[Hypercalcemia: etiology, diagnosis, treatment].
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Adenoma↗
Biomedical subjects
M Essig
Publications and source records attributed to M Essig.
Uterine cervical carcinoma: comparison of standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival.
Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as for therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this study to: (a) examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis [microvessel density (MVD) and vascular endothelial growth factor (VEGF)]; and (b) determine the ultimate value of a histomorphological and a dynamic MRI approach by the correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) and standard parameters [the maximum signal intensity increase over baseline (SI-I) and the steepest signal intensity-upslope per second (SI-U/s)] were calculated from a contrast-enhanced dynamic MRI series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD and VEGF) were compared to MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found between MVD and A (P < 0.01) and SI-I (P < 0.05). No significant relationships were observed between VEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based on k21 and SI-U/s showed that tumors with high k21 and SI-U/s values had a significantly (P < 0.05 and 0.001, respectively) worse disease outcome than did tumors with low k21 and SI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD and VEGF) had any significant power to predict patient survival. It is concluded that in patients with uterine cervical cancer: (a) the pathophysiological basis for differences in dynamic MRI is MVD but not VEGF expression; (b) a functional, dynamic MRI approach (both standard and pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than are the current histomorphological-based markers of tumor angiogenesis; and (c) compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assess MVD or patient survival.
Contrast Media↗
[Regulation of phosphatemia and hypophosphatemia].
Phosphate is an essential element for cellular metabolism and bone mineralization. The kidney regulates phosphate homeostasis by modulating the proximal reabsorption of phosphate. This regulation is mediated by hormonal or autocrine/paracrine factors. Recent results concerning the molecular structure of phosphate transport systems have clarified the mechanisms underlying the effects of these mediators. Hypophosphatemia is a frequent biological finding which results either from an intracellular shift of phosphate, or from a defect in the intestinal absorption or a renal leak. The decrease in phosphate leads to a depletion in cellular ATP (which accounts for neurological and muscular symptoms), to bone demineralization and to renal lithiasis when a renal leak exists.
Absorption↗
Corpus callosum in Alzheimer's disease and vascular dementia--a quantitative magnetic resonance study.
We investigated atrophic alterations in different regions of the corpus callosum in Alzheimer's disease (AD) and vascular dementia (VD) with respect to clinical changes. 32 patients with AD (NINCDS-ADRDA criteria), 17 patients with VD (NINDS-AIREN criteria) and 13 healthy control subjects were included. 3-D MRI sequences were acquired using a 1.5T MRI scanner. The size of the corpus callosum and its subdivisions was sampled on 5 mid-saggital slices using a personal computer-based software. Total callosal size was significantly reduced in AD but not in VD. Furthermore, the most rostral parts of the corpus callosum were significantly smaller in AD when compared to controls. Again, these changes were not found in patients with VD. Severity of dementia was significantly correlated with the size of the midbody of the corpus callosum in AD. Callosal atrophy in AD may reflect the severity and pattern of cortical neuronal damage occurring mostly in the inferior frontal, anterior parietal and midtemporal regions. Correlations between regional callosal atrophy and severity of dementia indicate that interhemispheric cortico-cortical disconnections may contribute to the dementia syndrome.
Aged↗
High-resolution venography of the brain using magnetic resonance imaging.
The purpose of this study was to evaluate a non-flow related magnetic resonance imaging method to visualize small veins independent of arteries in the human brain. A long TE, high-resolution 3D gradient echo MR acquisition was used to highlight venous information. The method is based on the paramagnetic property of deoxyhemoglobin and the resulting phase difference between veins and brain parenchyma at long echo times. The MR magnitude images were masked with a phase mask filter to enhance small structure visibility. Venous information down to sub-pixel vessel diameters of several hundred microns is visible. Venous data are displayed in an angiographic manner using a minimum intensity projection algorithm. Both superficial veins and deep white matter veins are visible. The method has been successfully applied in volunteers. Preliminary results in patients with cerebral arteriovenous malformations indicate its potential in clinical applications. The proposed method is easy to implement and does not require administration of a contrast agent or application of specially designed rf pulses to highlight the veins. Rather it exploits the intrinsic magnetic properties (BOLD-effect) and the prolonged T2* of venous blood. The method may be of diagnostic potential in the assessment of arteriovenous malformations or other vascular venous lesions.
Adolescent↗
[Volumetric brain findings in late depression. A study with quantified magnetic resonance tomography].
A number of observations including clinical manifestation, course, outcome, and family history, support the view that patients presenting with a major depression occurring first in late life should be treated as a nosological subgroup. In this study quantitative magnetic resonance imaging (MRI) was used to investigate volumes of different brain structures in 19 patients with late onset major depression (age of onset > 50) and 13 age matched controls. 3-D MRI sequences were acquired using a Siemens 1.5T scanner. Whole brain volume, CSF volume, volume of the frontal and temporal lobes and the volume of the amygdala-hippocampus complex were assessed using the software NMRWin. Compared to the controls, depressed patients showed a significantly lower whole brain volume and a significantly higher CSF volume, whereas volumes of the frontal and temporal lobes as well as the amygdala-hippocampus complex volumes were not significantly decreased. In addition, depressed patients exhibited a higher ventricle-brain ratio suggesting a higher degree of central atrophy compared to healthy individuals. Our results indicate that cerebral changes involving subcortical structures are of relevance in the pathogenesis of late-onset depression. Defining the aetiology of these lesions may be important for the development of preventive treatment of depression in the elderly.
Aged↗
[Angiogenesis of cervix carcinoma. Contrast enhanced dynamic MRI, histologic quantification of capillary density and lymphatic system infiltration].
PURPOSE: It was the aim of this project to examine (i) the relationships between contrast-enhanced dynamic MR imaging derived characteristics and histologic microvessel density counts--a recognized surrogate of tumor angiogenesis--from tumors in patients with primary or recurrent cancer of the uterine cervix, and (ii) to correlate these parameters with lymphatic involvement (i.e. lymphatic channels) to assess tumor biological aggressiveness in terms of lymphatic spread. MATERIAL AND METHODS: Pharmacokinetic MR imaging parameters (amplitude A, exchange rate constant k21) were derived from contrast-enhanced dynamic MR imaging in thirty-three patients with biopsy proven cancer of the uterine cervix. The pharmacokinetic MR imaging characteristics were correlated to histologic capillary density counts obtained from whole mount specimen. In addition, these data were correlated to the angiogenic activity as a marker for lymphatic system involvement. RESULTS: Pharmacokinetic MR imaging derived parameters (A, k21) showed a weak but significant (p < 0.05) correlation with microvessel density counts. Lymphatic involvement was more comprehensively assessed by the pharmacokinetic parameter k21 compared with histologic microvessel density, resulting in a significantly (p < 0.05) higher overall accuracy (85% vs. 64%), sensitivity (83% vs. 54%), and comparable specificity (89% vs. 89%), respectively. CONCLUSION: Our first results show that the signal-time curves measured by contrast-enhanced MR imaging are only in part influenced by microvessel density. In addition, MR imaging derived characteristics may assess tumor biological aggressiveness in terms of lymphatic spread (i.e. lymphatic channels) more comprehensively than histologic microvessel density in patients with primary or recurrent cancer of the uterine cervix.
Adult↗
[MRI imaging of the uterine arterial blood flow in normal and malignant uterine tissue by means of 2d-multiphase tagging technic].
PURPOSE: The aim of this pilot study was to evaluate a 2D-STAR technique as a non contrast-enhanced approach to demonstrate the uterine artery and its branches and to assess the cervical uterine blood flow in healthy volunteers and in patients with advanced uterine cervical carcinoma. MATERIALS AND METHODS: Seven healthy volunteers (mean age, 29 years) and twenty-two patients (mean age, 52 years) with advanced cancer of the uterine cervix (FIGO IIB-IVA) were prospectively examined by 2D-STAR imaging at different inversion delay times (300 ms-1900 ms) which showed the passage of a blood bolus through normal and malignant tissue of the uterine cervix. RESULTS: The uterine artery was well visualized with short inversion delay times of 300 ms to 500 ms. It was characterized as single or multiple helical loops before dividing into its intracervical branches. The intracervical branching was observed at inversion delay times of 500 ms-700 ms. With longer inversion delay times arterial signal enhancement disappeared and cervical tissue enhancement was noted. Enhancement of benign tissue was observed at inversion delay times of 1100 ms-1700 ms, and in malignant tissue at shorter inversion delay times of 900 ms-1300 ms. The maximum of this diffuse signal enhancement of benign tissue was seen at inversion delay times of 1500 ms (1100 ms-1700 ms), in malignant tissue at significantly (P < 0.05) shorter inversion delay times of 1100 ms (900 ms to 1300). CONCLUSION: Our preliminary results show that the vascular supply and blood flow of the normal uterine cervix and of advanced cervical cancer can be assessed by non contrast-enhanced 2D STAR imaging and that malignant cervical tissue is earlier and stronger perfused than normal cervical tissue.
Adult↗
Magnetically labeled water perfusion imaging of the uterine arteries and of normal and malignant cervical tissue: initial experiences.
PURPOSE: The aim of this pilot study was to evaluate a magnetically labeled water perfusion imaging technique as a non-contrast-enhanced approach to demonstrate the uterine artery, its branches, and to assess the cervical uterine blood flow in healthy volunteers and in patients with advanced uterine cervical carcinoma (FIGO IIB-IVA). METHODS AND MATERIALS: Seven healthy volunteers (mean age, 29 years) and twenty-two patients (mean age, 52 years) with advanced cancer of the uterine cervix (FIGO IIB-IVA) were prospectively examined by magnetically labeled water perfusion imaging at different inversion delay times (300-900 ms). The magnetic resonance imaging (MRI) findings of all patients were matched to the findings of contrast-enhanced dynamic MRI and multiple biopsies (n = 5) and/or surgical whole mount specimens (n = 17), which were available in all patients. RESULTS: The uterine artery was well visualized with short inversion delay times of 300-500 ms. It was characterized as single or multiple helical loops before dividing into its intracervical branches. The intracervical branching was observed at inversion delay times of 500-700 ms. With longer inversion delay times, arterial signal enhancement disappeared and cervical tissue enhancement was noted. Enhancement of benign tissue was observed at inversion delay times of 1100-1700 ms and in malignant tissue at shorter inversion delay times of 900-1300 ms. The maximum of this diffuse signal enhancement of benign tissue was seen at inversion delay times of 1500 ms (1100-1700 ms) in malignant tissue at significantly (p < 0.5) shorter inversion delay times of 1100 ms (900-1300 ms). CONCLUSION: Our preliminary results show that the vascular supply and blood flow of the normal uterine cervix and of advanced cervical cancer can be assessed by magnetically labeled water perfusion imaging and that malignant cervical tissue is earlier and stronger perfused than normal cervical tissue.
Adult↗
[Acute ischemic cerebral infarct: prospective serial observations by magnetic resonance imaging].
AIM: Serial observations of acute ischaemic cerebral infarcts by MRI in order to define signal patterns, contrast uptake, oedema and secondary haemorrhage over a period of three months. METHODS: Prospective serial examinations of 34 patients with acute cerebral ischaemia who were examined during the first 48 hours, on days 3 or 4, 7, 14, 21, 28 and after three months by MRI (spin echo TR/TE 2200/100/20, 500/20, +/- Gd). RESULTS: T2 weighted spin echo sequences showed the highest sensitivity (88%) during the first 8 hours of cerebral ischaemia when compared with other spin echo sequences. Parenchymal contrast enhancement showed a distinct peak during the second and third weeks. The use of contrast did not improve diagnosis of an infarct during any stage. 87% of lesions showed haemorrhage at some stage. Vascular enhancement was observed in 25% of infarcts during the first 24 hours and was still present after three months in 20%. Parenchymal and vascular enhancement, and haemorrhage correlate with the size of the infarct. CONCLUSION: Focal cerebral ischaemia produces an abnormality of the blood-brain barrier, oedema and finally necrosis, depending on the severity and duration of the lesion. Haemorrhage in 87% was considerably more common than has been described previously. Vascular enhancement is not an early sign of an infarct, contrary to what has been described in the literature.
Acute Disease↗
[MR tomographic monitoring of prostate carcinoma after cryotherapy: initial results].
PURPOSE: To assess the morphological changes in the prostate gland and adjacent tissue after cryosurgery by high resolution MRI in patients with histological proven prostatic carcinoma. METHOD: 15 patients (mean age 66 years) with histologically proven prostate carcinoma underwent T2- and contrast-enhanced T1-weighted high-resolution MRI examinations with fat suppression. Follow-up MRI with an identical imaging protocol were performed at different time intervals (24-72 h, 2-6, 12, 26-52 weeks). RESULTS: Mean prostate volume had decreased by 30% in all patients 12-52 weeks after cryosurgery. After cryosurgery, zonal differentiation was lost in all patients with abnormalities in the periprostatic tissue in all patients, and rectal wall thickening in 47% of patients. Cryosurgery-induced changes in the prostate could not be differentiated from tumour recurrence. CONCLUSION: High resolution MRI allows precise recognition of intraprostatic and adjacent tissue alterations after cryosurgery of prostatic carcinoma. However, reliable detection of tumour recurrence was impossible due to cryosurgically induced signal changes.
Aged↗
[Detection of angiogenesis-dependent parameters by functional MRI: correlation with histomorphology and evaluation of clinical relevance as prognostic factor using cervix carcinoma as an example].
PURPOSE: Purpose of this study is to compare functional MRI parameters with histomorphological markers of tumor microvessel density (MVD) and permeability (vascular endothelial growth factor) and to determine the ultimate value of both approaches by correlation with disease outcome in patients with primary cancer of the uterine cervix. METHOD: Pharmacokinetic parameters were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the operative whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using logrank statistics. RESULTS: Significant (p < 0.05-0.01) associations were found between MVD and dynamic MRI parameters. No significant relationships were observed between VEGF expression and dynamic MRI parameters. Disease outcome was better assessed with dynamic MRI parameters than with the histomorphological approach. CONCLUSIONS: It is concluded that 1) the pathophysiological basis for the amplitude A in dynamic MRI is MVD but not VEGF expression; and 2) a functional, dynamic MRI approach may be more suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis.
Adult↗
Dipyridamole decreases renal phosphate leak and augments serum phosphorus in patients with low renal phosphate threshold.
It has been shown that an acute infusion of dipyridamole increased renal phosphate reabsorption in rats and humans. A prospective study was performed to determine whether chronic treatment by dipyridamole given orally could decrease renal phosphate leak and increase serum phosphorus in patients with idiopathic low renal phosphate threshold (TmPO4/GFR < 0.77 mM). Sixty-four patients with low TmPO4/GFR were included and treated with dipyridamole (75 mg, 4 times daily) for more than 12 mo. Serum phosphorus, TmPO4/GFR, parathyroid hormone, serum calcium, and 1,25-dihydroxyvitamin D were measured sequentially before treatment, and after 3, 6 to 9, and 12 mo of treatment. Under chronic treatment with dipyridamole, TmPO4/GFR and serum phosphorus significantly increased in 80% of patients within 3 mo, with maximal values reached within 9 mo. This improvement persisted after 12 mo of treatment. In 28 patients, 1,25-dihydroxyvitamin D concentrations were above the normal range (> 42 pg/ml) and normalized in parallel with the increase of serum phosphorus. The 24-h calcium excretion (which was initially increased in patients with high vitamin D concentrations) and urolithiasis decreased under treatment. Ionized serum calcium and parathyroid hormone remained unchanged. After 2 yr, treatment was discontinued in three patients; serum phosphorus and TmPO4/GFR decreased within 1 mo after discontinuation. Dipyridamole at a dose of 75 mg 4 times daily increases low TmPO4/GFR and improves hypophosphatemia in patients with renal phosphate losses and can be used to treat these patients.
Administration, Oral↗
Lovastatin modulates in vivo and in vitro the plasminogen activator/plasmin system of rat proximal tubular cells: role of geranylgeranylation and Rho proteins.
Interstitial fibrosis is one of the most deleterious events during the progression of renal deterioration after renal mass reduction. In vivo, hydroxymethylglutaryl CoA reductase inhibitors (HRI) were shown to reduce progression of glomerulosclerosis, but the mechanisms are still unclear. The present study investigates, in vivo, whether lovastatin, a potent HRI, was able to modulate the plasminogen-plasmin pathway, one of the most efficient systems involved in extracellular matrix remodeling, and characterizes in vitro the cellular mechanisms of these effects. Proximal tubules freshly isolated from rats treated for 2 d with lovastatin (4 mg/kg per d) showed increased tissue-type plasminogen activator (tPA) and urokinase (uPA) activities and antigens. Incubation with lovastatin (5 microM) of proximal tubules isolated from untreated rats induced an increase in tPA and uPA and a decrease in plasminogen activator inhibitor-1 (PAI-1) activities. In vitro, supernatants, cytosols, and membranes of renal proximal tubular cells in primary cultures had no detectable uPA activity, and lovastatin (0.1 to 10 microM) induced an increase in tPA and a decrease in PAI-1 activities and antigens. These effects were reversed by mevalonate and geranylgeranyl-pyrophosphate (GGPP) but not by farnesyl-pyrophosphate or LDL cholesterol. C3 exoenzyme, an inhibitor of the geranylgeranylated-activated Rho protein, reproduced the effect of lovastatin on tPA and PAI- activity and blocked its reversion by GGPP. The effect of lovastatin was associated with a disruption of cellular actin stress fibers, which was reversed by GGPP and reproduced by C3 exoenzyme. In conclusion, HRI can modify the fibrinolytic potential of proximal tubules, most likely via inhibition of geranylgeranylated Rho protein and disruption of the cytoskeleton. The resulting increase of proteolytic activity of tubular cells may serve to prevent extracellular matrix deposition and renal interstitial fibrosis.
Animals↗
Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement.
Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this project to: (a) examine the relationship between contrast-enhanced dynamic MRI-derived characteristics and histological microvessel density counts, a recognized surrogate of tumor angiogenesis, from primary or recurrent cancers of the uterine cervix; and (b) correlate these parameters with lymphatic involvement to characterize tumor aggressiveness in terms of lymphatic spread. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) were calculated from a contrast-enhanced dynamic MRI series in 55 patients (ages 25-72 years; mean, 50 years) with biopsy-proven primary (n = 42) or recurrent (n = 13) uterine cervical cancer. Both pharmacokinetic parameters were correlated to histologically determined microvessel density counts (factor VIII-related antigen) and other pathological tumor characteristics obtained from the operative specimens after radical surgery. In addition, the magnetic resonance and histological data were correlated to the presence or absence of lymphatic system involvement. Pharmacokinetic MRI-derived parameters (A and k21) increased with increasing histological microvessel density counts with r = 0.41 and 0.50, respectively. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k21 compared with histological microvessel density, resulting in a higher sensitivity, overall accuracy, and comparable specificity. Contrast-enhanced MRI parameters might prove to be applicable for estimation of tumor angiogenesis in uterine cervical cancer; thus, MRI may become an additional tool to characterize malignant progression in terms of lymphatic involvement in uterine cervical cancer.
Adenocarcinoma↗
[Disorders of acid-base equilibrium. Physiopathology, diagnosis, treatment].
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Acid-Base Equilibrium↗
[Contrast-enhanced MR "magnetization transfer technique". Improved tumor contrast, delineation and visibility of intracranial malignant gliomas and metastases in radiosurgical treatment planning].
AIMS: To improve tumor conspicuity and delineation on contrast-enhanced T1-weighted MR images with and without magnetization transfer (MT) contrast as a strategy to improve the macroscopic boost volume definition in the planning process of radiosurgery in patients with high grade gliomas or metastatic brain lesions. PATIENTS AND METHODS: Thirty-two patients (mean age 47 years) with histologically proven or suspected high grade glioma (n = 12) or metastatic brain lesions (n = 20) were prospectively examined by MR imaging. After the administration of gadolinium dimeglumine (0.1 mmol/kg body weight) the lesions were imaged with a T1-weighted MT-fast low angle shot (FLASH) pulse sequence and with a conventional T1-weighted SE sequence without MT saturation. RESULTS: The mean CNR of enhancing lesions on T1-weighted MT-FLASH was 15 +/- 5 compared to 11 +/- 4 on SE images, representing a significant (p < .01) improvement. The mean tumor diameter of malignant gliomas was significantly (p < .01) larger measured on T1-weighted MT-FLASH images compared to those obtained from T1-weighted SE images and were comparable for metastatic lesions. Lesion conspicuity and delineation were improved in 50% of patients with high grade gliomas and in 35% of patients with brain metastases. Lesion conspicuity was markedly improved in the posterior fossa. Additional contrast enhancing lesions were detected in 10% of patients with metastases on MT-FLASH images. CONCLUSIONS: It is concluded that contrast-enhanced MT-FLASH images may improve lesion detection and delineation in the planning process of radiosurgery in patients with intracranial high grade gliomas or metastases or even alter the treatment approach.
Adult↗
Functional neuroimaging in the assessment of CNS neoplasms.
Assessment of CNS neoplasms has focused traditionally on morphological analysis. Recent developments in MR sequence design now enable functional assessments. T1-weighted, as well as T2(*)-weighted, dynamic, gadolinium-enhanced, imaging can be used for assessment of vascularisation, permeability, and microcirculation of CNS neoplasms. Characterisation of cerebrovascular blood flow is possible using dynamic MR angiography, while neurofunctional imaging enables visualisation of local alterations in neuronal activity in stimulated cortical areas. Diffusion-weighted imaging can be used for improved delineation of neoplasms, while chemical shift imaging allows metabolic mapping of lesions and surrounding tissues. Implementation of these techniques can improve characterisation, information for therapy, planning and prognosis in clinical imaging of CNS neoplasms.
Brain↗