427 resultados para MEDULLA-OBLONGATA


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A 51-year-old Chinese man presented with gaze-evoked nystagmus, impaired smooth pursuit and vestibular ocular reflex cancellation, and saccadic dysmetria, along with a family history suggestive of late-onset autosomal dominant parkinsonism. MRI revealed abnormalities of the medulla and cervical spinal cord typical of adult-onset Alexander disease, and genetic testing showed homozygosity for the p.D295N polymorphic allele in the gene encoding the glial fibrillary acidic protein. A review of the literature shows that ocular signs are frequent in adult-onset Alexander disease, most commonly gaze-evoked nystagmus, pendular nystagmus, and/or oculopalatal myoclonus, and less commonly ptosis, miosis, and saccadic dysmetria. These signs are consistent with the propensity of adult-onset Alexander disease to cause medullary abnormalities on neuroimaging.

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AIM: To investigate the expression of E-cadherin, a major host cell receptor for Listeria monocytogenes (LM) internalin A, in the ruminant nervous system and its putative role in brainstem invasion and intracerebral spread of LM in the natural disease. METHODS: Immunohistochemistry and double immunofluorescence was performed on brains, cranial nerves and ganglia of ruminants with and without natural LM rhombencephalitis using antibodies against E-cadherin, protein gene product 9.5, myelin-associated glycoprotein and LM. RESULTS: In the ruminant brain, E-cadherin is expressed in choroid plexus epithelium, meningothelium and restricted neuropil areas of the medulla, but not in the endothelium. In cranial nerves and ganglia, E-cadherin is expressed in satellite cells and myelinating Schwann cells. Expression does not differ between ruminants with or without listeriosis and does not overlap with the presence of microabscesses in the medulla. LM is observed in phagocytes, axons, Schwann cells, satellite cells and ganglionic neurones. CONCLUSION: Our results support the view that the specific ligand-receptor interaction between LM and host E-cadherin is involved in the neuropathogenesis of ruminant listeriosis. They suggest that oral epithelium and Schwann cells expressing E-cadherin provide a port of entry for free bacteria offering a site of primary intracellular replication, from where the bacterium may invade the axonal compartment by cell-to-cell spread. As E-cadherin expression in the ruminant central nervous system is weak, only very locally restricted and not related to the presence of microabscesses, it is likely that further intracerebral spread is independent of E-cadherin and relies primarily on axonal spread.

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We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, catecholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion.

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PURPOSE: To prospectively evaluate feasibility and reproducibility of diffusion-weighted (DW) and blood oxygenation level-dependent (BOLD) magnetic resonance (MR) imaging in patients with renal allografts, as compared with these features in healthy volunteers with native kidneys. MATERIALS AND METHODS: The local ethics committee approved the study protocol; patients provided written informed consent. Fifteen patients with a renal allograft and in stable condition (nine men, six women; age range, 20-67 years) and 15 age- and sex-matched healthy volunteers underwent DW and BOLD MR imaging. Seven patients with renal allografts were examined twice to assess reproducibility of results. DW MR imaging yielded a total apparent diffusion coefficient including diffusion and microperfusion (ADC(tot)), as well as an ADC reflecting predominantly pure diffusion (ADC(D)) and the perfusion fraction. R2* of BOLD MR imaging enabled the estimation of renal oxygenation. Statistical analysis was performed, and analysis of variance was used for repeated measurements. Coefficients of variation between and within subjects were calculated to assess reproducibility. RESULTS: In patients, ADC(tot), ADC(D), and perfusion fraction were similar in the cortex and medulla. In volunteers, values in the medulla were similar to those in the cortex and medulla of patients; however, values in the cortex were higher than those in the medulla (P < .05). Medullary R2* was higher than cortical R2* in patients (12.9 sec(-1) +/- 2.1 [standard deviation] vs 11.0 sec(-1) +/- 0.6, P < .007) and volunteers (15.3 sec(-1) +/- 1.1 vs 11.5 sec(-1) +/- 0.5, P < .0001). However, medullary R2* was lower in patients than in volunteers (P < .004). Increased medullary R2* was paralleled by decreased diffusion in patients with allografts. A low coefficient of variation in the cortex and medulla within subjects was obtained for ADC(tot), ADC(D), and R2* (<5.2%), while coefficient of variation within subjects was higher for perfusion fraction (medulla, 15.1%; cortex, 8.6%). Diffusion and perfusion indexes correlated significantly with serum creatinine concentrations. CONCLUSION: DW and BOLD MR imaging are feasible and reproducible in patients with renal allografts.

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Hypoxia of renal medulla is a key factor implicated in the development of drug-induced renal failure. Drugs are known to influence renal hemodynamics and, subsequently, affect renal tissue oxygenation. Changes in renal oxygenation can be assessed non-invasively in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI). This study was designed to test the acute effects of administration of specific drugs in healthy human kidney oxygenation using BOLD-MRI. Acute changes in renal tissue oxygenation induced by the non-steroidal anti-inflammatory drug indomethacin, the iodinated radio-contrast media (RCM) iopromidum, and the calcineurin inhibitors cyclosporine micro-emulsion (CsA-ME) and tracrolimus were studied in 30 healthy volunteers. A modified Multi Echo Data Image Combination sequence was used to acquire 12 T(2)(*)-weighted images. Four coronal slices were selected to cover both kidneys. The mean R(2)(*) (1/T(2)(*)) values determined in medulla and cortex showed no significant changes induced by indomethacin and tacrolimus administration. CsA-ME decreased medullary (P=0.008) and cortical (P=0.004) R(2)(*) values 2 h after ingestion. Iopromidum caused a significant increase in medullary R(2)(*) within the first 20 min after injection (P<0.001), whereas no relevant changes were observed in renal cortex. None of the measurements showed left-right kidney differences. Significant differences in renal medullary oxygenation were evidenced between female and male subjects (P=0.013). BOLD-MRI was efficient to show effects of specific drugs in healthy renal tissue. Cyclosporine increased renal medullary oxygenation 2 h after ingestion of a single dose, whereas indomethacin and tacrolimus showed no effect on renal oxygenation. Injection of iodinated RCM decreased renal medullary oxygenation.

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Blood oxygenation level-dependent (BOLD) MRI was shown to allow non-invasive observation of renal oxygenation in humans. However, clinical applications of this type of functional MRI of the kidney are still limited, most likely because of difficulties in obtaining reproducible and reliable information. The aim of this study was to evaluate the reproducibility and robustness of a BOLD method applied to the kidneys and to identify systematic physiological changes potentially influencing the renal oxygenation of healthy volunteers. To measure the BOLD effect, a modified multi-echo data image combination (MEDIC) sequence was used to acquire 12 T2*-weighted images within a single breath-hold. Three identical measurements were performed on three axial and three coronal slices of right and left kidneys in 18 volunteers. The mean R2* (1/T2*) values determined in medulla and cortex showed no significant differences over three repetitions and low intra-subject coefficients of variation (CV) (3 and 4% in medulla and cortex, respectively). The average R2* values were higher in the medulla (16.15 +/- 0.11) than in the cortex (11.69 +/- 0.18) (P < 0.001). Only a minor influence of slice orientation was observed. Mean R2* values were slightly higher (3%) in the left than in the right kidney (P < 0.001). Differences between volunteers were identified (P < 0.001). Part of these differences was attributable to age-dependent R2* values, since these values increased with age when medulla (P < 0.001, r = 0.67) or cortex (P < 0.020, r = 0.42) were considered. Thus, BOLD measurements in the kidney are highly reproducible and robust. The results allow one to identify the known cortico-medullary gradient of oxygenation evidenced by the gradient of R2* values and suggest that medulla is more hypoxic in older than younger individuals. BOLD-MRI is therefore a useful tool to study sequentially and non-invasively regional oxygenation of human kidneys.

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Carotid sinus baroreceptors are involved in controlling blood pressure (BP) by providing input to the cardiovascular regulatory centers of the medulla. The acute effect of temporarily placing an electrode on the carotid sinus wall to electrically activate the baroreflex was investigated. We studied 11 patients undergoing elective carotid surgery. Baseline BP was 146+30/66+/-17 mm Hg and heart rate (HR) 72+/-7 bpm (mean +/- standard deviation). An electrode was placed upon the carotid sinus and after obtaining a steady state baseline of BP and HR, an electric current was applied and increased in 1-volt increments. A voltage dependent and highly significant reduction in BP was observed which averaged 18+/-26* and 8.0+/-12 mm Hg for systolic BP and diastolic BP, respectively. Maximal reductions occurred at 4.4+/-1.2 V: 23+/-24 mm Hg*, 16+/-10 mm Hg* and 7+/-12 bpm* for systolic BP, diastolic BP and HR, respectively ( = p <.05). Thus, electrical stimulation of the carotid sinus activates the carotid baroreflex resulting in a reduction in BP and HR. This presents a proof of concept for device based baroreflex modulation in acute BP regulation and adds to the available data which provide a rationale for evaluating this system in the context of chronic BP reduction in hypertensive patients.

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Neuropeptide Y (NPY), which is found in high concentrations in several regions of the brain including nuclei of the brain stem and in nerve fibers surrounding cerebral vessels, has been proposed to play a role in regulating cerebral blood flow (CBF) and systemic vegetative functions. Since CBF is altered during meningitis, we examined whether NPY concentrations changed in various regions of the rabbit brain in response to experimental pneumococcal meningitis. Changes were most pronounced in the medulla, where NPY concentration increased threefold after 48 h of infection. Concomitantly, there was an increase in NPY immunoreactive fibers surrounding small vessels in the dorsolateral medulla, especially in the nucleus tractus solitarius. These results suggest that NPY may play a role in inducing some of the hemodynamic changes seen during pneumococcal meningitis.

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PURPOSE: To prospectively determine if changes in intrarenal oxygenation during acute unilateral ureteral obstruction can be depicted with blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved by the local ethics committee, and written informed consent was obtained from all patients. BOLD MR imaging was performed in 10 male patients (mean age, 45 years +/- 17 [standard deviation]; range, 20-73 years) with a distal unilateral ureteral calculus and in 10 healthy age-matched male volunteers to estimate R2*, which is inversely related to tissue Po(2). R2* values were determined in the cortex and medulla of the obstructed and the contralateral nonobstructed kidneys. To reduce external effects on R2*, the R2* ratio between the medulla and cortex was also analyzed. Statistical analysis was performed with nonparametric rank tests. P < .05 was considered to indicate a significant difference. RESULTS: All patients had significantly lower medullary and cortical R2* values in the obstructed kidney (median R2* in medulla, 10.9 sec(-1) [range, 9.1-14.3 sec(-1)]; median R2* in cortex, 10.4 sec(-1) [range, 9.7-11.3 sec(-1)]) than in the nonobstructed kidney (median R2* in medulla, 17.2 sec(-1) [range, 14.6-23.2 sec(-1)], P = .005; median R2* in cortex, 11.7 sec(-1) [range, 11.0-14.0 sec(-1)], P = .005); values in the obstructed kidneys were also significantly lower than values in the kidneys of healthy control subjects (median R2* in medulla, 16.1 sec(-1) [range, 13.9-18.1 sec(-1)], P < .001; median R2* in cortex, 11.6 sec(-1) [range, 10.5-12.9 sec(-1)], P < .001). R2* ratios in the obstructed kidneys (median, 1.06; range, 0.85-1.27) were significantly lower than those in the nonobstructed kidneys (median, 1.49; range, 1.26-1.71; P = .005) and those in the kidneys of healthy control subjects (median, 1.38; range, 1.23-1.47; P < .001). In contrast, R2* ratios in the nonobstructed kidneys of patients were significantly higher than those in kidneys of healthy control subjects (P = .01). CONCLUSION: Increased oxygen content in the renal cortex and medulla occurs with acute unilateral ureteral obstruction, suggesting reduced function of the affected kidney.

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RATIONALE AND OBJECTIVES: A feasibility study on measuring kidney perfusion by a contrast-free magnetic resonance (MR) imaging technique is presented. MATERIALS AND METHODS: A flow-sensitive alternating inversion recovery (FAIR) prepared true fast imaging with steady-state precession (TrueFISP) arterial spin labeling sequence was used on a 3.0-T MR-scanner. The basis for quantification is a two-compartment exchange model proposed by Parkes that corrects for diverse assumptions in single-compartment standard models. RESULTS: Eleven healthy volunteers (mean age, 42.3 years; range 24-55) were examined. The calculated mean renal blood flow values for the exchange model (109 +/- 5 [medulla] and 245 +/- 11 [cortex] ml/min - 100 g) are in good agreement with the literature. Most important, the two-compartment exchange model exhibits a stabilizing effect on the evaluation of perfusion values if the finite permeability of the vessel wall and the venous outflow (fast solution) are considered: the values for the one-compartment standard model were 93 +/- 18 (medulla) and 208 +/- 37 (cortex) ml/min - 100 g. CONCLUSION: This improvement will increase the accuracy of contrast-free imaging of kidney perfusion in treatment renovascular disease.

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Inhibitors of angiogenesis and radiation induce compensatory changes in the tumor vasculature both during and after treatment cessation. To assess the responses to irradiation and vascular endothelial growth factor-receptor tyrosine kinase inhibition (by the vascular endothelial growth factor tyrosine kinase inhibitor PTK787/ZK222854), mammary carcinoma allografts were investigated by vascular casting; electron, light, and confocal microscopy; and immunoblotting. Irradiation and anti-angiogenic therapy had similar effects on the tumor vasculature. Both treatments reduced tumor vascularization, particularly in the tumor medulla. After cessation of therapy, the tumor vasculature expanded predominantly by intussusception with a plexus composed of enlarged sinusoidal-like vessels containing multiple transluminal tissue pillars. Tumor revascularization originated from preserved alpha-smooth muscle actin-positive vessels in the tumor cortex. Quantification revealed that recovery was characterized by an angiogenic switch from sprouting to intussusception. Up-regulated alpha-smooth muscle actin-expression during recovery reflected the recruitment of alpha-smooth muscle actin-positive cells for intussusception as part of the angio-adaptive mechanism. Tumor recovery was associated with a dramatic decrease (by 30% to 40%) in the intratumoral microvascular density, probably as a result of intussusceptive pruning and, surprisingly, with only a minimal reduction of the total microvascular (exchange) area. Therefore, the vascular supply to the tumor was not severely compromised, as demonstrated by hypoxia-inducible factor-1alpha expression. Both irradiation and anti-angiogenic therapy cause a switch from sprouting to intussusceptive angiogenesis, representing an escape mechanism and accounting for the development of resistance, as well as rapid recovery, after cessation of therapy.

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PURPOSE: To prospectively assess the potential of noninvasive diffusion-weighted magnetic resonance (MR) imaging to depict changes in microperfusion and diffusion in patients with acute unilateral ureteral obstruction. MATERIALS AND METHODS: The local ethics committee approved the study protocol. Informed consent was obtained. Diffusion-weighted MR imaging was performed in 21 patients (two women, 19 men; mean age, 43 years +/- 10 [standard deviation]) with acute unilateral ureteral obstruction due to a calculus diagnosed at unenhanced computed tomography. A control group (one woman, 15 men; mean age, 44 years +/- 12) underwent the same MR protocol. Standard processing yielded an apparent diffusion coefficient (ADC) ADCT; the separation of microperfusion and diffusion contributions yielded the perfusion fraction FP and the pure diffusion coefficient ADCD. ADCT, ADCD, and FP were compared between obstructed and contralateral unobstructed kidneys and with control values. For statistical analysis, nonparametric rank tests were used. A P value of less than .05 was considered significant. RESULTS: No significant differences were observed between the ADCT of the medulla or cortex of the obstructed and unobstructed kidneys. Compared with control kidneys, only medullary ADCT was slightly increased in the obstructed kidney (P < .04). However, the ADCD in the medulla of the obstructed and unobstructed kidneys was significantly higher than that in control subjects (201 x 10(-5) mm2/sec +/- 16 and 199 x 10(-5) mm2/sec +/- 20 vs 189 x 10(-5) mm2/sec +/- 12; P < .008 and P < .03, respectively). FP of the cortex of the obstructed kidney was significantly lower than that in the unobstructed kidney (20.2% +/- 4.8 vs 24.0% +/- 5.8; P < .002); FP of the medulla was slightly lower in the obstructed kidney than in the unobstructed kidney (18.3% +/- 5.9 vs 20.7% +/- 6.4; P = .05). CONCLUSION: Diffusion-weighted MR imaging allows noninvasive detection of changes in renal perfusion and diffusion during acute unilateral ureteral obstruction, as exemplified in patients with a ureteral calculus.

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BACKGROUND Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). METHODS Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. RESULTS The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. CONCLUSION This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

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Purpose To determine whether diffusion-weighted (DW) magnetic resonance (MR) imaging in living renal allograft donation allows monitoring of potential changes in the nontransplanted remaining kidney of the donor because of unilateral nephrectomy and changes in the transplanted kidney before and after transplantation in donor and recipient, respectively, and whether DW MR parameters are correlated in the same kidney before and after transplantation. Materials and Methods The study protocol was approved by the local ethics committee; written informed consent was obtained. Thirteen healthy kidney donors and their corresponding recipients prospectively underwent DW MR imaging (multiple b values) in donors before donation and in donors and recipients at day 8 and months 3 and 12 after donation. Total apparent diffusion coefficient (ADCT) values were determined; contribution of microcirculation was quantified in perfusion fraction (FP). Longitudinal changes of diffusion parameters were compared (repeated-measures one-way analysis of variance with post hoc pairwise comparisons). Correlations were tested (linear regression). Results ADCT values in nontransplanted kidney of donors increased from a preexplantation value of (188 ± 9 [standard deviation]) to (202 ± 11) × 10(-5) mm(2)/sec in medulla and from (199 ± 11) to (210 ± 13) × 10(-5) mm(2)/sec in cortex 1 week after donation (P < .004). Medullary, but not cortical, ADCT values stayed increased up to 1 year. ADCT values in allografts in recipients were stable. Compared with values obtained before transplantation in donors, the corticomedullary difference was reduced in allografts (P < .03). Cortical ADCT values correlated with estimated glomerular filtration rate in recipients (R = 0.56, P < .001) but not donors. Cortical ADCT values in the same kidney before transplantation in donors correlated with those in recipients on day 8 after transplantation (R = 0.77, P = .006). FP did not show significant changes. Conclusion DW MR imaging depicts early adaptations in the remaining nontransplanted kidney of donors after nephrectomy. All diffusion parameters remained constant in allograft recipients after transplantation. This method has potential monitoring utility, although assessment of clinical relevance is needed. © RSNA, 2013 Online supplemental material is available for this article.

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PURPOSE Little data is available on noninvasive MRI-based assessment of renal function during upper urinary tract (UUT) obstruction. In this study, we determined whether functional multiparametric kidney MRI is able to monitor treatment response in acute unilateral UUT obstruction. MATERIAL AND METHODS Between 01/2008 and 01/2010, 18 patients with acute unilateral UUT obstruction due to calculi were prospectively enrolled to undergo kidney MRI with conventional, blood oxygen level-dependent (BOLD) and diffusion-weighted (DW) sequences on emergency admission and after release of obstruction. Functional imaging parameters of the obstructed and contralateral unobstructed kidneys derived from BOLD (apparent spin relaxation rate [R2*]) and DW (total apparent diffusion coefficient [ADCT], pure diffusion coefficient [ADCD] and perfusion fraction [FP]) sequences were assessed during acute UUT obstruction and after its release. RESULTS During acute obstruction, R2* and FP values were lower in the cortex (p=0.020 and p=0.031, respectively) and medulla (p=0.012 and p=0.190, respectively) of the obstructed compared to the contralateral unobstructed kidneys. After release of obstruction, R2* and FP values increased both in the cortex (p=0.016 and p=0.004, respectively) and medulla (p=0.071 and p=0.044, respectively) of the formerly obstructed kidneys to values similar to those found in the contralateral kidneys. ADCT and ADCD values did not significantly differ between obstructed and contralateral unobstructed kidneys during or after obstruction. CONCLUSIONS In our patients with acute unilateral UUT obstruction due to calculi, functional kidney MRI using BOLD and DW sequences allowed for the monitoring of pathophysiologic changes of obstructed kidneys during obstruction and after its release.