Biomedical subjects
Publications and source records attributed to Michael Schulte.
Starting from pyrrole, the novel 3,4-didehydropyrohomoglutamate 8 or (ent)-8 can be efficiently synthesized in up to 91% ee, which can be utilized as a versatile building block toward functionalized pyrrolidin-2-ones. Moreover, (ent)-8 can be readily converted to (S)-Vigabatrin, being an irreversible inhibitor for GABA-T, which is used as adjunctive therapy in patients that suffer from epilepsy.
In this study, a case of fibromyxoma of the proximal femur in a 59-year old woman is reported. The classification of this rare bone tumour is still a matter of debate and some investigators have suggested that these lesions represent a degenerative form of fibrous dysplasia. Some authors make a further distinction between fibromyxoma and myxoma of bone. In a review of 23 cases of fibromyxoma and five cases of myxoma, no differences in clinical, radiographic and biologic behaviour between fibromyxoma and myxoma were found. Apart from the age at diagnosis, the most important difference between fibromyxoma and myxoma was the degree of myxoid matrix. Therefore, we suggest that extragnathic myxoma is a regressive variant of extragnathic fibromyxoma and should be termed as the same entity. In contrast to monostotic fibrous dysplasia fibromyxoma / myxoma often causes pain and presents as a Lodwick IC lesion with a soft tissue mass. Therefore, fibromyxoma / myxoma should be distinguished from fibrous dysplasia because of its different clinical and radiographic features.
Even if the first protein therapeutics are now for more than 20 years on the market the selection of suitable adsorbents for the preparative downstream processing (DSP) of these biomolecules as well as the method development towards process conditions are still based mainly on 'trial and error'. Therefore, theses processes are not perfectly efficient, but indeed very time consuming and laborious. In this study a novel systematic method is introduced to find a suitable adsorbent (not necessarily the best one) with appropriate separation parameters for a specific separation with reduced effort. Following this strategy, the adsorbents must first be packed into columns under preparative conditions and then characterized completely with regard to, e.g. pressure drop, k'-values, plate heights (HETP curves), selectivity and capacity by using test substances, which are similar in their characteristics (molecular mass, size, charge distribution, hydrophobicity) to the target proteins. With the database once determined, a preselection of most suitable adsorbents including separation parameters is made regarding chromatographic and also economical properties. After this, preparative experiments must be conducted with a reduced number of adsorbents to figure out the individual influence of side components. This approach is demonstrated for the separation of an exemplary industrial protein mixture using cation-exchange chromatography (CEX). Characterization of different weak CEX-adsorbents is illustrated. After comparing these phases with each other, a first preselection and a prediction of suitable adsorbents is made. In the following preparative separation conditions (load, velocity, gradient) are determined for the preparative separations using the database and results of some additional experiments. The final comparison of separation performance in preparative scale confirms this selection and so the applicability of the new method.
The role of preoperative embolization should be evaluated for the surgical treatment of spinal and pelvic metastases. Selective embolization was performed in 32 patients (19 men, 13 women; mean age 63.4 years) before surgery by anterior resection of spinal metastases (n = 21) or pelvic metastases (n = 11). Evaluation parameters consisted of the intraoperative blood loss, the need for blood replacement, and the operating time. There was a significant difference in blood loss and transfusion requirements in the spinal group (P = 0.02) as well as in the pelvic group (P = 0.05) compared to a nonembolized control group of spinal (n = 20) and pelvic (n = 10) metastases. The operating time in the embolized group was shorter, but the difference was not significant. Surgical revision was required in two cases in the embolized spinal group owing to necrosis of the psoas muscle. No neurological deficit was observed that could be attributed to the embolization procedure. Preoperative embolization is thus a suitable method for reducing intraoperative blood loss and transfusion requirements in hypervascularized spinal and pelvic metastases.
Individual treatment decisions can become considerably conflictual in view of the co-existence of medical professional guidelines, recommendations based on evidence-based medicine (EBM), and juridical and economical directions. Medical guidelines are not subject to an external review process; also, due to reduced practicability, the surgeons' compliance with guidelines remains relatively low. Surgical treatment strategies can rely on randomized clinical trials (RCTs) in approximately 20% of the surgical procedures and on non-randomized trials in approximately 70% of the cases. No evidence is given in approximately 10% of the cases. Specific problems of implementation of EBM in surgical disciplines are represented by the difficulty of standardized procedures, the heterogeneity of the population, the impossibility to conduct double-blinded RCTs, a low statistical power, and a publication bias. Since individual diseases cannot be reduced to surgical cases manageable only by the application of guidelines, adequate treatment of individual patients requires the critical application of both external evidence and surgeon expertise (internal evidence).
In 1942, Jaffe and Lichtenstein introduced the term aneurysmal bone cyst (ABC). Primary ABC is characterized by the presence of spongy or multi-cameral cystic tissue filled with blood. The process is benign, but it is locally destructive and has a high propensity for recurrence. In this paper, we present the third case of multiple metachronous primary ABCs as a rare variant of ABC. We describe the 10-year history of a 12-year-old boy with metachronous multiple primary ABCs at five different sites (right proximal humerus, right ulna, bilateral distal radius and right lateral clavicle). Furthermore, our patient suffered from vascular malformations, such as aortic isthmus stenosis, hypoplastic thoraco-abdominal aorta and bilateral renal artery stenosis. To date, in contrast to solitary ABC, the multiple lesions have been found more frequently in male individuals. Using interphase cytogenetics, we analyzed three of five of the patient's ABCs and one of these was also analyzed by GTG-banding. No chromosomal abnormalities were found. Significantly, we excluded the missense mutation of codon 201 in guanine nucleotide-binding protein 1 gene consistently found in McCune-Albright syndrome (MAS) and in non-MAS cases of polyostotic fibrous dysplasia of bone with or without secondary ABC.
The abnormalities covered by the generic term "oculo-auriculovertebral spectrum" (OAV) form an exceptional heterogeneous dysmorphic complex characterized by unilateral malformations of miscellaneous craniofacial structures. The aim of the present study was to analyze morphometrically the developmental deficits concerning the temporomandibular joints, the mandibular rami and the mastication muscles by comparing the affected with the non-affected side. The volume, maximum horizontal diameter, and trabecular bone density of the head of the mandible, as well as the ramus height were acquired from CT data of 16 patients suffering from this syndrome. The volume and maximal cross-sectional area of the masseter muscles and the pterygoid muscles were defined by quantifying CT data of nine patients. The skeletal parameters were evaluated with VoXim software. The comparison of the mandibular structures on the affected and on the non-affected side was based on the Wilcoxon signed rank test. The results recorded on the affected side showed that the TMJ volume was reduced by a mean factor of 7.98, and the spongiodensity of the head of the mandible by a mean factor of 1.33, while the mean reduction in ramus height was 14.89 mm. The muscle volumes on the affected side had also undergone a mean reduction of 9.10 cm(3). The CT-based data analysis proved to be an excellent tool for quantitative three-dimensional evaluation of both the skeletal and the muscular parameters.
Currently, there are over 40 oligonucleotide-based pharmaceutical products in various stages of clinical development for the treatment of an assortment of life-threatening diseases. As a result, the production of synthetic oligonucleotides has become increasingly important, with applications in antisense-, aptamer-, ribozyme-, immunostimulatory CpG molecule- and RNAi-related therapeutics. Due to the enormous commercial interest in these technologies, the manufacturing and purification processes for oligonucleotide production have been furtive and practiced in a confidential environment. As a result, limited information on large-scale processing is available in the scientific literature. The purpose of this article is to review the current state-of-the-art in oligonucleotide purification technologies, which have resulted in drug products meeting stringent therapeutic specifications. An indication of new and emerging purification technologies, including simulated moving bed- and membrane-based separation, is given.
The nucleoside 5-fluoro-2-deoxyuridine is a pyrimidine analogue accumulating in proliferative cells. We prospectively evaluated biodistribution of the PET tracer [(18)F]5-fluoro-2-deoxyuridine (FdUrd), its value for imaging malignant tumors, and its correlation to both [(18)F]2-fluoro-2-deoxyglucose (FDG)-PET findings and histological proliferation indices. In 11 previously untreated patients (5 lung carcinoma; 3 soft tissue sarcoma; 2 gastrointestinal carcinoma; 1 non-Hodgkin lymphoma [NHL]), mean doses of 290 MBq FdUrd and 390 MBq FDG were administered intravenously on subsequent days. Static PET scans were initiated 50-70 min after administration and the mean standardized uptake values (SUV) were calculated. Dynamic emission FdUrd scans were performed in 8/11 patients. Time-activity curves of blood and tumors as well as SUV of tumor lesions and organs were calculated. Proliferative activity was evaluated by Ki-67 immunohistostaining of biopsies. Tracer accumulated physiologically in liver, kidney, and bladder. SUVs were: kidney, 4.8 +/- 0.66; liver, 4.1 +/- 0.36; vertebrae, 0.70 +/- 0.17; spleen, 0.37 +/- 0.06; lungs, 0.19 +/- 0.05; femora/humeri, 0.14 +/- 0.03. Five patients exhibited significant intratumoral FdUrd-uptake (2 sarcomas; 1 NHL; 2 lung carcinomas) with mean SUVs ranging from 0.7 to 10.5. Metastases were not detected. Time-activity curves showed a rapid initial increase of intratumoral activity followed by activity retention. FDG-PET was positive in 10/11 patients. Correlation between the SUV of FdUrd-PET and FDG-PET or the tissue proliferation index, respectively, was not significant. FdUrd was a suitable tracer for imaging malignant tumors only in exceptional cases: Sarcoma, NHL, and some lung carcinomas were detected. FdUrd-PET was less effective than FDG-PET. In this group of patients, it was not useful in measuring tissue proliferation.
Auditory stimuli are encoded by frequency-tuned neurons in the auditory cortex. There are a number of tonotopic maps, indicating that there are multiple representations, as in a mosaic. However, the cortical organization is not fixed due to the brain's capacity to adapt to current requirements of the environment. Several experiments on cerebral cortical organization in musicians demonstrate an astonishing plasticity. We used the MEG technique in a number of studies to investigate the changes that occur in the human auditory cortex when a skill is acquired, such as when learning to play a musical instrument. We found enlarged cortical representation of tones of the musical scale as compared to pure tones in skilled musicians. Enlargement was correlated with the age at which musicians began to practice. We also investigated cortical representations for notes of different timbre (violin and trumpet) and found that they are enhanced in violinists and trumpeters, preferentially for the timbre of the instrument on which the musician was trained. In recent studies we extended these findings in three ways. First, we show that we can use MEG to measure the effects of relatively short-term laboratory training involving learning to perceive virtual instead of spectral pitch and that the switch to perceiving virtual pitch is manifested in the gamma band frequency. Second, we show that there is cross-modal plasticity in that when the lips of trumpet players are stimulated (trumpet players assess their auditory performance by monitoring the position and pressure of their lips touching the mouthpiece of their instrument) at the same time as a trumpet tone, activation in the somatosensory cortex is increased more than it is during the sum of the separate lip and trumpet tone stimulation. Third, we show that musicians' automatic encoding and discrimination of pitch contour and interval information in melodies are specifically enhanced compared to those in nonmusicians in that musicians show larger functional mismatch negativity (MMNm) responses to occasional changes in melodic contour or interval, but that the two groups show similar MMNm responses to changes in the frequency of a pure tone.
OBJECTIVE: Microsurgical resection or ventriculoperitoneal shunt placement was for a long time the only means of treatment for patients with colloid cysts. In the past few years, however, endoscopic procedures have gained increasing significance and have been used more widely. Long-term results are now available for the first time, which enabled us to evaluate this method and assess its future relevance. METHODS: Twenty patients with symptomatic colloid cysts of the third ventricle have been treated endoscopically in our department during the past 10 years. Retrospective analysis and follow-up of the patients' clinical and radiological outcomes were performed. RESULTS: In the early postoperative period, 18 patients had excellent outcomes, with clinical signs improving immediately. One patient experienced intraoperative hemorrhage followed by temporary postoperative psychosis and IIIrd cranial nerve palsy. Another patient remained shunt-dependent because of aseptic meningitis after the endoscopic procedure. In the long-term follow-up, one patient had to be reoperated to treat cyst recurrence. The operative time was strongly dependent on the cyst material as well as on the surgeon's experience with endoscopic techniques; it varied between 60 and 300 minutes (mean operative time, 200 min). The average hospitalization time was 9 days. Long-term follow-up ranging from 1 to 10 years showed a clear benefit in each patient. In three individuals with pre- and postoperative short-term memory deficits and in one patient who complained of headaches, symptoms resolved gradually during the first few months after surgery. The patient with intraoperative hemorrhage complained of slight permanent short-time memory deficit. The analysis of postoperative computed tomographic and magnetic resonance imaging scans revealed a remaining cyst wall in the majority of patients and an inconsistent decrease in ventricular size. Postoperative cine magnetic resonance imaging studies showed normalization of cerebrospinal fluid flow in 17 patients. CONCLUSION: Continued improvement of endoscopic techniques and instruments, together with good long-term results in endoscopically treated patients, have established this method as an alternative to microsurgical techniques and might even set a new standard for treatment.
A separation strategy for the preparative enantioseparation of intermediates of the synthesis route towards the new antithrombotic drug Gantofiban is outlined. The selectivities of six different intermediates on a series of chiral stationary phases of the poly-[N-(meth-)acryloyl amino acid derivative]-type are determined. The separations are optimized with respect to high enantioselectivities and good solubilities in the mobile phase. For three optimized combinations of chiral stationary and mobile phases the separation parameters for a simulated moving bed-systems are determined.
We designed a melody perception experiment involving eight harmonic complex tones of missing fundamental frequencies (hidden auditory object) to study the short-term neuronal plasticity of the auditory cortex. In this experiment, the fundamental frequencies of the complex tones followed the beginning of the virtual melody of the tune "Frère Jacques". The harmonics of the complex tones were chosen so that the spectral melody had an inverse contour when compared with the virtual one. Evoked magnetic fields were recorded contralaterally to the ear of stimulation from both hemispheres. After a base line measurement, the subjects were exposed repeatedly to the experimental stimuli for 1 hour a day. All subjects reported a sudden change in the perceived melody, indicating possible reorganization of the cortical processes involved in the virtual pitch formation. After this switch in perception, a second measurement was performed. Cortical sources of the evoked gamma-band activity were significantly stronger and located more medially after a switch in perception. Independent Component Analysis revealed enhanced synchronization in the gamma-band frequency range. Comparing the gamma-band activation of both hemispheres, no laterality effects were observed. The results indicate that the primary auditory cortices are involved in the process of virtual pitch perception and that their function is modifiable by laboratory manipulation.
We present 2 cases of hibernoma, a rare lipomatous tumor arising from brown fat tissue. In each case, a hyperechoic mass in comparison to surrounding musculature combined with elevated vascularization was highly suggestive of a liposarcoma. As a rule, malignancy cannot be excluded safely by imaging modalities, and a preoperative biopsy should be performed. Although rare, hibernomas should be considered in the differential diagnosis of lipomatous soft-tissue tumors.