METHODS: Five hundred consecutive sentinel lymph node biopsies were performed using isosulfan blue dye and technetium-labeled sulfur colloid. A planned conventional axillary dissection was performed in 104 cases. RESULTS: Sentinel nodes were identified in 458 of 492 (92%) evaluable cases. The mean number of sentinel nodes removed was 2.1. The sentinel node was successfully identified by blue dye in 80% (393/492), by isotope in 85% (419/492), and by the combination of blue dye and isotope in 93% (458/492) of patients. Success in locating the sentinel node was unrelated to tumor size, type, location, or multicentricity; the presence of lymphovascular invasion; histologic or nuclear grade; or a previous surgical biopsy. The false-negative rate of 10.6% (5/47) was calculated using only those 104 cases where a conventional axillary dissection was planned before surgery. CONCLUSIONS: Sentinel node biopsy in patients with early breast cancer is a safe and effective alternative to routine axillary dissection for patients with negative nodes. Because of a small but definite rate of false-negative results, this procedure is most valuable in patients with a low risk of axillary nodal metastases. Both blue dye and radioisotope should be used to maximize the yield and accuracy of successful localizations. (+info)
Independent evaluation of onchocerciasis rapid assessment methods in Benue State, Nigeria.
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OBJECTIVE: To evaluate the prevalence of palpable nodules or skin depigmentation as rapid indicators of onchocerciasis epidemicity in at-risk communities. METHOD: We examined data collected in Benue State on 11035 individuals in 32 villages to evaluate these rapid assessment methods. RESULTS: The prevalence of palpable nodules correlates more closely with microfilarial prevalence (r=0.68, P<0.001) and community microfilarial load (r=0.64, P<0.001) than the prevalences of skin depigmentation or other potential rapid indicators. The recommended cut-off value for palpable nodules of 20% or more in males aged >20 years had a sensitivity of 94% and specificity of 50% compared to a cut-off of 40% or more for microfilarial prevalence in all ages. This would mean that in these 32 villages 17 of 18 would have been correctly identified for treatment, and a further 7 at lesser risk would have been targeted for treatment. CONCLUSIONS: Skin snipping and parasitological examination can be replaced by the simpler method of palpating onchocercal nodules to identify communities at serious risk of onchocerciasis. This has important operational benefits for onchocerciasis control programmes. (+info)
The myocardial profile of the cytosolic isozymes of creatine kinase is apparently not related to cyanosis in congenital heart disease.
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BACKGROUND: CKMB, the cardiac-specific heterodimer of cytosolic creatine-kinase (CK), is developmentally and physiologically regulated, tissue hypoxia being a proposed regulator. In patients with cyanotic heart disease the myocardium is perfused with partially saturated blood. We questioned whether the myocardium of cyanotic subjects contains higher proportions of CKMB. MATERIALS AND METHODS: CK activity, the distribution of cytosolic CK isozymes, activity of lactic dehydrogenase (LDH), and tissue protein content were determined in obstructive tissues removed at corrective surgery of patients with congenital heart defects. Cyanotic (n = 13) and acyanotic (n = 12) subjects were compared. RESULTS: In cyanotic and acyanotic patients, CK activity was 8.4 +/- 0.6 and 7.6 +/- 0.6 IU/mg protein and the proportion of CKMB was 21 +/- 1.4 and 22 +/- 2. 0% (mean +/- S.E.M), respectively. In the two groups of patients, the activity related to the B subunit corresponded to the steady-state level of the CKBmRNA. The tissue content of protein and the activities of CK and LDH were similar in cyanotic and acyanotic subjects and increased with the age. CONCLUSIONS: The lack of difference in CKMB distribution between the cyanotic and acyanotic patients may either indicate that hypooxygenation is not a regulator of CK isozyme expression, or may be attributed to the already high proportion of this isozyme in hypertrophied, obstructive tissues. Recruitment of additional CKMB, in the cyanotic hearts, may thus not be required. (+info)
Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa.
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BACKGROUND: The beta chemokine monocyte chemotactic protein 3 (MCP-3) has chemoattractant and activating capabilities in monocytes, lymphocytes, eosinophils, and basophils. AIMS: To investigate MCP-3 expression in inflammatory conditions of the human intestinal mucosa. PATIENTS: Forty five colon biopsy specimens from 18 patients with inflammatory bowel disease (IBD; 16 specimens from inflamed and 10 from non-inflamed areas) and 19 control patients were examined. METHODS: Immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) were used for MCP-3 detection in tissue sections. Intestinal epithelial cell lines (HT-29, Caco-2, T-84) were stimulated with interleukin (IL) 1beta, IL-6, and tumour necrosis factor alpha (TNF-alpha) and examined for MCP-3 protein and mRNA expression using immunocytochemistry and RT-PCR, respectively. RESULTS: In tissue sections, MCP-3 protein was detected predominantly in epithelial cells, both in patients with IBD and in controls. MCP-3 staining was particularly pronounced at sites of active mucosal inflammation. The intensity of MCP-3 staining was positively correlated with the extent of epithelial destruction. In intestinal epithelial cell lines, MCP-3 mRNA was expressed, whereas MCP-3 protein was not consistently detected. CONCLUSIONS: Our data show that MCP-3 protein is present in normal and inflamed intestinal tissue. MCP-3 production is substantially enhanced in areas of active inflammation, suggesting an immunoregulatory role of MCP-3 in intestinal inflammation. (+info)