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Biomedical subjects

K P Braun

Publications and source records attributed to K P Braun.

At least 19 recordsLinked to original sources

[A benign abdominal schwannoma presenting as postrenal failure--a case report].

BACKGROUND: Benign schwannomas are uncommon soft-tissue tumors in childhood. The occurrence of an abdominal schwannoma effecting an acute postrenal failure has not been reported thus far. PATIENTS: It is to describe the case of a 14-year-old male teenager who was admitted to our department because of inappetence and oedema in his face and on both feet. Further diagnostic investigations demonstrated a 24x20x15 cm abdominal tumor, which lead to an acute postrenal failure. The resection of the intraperitoneal tumor was performed completely, the histopathological examination revealed a benign schwannoma. Subsequently, the renal function had rapidly to normalised and ten years after the operation he has had no tumor recurrence. CONCLUSIONS: Surgical excision in toto is the treatment of choice. The clinical presentation, differential diagnosis and operative strategy for benign and malignant abdominal schwannomas are discussed.

Abdominal Neoplasms↗

Body size and weight as predisposing factors in varicocele.

OBJECTIVE: The literature regarding the constitutional type of children and adolescents with varicocele is inconsistent. The aim of this investigation was to examine a possible influence of weight, height and body mass index (BMI) on the formation of varicoceles during childhood and adolescence. MATERIAL AND METHODS: In a retrospective data analysis, 193 Caucasian children and adolescents aged 9-19 years (mean age 14.7 years) with left-sided varicocele grade 2-3 were studied. The weight, height and BMI of the subjects were compared with the age-correlated normal values currently accepted in Germany. Additionally, the familial disposition for varicocele and the occurrence of relevant concurrent diseases were considered. RESULTS: In the group of patients examined, the mean percentiles of weight (57th) and height (58th) were significantly above and the mean BMI percentile (42th) was significantly below the age-correlated 50th percentile for the normal population (p=0.019, 0.005 and 0.002). In our case material, 12.2% of all brothers of the patients had varicoceles. CONCLUSIONS: The results of this investigation suggest a correlation between physical appearance and the formation of a varicocele during childhood or adolescence. We were able to demonstrate that patients with varicocele were heavier and taller than an age-correlated normal population, but had a distinctly lower BMI. Further studies are needed to verify whether this rather athletic habitus, together with the postulated difference in muscle:fat ratio, represents an important etiologic factor for varicocele formation.

Adult↗

Effect of mycophenolate mofetil on IMP dehydrogenase after the first dose and after long-term treatment in renal transplant recipients.

OBJECTIVE: Mycophenolate mofetil (MMF) is routinely used as an immunosuppressant in a fixed daily dose regimen although it shows marked fluctuations in pharmacokinetics, and despite the fact that in regard to the active metabolite, mycophenolic acid (MPA), there is a well-known association between the pharmacokinetic parameters and clinical outcome. METHOD: In order to determine the time course and the variability in cellular target of MPA after renal transplantation, we investigated the pharmacodynamic response in 8 patients receiving 1 g MMF for the first time prior to renal transplantation and in 8 stable renal transplant patients maintained on long-term MMF therapy (1 g b.i.d.) for more than 1 year. The pharmacodynamic response was measured using inosine 5'-monophosphate dehydrogenase (IMPDH) activity in peripheral mononuclear cells. MPA plasma concentrations were measured in parallel, IMPDH activity in 89 healthy blood donors was used as a control. RESULTS: We observed a high interindividual variability in IMPDH activity in the 89 untreated healthy volunteers (4.0 - 32.9 nmol/h/mg protein), in 8 patients on dialysis (5.3 - 18.9 nmol/h/mg protein) and in 8 renal transplant patients under long-term MMF treatment (2.3 - 14.4 nmol/h/mg protein). The mean AUC0-12h for mycophenolic acid was 2-fold higher in patients receiving long-term treatment with MMF (62.2 +/- 16.6 mg x h/ml) compared to dialysis patients receiving 1 g MMF for the first time (31.5 +/- 15.6 mg x h/ml). Despite this pharmacokinetic difference there were no statistically significant differences in the cellular pharmacodynamic response. Minimal IMPDH activity (1.62 +/- 1.23 vs. 1.77 +/- 1.49 nmol/h/mg protein) and maximal IMPDH inhibition (87.5 +/- 0.08 vs. 77.4 +/- 18.8%) during the dosing interval were similar. CONCLUSIONS: The considerable interindividual variability in the pharmacokinetics of MMF as well as in the drug target support the use of pharmacodynamic drug monitoring to optimize MMF dosing and to reduce the risk of graft rejection and side effects.

Area Under Curve↗

[An infant with pain and meningeal irritation due to Guillain-Barré syndrome].

In a five-month-old girl, who for a week had cried and displayed a relapse in the motor development, generalised hypotonia and meningism were found. Eventually, the results of the cerebrospinal fluid analysis and electromyography indicated Guillain-Barré syndrome. She was treated with immunoglobulins and made a quick recovery. Guillain-Barré syndrome is an acute or subacute inflammatory demyelinating polyradiculoneuropathy that can occur at any age. In children, the classic symptoms such as a flaccid paralysis and areflexia are not always predominant. Instead, pain is often the most prominent symptom, along with meningism. These symptoms are often insufficiently recognised in practice and as a result of this, delays in the diagnosis of this potentially life-threatening disease often occur.

Diagnosis, Differential↗

Single-shot diffusion trace (1)H NMR spectroscopy.

Ignoring diffusion anisotropy can severely hamper the quantitative determination of water and metabolite diffusion in complex tissues. The measurement of the trace of the diffusion tensor provides unambiguous and rotationally invariant ADC values, but usually requires three separate experiments. A single-shot technique developed earlier, originally designed for diffusion trace MR imaging (Mori and van Zijl, Magn Reson Med 1995;33:41-52), was improved and adapted for diffusion trace MR spectroscopy. A double spin-echo pulse sequence was incorporated with four pairs of bipolar gradients with specific predetermined relative signs in each of the three orthogonal directions. The combination of gradient directions leads to cancellation of all off-diagonal tensor elements while constructively adding the diagonal elements. Furthermore, the pulse scheme provides complete compensation for cross-terms between static magnetic field gradients and the applied diffusion gradients, while simultaneously avoiding cross-terms with localization gradients. The sequence was tested at 4.7 T in vivo on rat brain for MRI and on rat skeletal muscle and brain for MRS. It is shown that the average ADC as determined from the measurement of the ADCs in the three orthogonal directions is in close agreement with the ADC obtained along the trace of the diffusion tensor in a single acquisition, for both water and metabolite diffusion. The large differences in water and metabolite diffusion coefficients as measured in the individual orthogonal directions illustrate the need for diffusion trace measurements when accurate and rotationally invariant diffusion quantitation is required. The pulse scheme presented here may be applied for such purposes in MRS and MRI studies.

Algorithms↗

Diffusion NMR spectroscopy.

MR offers unique tools for measuring molecular diffusion. This review focuses on the use of diffusion-weighted MR spectroscopy (DW-MRS) to non-invasively quantitate the translational displacement of endogenous metabolites in intact mammalian tissues. Most of the metabolites that are observed by in vivo MRS are predominantly located in the intracellular compartment. DW-MRS is of fundamental interest because it enables one to probe the in situ status of the intracellular space from the diffusion characteristics of the metabolites, while at the same time providing information on the intrinsic diffusion properties of the metabolites themselves. Alternative techniques require the introduction of exogenous probe molecules, which involves invasive procedures, and are also unable to measure molecular diffusion in and throughout intact tissues. The length scale of the process(es) probed by MR is in the micrometer range which is of the same order as the dimensions of many intracellular entities. DW-MRS has been used to estimate the dimensions of the cellular elements that restrict intracellular metabolite diffusion in muscle and nerve tissue. In addition, it has been shown that DW-MRS can provide novel information on the cellular response to pathophysiological changes in relation to a range of disorders, including ischemia and excitotoxicity of the brain and cancer.

Animals↗

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study.

AIMS/HYPOTHESIS: It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood flow, could compromise cerebral energy metabolism. We therefore examined cerebral metabolism in streptozotocin-diabetic rats in vivo by means of localised 31P and 1H magnetic resonance spectroscopy. METHODS: Rats were examined 2 weeks and 4 and 8 months after diabetes induction. A non-diabetic group was examined at baseline and after 8 months. RESULTS: In 31P spectra the phosphocreatine:ATP, phosphocreatine:inorganic phosphate and ATP:inorganic phosphate ratios and intracellular pH in diabetic rats were similar to controls at all time points. In 1H spectra a lactate resonance was detected as frequently in controls as in diabetic rats. Compared with baseline and 8-month controls 1H spectra did, however, show a statistically significant decrease in N-acetylaspartate:total creatine (-14% and -23%) and N-acetylaspartate:choline (-21% and -17%) ratios after 2 weeks and 8 months of diabetes, respectively. CONCLUSION/INTERPRETATION: No statistically significant alterations in cerebral energy metabolism were observed after up to 8 months of streptozotocin-diabetes. These findings indicate that cerebral blood flow disturbances in diabetic rats do not compromise the energy status of the brain to a level detectable by magnetic resonance spectroscopy. Reductions in N-acetylaspartate levels in the brain of STZ-diabetic rats were shown by 1H spectroscopy, which could present a marker for early metabolic or functional abnormalities in cerebral neurones in diabetes.

Adenosine Triphosphate↗

Non-radioactive determination of inosine 5'-monophosphate dehydro-genase (IMPDH) in peripheral mononuclear cells.

BACKGROUND: The immunosuppressive activity of mycophenolate mofetil (MMF) is based on the reversible inhibition of inosine 5'-monophosphate dehydrogenase (IMPDH) by mycophenolic acid (MPA). It was the aim of this study to develop a nonradioactive method for specific measurement of IMPDH activity in isolated peripheral mononuclear cells (MNC). METHODS: The procedure is based on the incubation of lysed MNC with inosine 5'-monophosphate (IMP) followed by direct chromatographic determination of produced xanthosine 5'-monophosphate (XMP). IMPDH activity was measured in MNC of MMF-treated patients and nontreated volunteers. RESULTS: The within-run (n = 10) and between-run (n = 20) coefficients of variation (CV) for IMPDH activity were < 8% and < 10%, respectively. IMPDH activity in 60 healthy volunteers (19-63 yr) ranged from 4.72 to 32.92 nmol/h/mg protein (mean = 18.39 +/- 6.24). The IC(50) for in vitro inhibition of IMPDH activity was about 2 to 3 microg/L. Application of a single dose of 1 g MMF in dialysis patients resulted in a significant inhibition (by 47-95%; p < 0.05) of IMPDH activity in lysed MNC. CONCLUSIONS: The proposed assay specifically and reliably measures IMPDH activity in MNC. The procedure is applicable to evaluate pharmacodynamic activity in MMF-treated patients. The observed interindividual variability of IMPDH activity may reflect pharmacodynamic differences in MMF-treated patients.

Adult↗

[Epilepsy, disturbances of behavior and consciousness in presence of normal thyroxine levels: still, consider the thyroid gland].

Three patients, one man aged 51 years, and two women aged 49 and 52 years, had severe fluctuating and progressive neurological and psychiatric symptoms. All three had normal thyroxine levels but elevated thyroid stimulating hormone levels and positive thyroid antibodies. Based on clinical, laboratory, MRI and EEG findings they were eventually diagnosed with Hashimoto's encephalopathy, associated with Hashimoto thyroiditis. Treatment with prednisone in addition to thyroxine suppletion resulted in a remarkable remission of their neuropsychiatric symptoms. The disease is probably under-recognized.

Autoantibodies↗

In vivo glucose detection by homonuclear spectral editing.

A frequency-selective multiple-quantum-coherence spectral editing pulse sequence, Ssel-MQC, was implemented for the detection of the betaH1-glucose resonance at 4.63 ppm in rat brain in vivo. Unwanted signal suppression and glucose coherence transfer pathway selection were performed with magnetic field gradients. To optimize sensitivity, the sequence was executed with surface coil signal reception and adiabatic RF pulse transmission. The glucose editing capabilities of Ssel-MQC were first evaluated in vitro. Ssel-MQC achieved excellent water suppression (suppression factor >10(5)), at the expense of an approximately 60% loss of the glucose signal due to incomplete coherence transfer pathway selection. Next, the sequence was used for in vivo glucose detection in normal rat brain during D-glucose infusion and in the brain of diabetic rats prior to and following insulin infusion.

Animals↗

NMR spectroscopic evaluation of cerebral metabolism in hydrocephalus: a review.

Cerebral ischemia contributes to cerebral damage in hydrocephalus. Many studies have reported changes in cerebral blood flow and metabolism, supporting this hypothesis. Magnetic resonance spectroscopy (MRS) enables us to investigate cerebral metabolism in a non-invasive and longitudinal manner, thereby providing a promising way of evaluating pathophysiological changes in experimental and clinical hydrocephalus. In this review, the potential of 1H (proton) and 31P (phosphorus) MRS in the assessment of cerebral metabolism will be summarized, and a synopsis of in vitro and in vivo MRS studies in experimental and human hydrocephalus will be presented. Changes in high-energy phosphate metabolism, intracellular pH and lactate production in several MRS studies are presumed to reflect cerebral ischemia. In vivo information on neuronal damage, maturational delay and membrane phospholipid metabolism may also be derived from 1H and 31P MRS data. Technical, methodological and pathophysiological considerations, which are important for a correct interpretation and comparison of different MRS studies, will be discussed. Finally, we will draw some conclusions on the significance of these MRS findings and the applicability of MRS in the diagnosis and evaluation of clinical hydrocephalus.

Animals↗

[Clinical thinking and decision making in practice. A nurse with acute pain between shoulder blades].

A 50-year-old female nurse with an unremarkable medical history experienced acute midthoracic pain, irradiating to the chest and increasing during inspiration. Initial physical examination, laboratory tests, chest X-ray and electrocardiography all were normal. Pulmonary scintigraphy could not be performed in the early stage after admission. The clinical diagnosis of probable pulmonary embolism was made, and anticoagulant therapy was started. The following day, the patient gradually developed a spinal cord syndrome, eventually including paraplegia, bladder dysfunction and an incomplete sensory deficit with an upper level at the 5th thoracic dermatome, predominantly affecting temperature and pain sensation. Magnetic resonance imaging revealed a large anterior spinal epidural haematoma, extending from C7 down to T8. Urgent decompressive laminectomy and subsequent partial evacuation of the haematoma were performed, approximately 24 hours after the onset of neurological signs. No bleeding source was found during operation. The patient made a remarkable postoperative recovery.

Acute Disease↗

Cerebral metabolism in experimental hydrocephalus: an in vivo 1H and 31P magnetic resonance spectroscopy study.

OBJECT: Brain damage in patients with hydrocephalus is caused by mechanical forces and cerebral ischemia. The severity and localization of impaired cerebral blood flow and metabolism are still largely unknown. Magnetic resonance (MR) spectroscopy offers the opportunity to investigate cerebral energy metabolism and neuronal damage noninvasively and longitudinally. Previous 1H MR spectroscopy studies have shown an increased lactate resonance that is suggestive of anaerobic glycolysis. The aim of this study was to assess cerebral damage and energy metabolism in kaolin-induced hydrocephalus in adult rats by using in vivo 1H and 31P MR spectroscopy. The presence of lactate was correlated with high-energy phosphate metabolism and intracellular pH. The measurement of relative concentrations of N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr) served to assess neuronal damage. METHODS: Hydrocephalus was induced in adult rats by surgical injection of kaolin into the cisterna magna. Magnetic resonance studies, using a 4.7-tesla magnet, were performed longitudinally in hydrocephalic animals at 1 (10 rats), 8 (six rats), and 16 weeks (six rats) thereafter, as well as in eight control animals. To evaluate ventricular size and white matter edema T2-weighted MR imaging was performed. The 1H MR spectra were acquired from a 240-microl voxel, positioned centrally in the brain, followed by localized 31P MR spectroscopy on a two-dimensional column that contained the entire brain but virtually no extracranial muscles. The 1H and 31P MR spectroscopy peak ratios were calculated after fitting the spectra in the time domain, intracellular pH was estimated from the inorganic phosphate (Pi) chemical shift, and T2 relaxation times of 1H metabolites were determined from the signal decay at increasing echo times. CONCLUSIONS: In hydrocephalic rats, ventricular expansion stabilized after 8 weeks. White matter edema was most pronounced during acute hydrocephalus. Lactate peaks were increased at all time points, without a decrease in phosphocreatine (PCr)/Pi and PCr/adenosine triphosphate (ATP) peak ratios, or pH. Possibly lactate production is restricted to periventricular brain tissue, followed by its accumulation in cerebrospinal fluid, which is supported by the long lactate T2 relaxation time. Alternatively, lactate production may precede impairment of ATP homeostasis. The NAA/Cho and tCr/Cho ratios significantly decreased during the acute and chronic stages of hydrocephalus. These changes were not caused by alterations in metabolite T2 relaxation time. The decreases in the NAA/Cho and tCr/Cho ratios implicate neuronal loss/dysfunction or changes in membrane phospholipid metabolism, as in myelin damage or gliosis. It is suggested that 1H MR spectroscopy can be of additional value in the assessment of energy metabolism and cerebral damage in clinical hydrocephalus.

Animals↗

In vivo 1H MR spectroscopic imaging and diffusion weighted MRI in experimental hydrocephalus.

The severity and progression of ventricular enlargement, the occurrence of cerebral edema, and the localization of ischemic metabolic changes were investigated in a rat model of hydrocephalus, using in vivo 1H MR spectroscopic imaging (SI) and diffusion weighted MRI (DW MRI). Hydrocephalic rats were studied 1, 2, 4, and 8 weeks after injection of kaolin into the cisterna magna. Parametric images of the apparent diffusion coefficient (ADC) revealed a varying degree of ventriculomegaly in all rats, with different time courses of ventricular expansion. Extracellular white matter edema was observed during the early stages of hydrocephalus, most extensively in cases of progressive ventriculomegaly. In gray matter regions, ADC values were not changed, compared with controls. In case of fatal hydrocephalus, high lactate levels were observed throughout the whole brain. In all other rats, at all time points after kaolin injection, lactate was detected only in voxels containing cerebrospinal fluid. This suggests accumulation of lactate in the ventricles, and/or an ongoing periventricular production of lactate as a consequence of cerebral ischemia in experimental hydrocephalus.

Acute Disease↗

Cerebral ischemia and white matter edema in experimental hydrocephalus: a combined in vivo MRI and MRS study.

T2 and diffusion weighted MRI, as well as 31P and 1H MRS were performed in kaolin-induced hydrocephalic rats. Extracellular white matter edema was detected in the early stages of progressive hydrocephalus. Phosphocreatine (PCr)/inorganic phosphate (Pi) ratios in hydrocephalic animals were decreased compared to controls, and lactate was detected during the acute and chronic stages of hydrocephalus. These MR spectroscopic results are indicative of a compromised energy metabolism and suggest the occurrence of cerebral ischemia in experimental hydrocephalus.

Animals↗

A discriminant function for preeclampsia: case-control study of minor hemoglobins, red cell enzymes, and clinical laboratory values.

A case-control study was performed in eight pairs of women to determine whether preeclamptic women developed abnormalities in minor hemoglobins, glycolytic enzymes, or other blood components that might provide insight into the pathophysiology of preeclampsia, or that in combination might be used as a marker for the condition. These variables and standard clinical tests were analyzed as discriminators between preeclamptic and control women. The subjects were matched for age, ethnicity, parity, and gestational age. Blood samples were taken at the time of diagnosis of preeclampsia and at comparable gestational ages for matched normal controls. Variables differing significantly between groups included increases in uric acid (UA), low-density lipoproteins (LDL), phosphoglycerate kinase (PGK), and mean platelet volume (MPV), and decreases in glyceraldehyde phosphate dehydrogenase (G3PD) in preeclamptic women compared to normal controls. Discriminant analysis revealed the following function to separate the groups: 0.7764 (UA) + 0.8086 (PGK) -0.7032 (G3PD) + 0.1399 (LDL) -0.2386 (MPV). A discriminant score of > or = 275 indicated a > or = 90% probability of preeclampsia. The results are consistent with perturbations in red cell glycolysis in preeclampsia. Further prospective studies are warranted to test the efficacy of this discriminant function in predicting preeclampsia.

Adult↗

Stable acetaldehyde adducts: structural characterization of acetaldehyde adducts of human hemoglobin N-terminal beta-globin chain peptides.

Acetaldehyde is the first oxidation product of ethanol in vivo. Our earlier work showed that with sufficient acetaldehyde, five of the six possible sites of the peptide pentalysine were modified as a Schiff base (Braun KP, et al: J Biol Chem 270:11263-11266, 1995). However, we were unable to deduce unequivocally which site was unmodified. Lysine residues, as well as the amine terminal valine residues, in hemoglobin have been implicated as target structures for acetaldehyde adducts resulting from ethanol consumption. Hemoglobin adducts of acetaldehyde have been used clinically as a marker of ethanol consumption, but the chemical nature of these adducts remains undefined. As part of our continuing structural characterization of acetaldehyde-protein adduct formation, we studied the peptides Val-His-Leu-Thr-Pro and Val-His-Leu-Thr-Pro-Val-Glu-Lys, from the amine terminus of the beta-globin chain of hemoglobin, in vitro. Both peptides have at least one potential site for adduct formation. In the octapeptide, the N-terminal amine group of Val as well as the epsilon-amine group of the lysine sidechain can potentially be modified by acetaldehyde. We used mass spectrometry, carbon-13 nuclear magnetic resonance, and Raman spectroscopy and characterized stable Schiff base acetaldehyde adducts of these two peptides at both reactive sites. The identification of stable Schiff base adducts with the N-terminal peptides of the beta-chain of hemoglobin as well as with epsilon-amino groups of lysine provides another possible means of monitoring ethanol consumption. The functional implications of these stable Schiff bases remains undefined.

Acetaldehyde↗