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Biomedical subjects

D Seitz

Publications and source records attributed to D Seitz.

At least 19 recordsLinked to original sources

MR imaging and (1)H spectroscopy of brain metabolites in hepatic encephalopathy: time-course of renormalization after liver transplantation.

PURPOSE: To evaluate changes in hydrogen 1 magnetic resonance (MR) spectroscopic findings in overt or subclinical hepatic encephalopathy (HE) after liver transplantation and to compare these changes with clinical outcomes and basal ganglia high signal intensity (BGH). MATERIALS AND METHODS: Twenty-two patients scheduled for liver transplantation and 17 healthy control subjects were examined with (1)H MR spectroscopy and standard nonenhanced MR imaging. Eight patients underwent complete MR imaging and (1)H spectroscopic examinations before liver transplantation and at 3-4-week, 12-28-week, and 10-12-month follow-up after liver transplantation. RESULTS: Before liver transplantation, typical (1)H spectroscopic changes-decreased myo-inositol (mI)/creatine (Cr) and choline (Cho)/Cr ratios and an elevated glutamine and glutamate (Glx)/Cr ratio-were found in 21 patients. Eighteen patients had BGH at T1-weighted imaging. Three to 7 months after liver transplantation, the mI/Cr and Glx/Cr ratios were within the normal range in five of eight and eight of eight patients, respectively, without any residual signs of subclinical or overt HE; however, at MR imaging, seven patients still had BGH. CONCLUSION: After successful liver transplantation, renormalization of HE-specific brain metabolite changes is detected at (1)H spectroscopy and precedes the disappearance of BGH. The neuropsychologic signs of subclinical or overt HE follow the changes seen at (1)H spectroscopy rather than those seen at MR imaging.

Adult↗

[MR proton spectroscopy to monitor the concentration changes in cerebral metabolites following a TIPS placement].

BACKGROUND AND AIMS: In chronic liver dysfunction with portal hypertension the risk of variceal bleeding can be lowered by intrahepatic portosystemic shunting (TIPS). Although less pronounced than in surgical shunting, hepatic encephalopathy (HE) is a well-known undesired side effect. In cerebral proton MR spectroscopy (MRS), HE can be detected by a specific pattern of brain metabolite changes (increase of glutamine/glutamate (Glx) and decrease of myo-inositol (ml) and choline (Cho)). The aim of this study was to examine whether, after TIPS implantation, there is a correlation of the reduction of the portosystemic pressure gradient (PSPG) and the cerebral metabolite changes and their correspondence to the clinical status. METHODS: We examined 10 cirrhotic patients (Child B, C) before and 3-20 days after TIPS implantation. Clinical examination was performed by a senior hepatologist. Localized MR spectra were acquired in parieto-occipital gray/white matter using a short echo time (TE = 5 ms) STEAM sequence. RESULTS: After TIPS we found an increase of Glx/(Cr + PCr) of 13%-40% and a decrease of ml(Cr + PCr) of 6%-46% with a positive (Glx: r = 0.71) respectively negative (ml: r = -0.59) correlation to the reduction of the PSPG. 7/10 patients with a reduction of the PSPG of more than 9 mmHg (9-17 mmHg) showed a clinical impairment of their HE. CONCLUSIONS: Short echo time cerebral MRS allows detection of finest HE specific metabolite changes and can therefore contribute positively to an individually optimized reduction of the PSPG during TIPS implantation.

Adult↗

Localized proton magnetic resonance spectroscopy of the cerebellum in detoxifying alcoholics.

An increased daily alcohol consumption results in neurological symptoms and morphological central nervous system changes, e.g. shrinkage of the frontal lobes and the cerebellar vermis. Brain shrinkage can be due to neuronal loss, gliosis, or alterations of (cell) membrane constitutes/myelin. Neuronal, glial, and metabolic changes can be measured in vivo with proton magnetic resonance spectroscopy. A total of 11 alcoholics and 10 age-matched volunteers were examined by magnetic resonance imaging and localized magnetic resonance spectroscopy at an echo time of 135 and 5 msec. Peak integral values were calculated for N-acetylaspartate (NAA), choline (Cho), myo-inositol (ml), glutamate/glutamine (Glx), and normalized to phosphocreatine/creatine (Cr). Patients had a significant shrinkage of the cerebellar vermis. NAA/Cr and Cho/Cr ratios were reduced in both sequences, but the NAA/Cr reduction was only significant in long echo time, although the Cho/Cr reduction was significant in short echo time. The ml/Cr and Glx/Cr ratios did not show any significant difference between volunteers and patients. The decrease of NAA/Cr in alcohol dependent patients is consistent with neuronal loss. The Cho/Cr decrease and an unchanged ml/Cr may reflect cell membrane modification or myelin alterations in alcohol-dependent patients. These changes lead to brain shrinkage, although hydration effects and gliosis are less likely.

Adult↗

Proton spectroscopy of human brain with very short echo time using high gradient amplitudes.

In localized proton magnetic resonance spectroscopy very short echo times (TE) are achieved to diminish signal loss due to T2 relaxation and to avoid phase distortions due to J-coupling. A sequence for single volume spectroscopy in human brain is described with a TE as low as 5 ms. Examinations were performed on a 1.5 T whole-body imager with actively shielded gradients. A self-designed stimulated echo acquisition mode (STEAM) sequence with very high amplitude spoiling gradients of 24 mT/m was used to take advantage of the whole potential of the gradient system. Optimization of TE was carried out by controlling spectral quality and localization in both phantom and volunteer measurements. Proton spectra of human brain were acquired in 21 healthy volunteers. Spectra of occipital white matter, parieto-occipital grey/white matter, and cerebellum revealed none or only small eddy current distortions at a TE of 5 ms. The volume of interest was 8-12 ml, repetition time was 1.5 s, and mixing time was 5 ms. Peak ratios of major metabolites referring to creatine were estimated and the relative standard deviations were calculated to determine interindividual reproducibility. The relative standard deviation of myo-inositol ranged from 6% to 11% within these brain regions whereas for glutamine and glutamate 7% to 16% were found.

Adult↗

[Acute tumor of the lower eyelid caused by spontaneous hemorrhage of an occult vascular anomaly].

PURPOSE: To present an unusual acute tumour of the lid. PATIENT: A 37-year-old female physician presented with a swelling and a slight hematoma of the right lower lid. Palpation revealed two firm painless nodules under an intact epidermis. The patient confirmed that the lesion had developed within only one day without a preceding trauma. Both eyes were morphologically and functionally normal. Motility was free, and there was no exophthalmus. After three weeks the palpable nodules had not changed substantially. Magnetic resonance imaging disclosed a space-occupying lesion resembling an old hemorrhage or an inflammation. Excision was performed which revealed a thrombus-like structure. Histology showed multiple endothelium-lined vessels that were densely filled with erythrocytes, hemorrhages within the connective tissue, and old hemosiderin deposits. However, no thrombus could be found. CONCLUSION: Although thrombosis was the preferred diagnosis on clinical findings, histology led to the diagnosis of a spontaneous hemorrhage most likely caused by an occult vascular malformation.

Adult↗

MR imaging and localized proton MR spectroscopy in late infantile neuronal ceroid lipofuscinosis.

PURPOSE: Late juvenile neuronal ceroid lipofuscinosis (NCL) is a lysosomal neurodegenerative disorder caused by the accumulation of lipopigment in neurons. Our purpose was to characterize the MR imaging and spectroscopic findings in three children with late infantile NCL. METHODS: Three children with late infantile NCL and three age-matched control subjects were examined by MR imaging and by localized MR spectroscopy using echo times of 135 and 5. Normalized peak integral values were calculated for N-acetylaspartate (NAA), choline, creatine, myo-inositol, and glutamate/glutamine. RESULTS: MR imaging revealed volume loss of the CNS, most prominently in the cerebellum. The T2-weighted images showed a hypointense thalamus and hyperintense periventricular white matter. Proton MR spectra revealed progressive changes, with a reduction of NAA and an increase of myo-inositol and glutamate/glutamine. In long-standing late infantile NCL, myo-inositol became the most prominent resonance. Lactate was not detectable. CONCLUSION: MR imaging in combination with proton MR spectroscopy can facilitate the diagnosis of late infantile NCL and help to differentiate NCL from other neurometabolic disorders, such as mitochondrial or peroxisomal encephalopathies.

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Bone mineral density in premenopausal women with oestrogen deficiency and symptomatic coronary heart disease.

Serum oestrogen deficiency is one of the main causes of osteoporosis in post-menopausal women. In premenopausal women, oestrogen deficiency is rare. In 13 premenopausal women with symptomatic coronary heart disease (CHD) and significantly reduced serum oestrogen levels, bone mineral density, determined by quantitative computed tomography (QCT), was not reduce. In these women, oestrogen deficiency was probably one risk factor for the development of CHD. The level of serum oestrogen that protects women from the development of CHD might be different from the level that protects them from early loss of bone mineral density. Seven of the 13 women had a history of tubal sterilisation. This might be a possible risk factor, causing ovarial dysfunction and oestrogen deficiency.

Adult↗

[Echo contrast agents for the color Doppler sonographic diagnosis of deep femoral venous thrombosis].

PURPOSE: Evaluation of an echo contrast medium (Echovist) for color-coded duplex sonography of deep venous thrombosis of the thigh. MATERIAL AND METHODS: In 19 patients with deep vein thrombosis of the thigh, diagnosed by contrast phlebography, 22 color-coded duplex sonography studies were performed for flow analysis at the top of the thrombus. During the studies 8.5 ml echo contrast medium were injected in an ipsilateral vein at the back of the foot. The flow signals of the non-enhanced color coded duplex sonography were compared with those of the echo enhanced study for differentiation between floating thrombi from those adherent to the vein wall. RESULTS: The echo-enhanced color-coded duplex sonography showed a significant increase in detection of perfusion at the top of the thrombus in comparison with non-enhanced color-coded duplex sonography (p < 0.01). 9 thrombi were regarded as wall adherent after the native study, 7 of these could be identified as floating thrombi by echo-enhanced color-coded duplex sonography. CONCLUSION: Echo-enhanced color-coded duplex sonography yields a significant increase of diagnostic information in certain findings of the non-enhanced color-coded duplex sonography differentiating between floating thrombi and wall adherent thrombi in the deep venous system of the thigh.

Adult↗

Magnetic resonance bone densitometry. Comparison of different methods based on susceptibility.

RATIONALE AND OBJECTIVES: Three different magnetic resonance techniques for the assessment of the density of trabecular bone are presented and compared. METHODS: All methods are based on the susceptibility difference between marrow and bony components. Localized spectroscopic (PRESS single voxel spectroscopy) and two different imaging approaches (FLASH gradient echo imaging and MAGSUS imaging) are demonstrated to be sensitive to the trabecular structures on application to the distal femur of a healthy volunteer. This region was chosen because a continuous rarefication of the trabecular density from the epiphysis to the metaphysis occurs physiologically. In addition, results from the heel-bones of five young healthy volunteers were compared with data from three patients with severe osteoporosis. RESULTS: All methods allowed differentiation between the two groups. Advantages and disadvantages of the methods concerning spatial resolution, preparation and measuring time, necessity of postprocessing, problems with shim adjustment, and occurrence of several chemical shift components are reported. The MAGSUS technique combines simple application and avoidance of postprocessing for at least qualitative assessment of bone density with sufficient spatial resolution. CONCLUSIONS: A reliable assessment of osteoporosis by magnetic resonance is possible in peripheral marrow regions of adults. Further studies are needed to establish standard measuring protocols.

Adult↗

Antitumor activity and clinical pharmacology of sulofenur in ovarian cancer.

BACKGROUND: Sulofenur is a diarylsulfonylurea with demonstrated antitumor activity in patients with advanced epithelial ovarian cancer refractory to standard chemotherapy. The dose-limiting toxic effects observed in phase I clinical trials have been anemia and methemoglobinemia, resulting in cyanosis. PURPOSE: The purposes of this study were to further define the response rate, toxic effects, and pharmacokinetics and pharmacodynamics of sulofenur in patients with advanced ovarian cancer. METHODS: We conducted a phase II trial of sulofenur at a dose of 800 mg/m2 per day in 35 patients with stage III or IV ovarian cancer refractory to standard chemotherapy. Pharmacokinetics and pharmacodynamics were analyzed by comparing sulofenur parent and metabolite plasma levels with methemoglobin levels. RESULTS: Partial responses lasting 6.5-18 weeks occurred in four (15%; 95% confidence interval = 4%-35%) of the 26 patients assessable for response. In addition, 42% (11) of the assessable patients had prolonged stable disease (median, 20 weeks). The first nine patients received sulofenur as a daily oral dose for 14 days, with a 21-day treatment cycle. However, they developed substantial anemia and methemoglobinemia. As a result, the next 26 patients received sulofenur daily for 5 days followed by 2 days of rest for 3 consecutive weeks, with a 28-day treatment cycle (5/2-day schedule). Preclinical models predicted that 2 days of rest would decrease toxicity while maintaining antitumor activity. Patients treated with the 5/2-day schedule had relatively less severe anemia and methemoglobinemia and needed fewer red blood cell transfusions (31% versus 78% of patients), but 31% still required dose reductions because of these toxic effects. The hydroxy and keto metabolites of sulofenur had prolonged plasma half-lives relative to the parent compound, and the difference was statistically significant. In addition, the correlations of metabolite concentrations with methemoglobin levels were higher than the correlation of sulofenur concentrations with methemoglobin levels, and those differences were statistically significant. CONCLUSION: We conclude that sulofenur has modest clinical activity in heavily pretreated patients with ovarian cancer. IMPLICATIONS: The toxic effects of anemia and methemoglobinemia may limit the ultimate clinical utility of diarylsulfonylureas until less toxic derivatives with alternate metabolic pathways can be identified.

Adult↗

Haemopoietic stem cells in mice chronically exposed to styrene vapour.

Female C57BL/6X DBA/2 hybrid mice were exposed to two concentrations of styrene in inhalation chambers for 6 h/day, 5 days per week. The concentrations were 220 ppm for a period of up to 8 weeks and 440 ppm for 2 days, followed by 330 ppm for up to 8 weeks due to early deaths after 440 ppm. Parallel groups were also treated with 5% ethanol in the drinking water during the days of styrene exposure. In the peripheral blood only a lymphocytopenia was found. The numbers of pluripotent haemopoietic stem cells, CFU-S, were unaffected, as were granuloid committed stem cells, CFU-C. Early and late erythroid stem cell numbers, BFU-E and CFU-E, showed high variability. At 220 ppm about half of the animals had CFU-E numbers below 80% of controls, at 440/330 ppm about two-thirds of the animals had BFU-E and CFU-E numbers below this level. An additional effect of ethanol was not found.

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