Biomedical subjects

M Wilke

Publications and source records attributed to M Wilke.

At least 19 recordsLinked to original sources

PubMed2006

Diffusion-weighted magnetic resonance imaging of treatment-associated changes in recurrent and residual medulloblastoma: preliminary observations in three children.

PURPOSE: To emphasize a possible role of magnetic resonance (MR) diffusion-weighted imaging (DWI) for lesion conspicuity and detection of treatment effects in children with medulloblastoma. MATERIAL AND METHODS: Three children with medulloblastoma (two residual and one recurrent) were examined repetitively by MR diffusion-weighted imaging. Regional assessment of the apparent diffusion coefficient (ADC) was done for tumorous lesions and periventricular white matter appearing normal on standard MR images. RESULTS: All lesions were clearly visible on DWI. In the case of recurrent tumor, on one scan, DWI showed lesions that were not seen on contrast-enhanced MRI. Increase (41%) of ADC was seen in one lesion, which subsequently responded completely to treatment over 27 months' follow-up. Intermediate increases (23-26%) of ADC were found with partial therapy response in three lesions. In contrast, a decrease (-11%) of ADC in two lesions was seen with tumor progression. CONCLUSION: These observations may suggest a role for DWI in early detection of metastatic disease and treatment monitoring of medulloblastoma, warranting a formal study.

Adolescent↗

PubMed2006

The diallelic locus encoding the minor histocompatibility antigen HA-1 is evolutionarily conserved.

The polymorphic minor histocompatibility antigen HA-1 induces powerful T-cell alloreactivities with important consequences for graft-vs-tumor activity and development of graft-vs-host disease in patients after human leukocyte antigen-matched stem-cell transplantation (SCT). In view of possible translational animal studies, we analyzed the evolutionary conservation of the diallelic HA-1 locus in four mammalian species. Our results show that rodents do not encode the HA-1(H) allele, neither show polymorphism in this position on the HA-1 gene. Contrariwise, the HA-1(H) allele is present in non-human primate species and dogs. Interestingly, both the HA-1(H) T-cell epitope and its non-immunogenic counterpart HA-1(R) are present in the latter species. Thus, the HA-1 allelic polymorphism is conserved in evolution in primates and dogs.

Alleles↗

PubMed2005

1H-MRS alterations in the cerebellum of patients with familial hemiplegic migraine type 1.

BACKGROUND: About 20% of patients with familial hemiplegic migraine (FHM) develop progressive cerebellar signs. Genetic studies have established an association with mutations in the CACNA1A gene. However, the mechanisms underlying cerebellar involvement are largely unknown. OBJECTIVE: To use proton MR spectroscopy (1H-MRS) to investigate metabolic alterations in the cerebellum as well as cortical regions known to be involved in the propagation of migraine aura. METHODS: Fifteen CACNA1A mutation carriers from three FHM families and 17 healthy control subjects were studied. Eleven patients had clinical signs of cerebellar involvement. LCModel fits were used to estimate absolute concentrations of N-acetyl aspartate (NAA), myo-inositol (mI), glutamate (Glu), choline-containing compounds, total creatine, and lactate in the superior cerebellar vermis (SCV), parietal cortex, and occipital cortex. To control for atrophy effects, automated image segmentation was performed using SPM99. The brain parenchyma fraction (BPF) was determined for all three regions. RESULTS: Compared with controls, the brain parenchyma fraction (BPF), NAA, and Glu were significantly reduced and mI was significantly elevated in the SCV of patients with FHM. In contrast, no metabolite alterations were found in supratentorial regions. BPF and NAA in the SCV significantly correlated with cerebellar scores, in particular, gait ataxia. CONCLUSIONS: The findings suggest that there is a regionally distinct neuronal impairment in the superior cerebellar vermis that exceeds macroscopic tissue loss. Correlations with clinical scores emphasize the functional relevance of localized atrophy (brain parenchyma fraction) and N-acetyl aspartate levels. These measures may be useful to monitor disease progression. The observed reduction in glutamate may in part reflect impaired glutamatergic neurotransmission.

Adolescent↗

PubMed2005

[Maillard reaction products in food as pro-inflammatory and pro-arteriosclerotic factors of degenerative diseases].

Heating of food induces the formation of Maillard reaction products (MRPs) caused by the reaction of reducing sugars with proteins or amino acids. Analogous reactions occur in the human body, eventually forming "Advanced Glycation Endproducts" (AGEs). AGEs accumulate in aging tissues accelerating degenerative-inflammatory and proliferative processes. MRPs present in food can also directly cause inflammatory processes in the intestines and, once absorbed, would support and reinforce any inflammatory and degenerative process occurring in the body. The contribution of AGEs (and additional MRPs) in the development of diabetic complications as well as nephropathy, neuropathy, micro- and macroangiopathies is now well established. Which of the MRPs or AGEs in particular induce these cellular processes is currently unknown. Thus the exact knowledge of the chemical structures of the MRPs could help to minimize the formation of "harmful MRPs" that occur due to heating in food processing. Because MRPs play a decisive role in the successful marketing of edibles due to their characteristics as flavor components, it is important to increase the amount of innocuous and palatable MRPs, and minimize signal active pro-inflammatory MRPs by the use of defined preparation methods. It is practicable to use low-priced immunological methods for the quantitative determination of specific MRPs or AGEs. In the medical area, the knowledge of the signal active MRP/AGE structures provides the opportunity to measure their concentrations in body fluids and tissues and thus determine their influence on inflammatory and age-related degenerative processes (e. g., late diabetic complications, arteriosclerosis, degeneration of neurons). From a clinical perspective, the application of RAGE antagonists after an appropriate chemical diagnosis could be effective in supporting the treatment of affected patient groups, especially older diabetic and dialysis patients.

Aged↗

PubMed2005

[Ocular changes in tropical malaria with cerebral involvement--results from the Blantyre Malaria Project].

INTRODUCTION: Malaria is a tropical disease causing an estimated 300 million infections and one million deaths per year. In sub-Saharan Africa, most infections are due to Plasmodium falciparum. The hallmark of the clinical syndrome of cerebral malaria is coma, and the associated mortality rate, even in appropriately treated patients, is 15 - 50 %. Funduscopy plays a major role for the ophthalmologist in the differential diagnosis because of the characteristic changes. METHODS: To date more than 1000 children who satisfied the standard clinical case definition of cerebral malaria were admitted to the Blantyre Malaria Project (Malawi, Africa) for inpatient treatment and examined using indirect ophthalmoscopy through fully dilated pupils. The gender distribution was homogeneous and the children were between 2 and 14 years old. The optic nerve head, central and peripheral retina and central and peripheral vessels were described and photographed using a hand-held fundus camera (KOWA). RESULTS: The spectrum and severity of findings of the ocular fundus in children with CM include the following distinct entities: haemorrhages (with and without a white centre), cotton wool spots, papilloedema, retinal whitening and retinal vessel abnormalities that may appear to be orange or white. Most of the retinal haemorrhages (in 40 %) have white centres and resemble Roth spots. Cotton wool spots were seen in only 5 %. Papilloedema was also not commonly seen (8 %) but is a poor prognostic sign. Retinal whitening (in 50 %) is seen more commonly at the posterior pole than in the periphery. 20 % of patients show retinal vessel abnormalities that may be orange or white in colour. CONCLUSION: Ocular fundus changes in CM can be detected by the ophthalmologist using simple means and are decisive for the prognosis and timely therapy for this potentially lethal disease.

Adolescent↗

PubMed2005

[Histomorphometric evaluation of bone ingrowth of porous titanium by a computer-assisted analyzing system].

The objective of this study was to evaluate the bone ingrowth of a new vacuum plasma sprayed titanium surface (vps-ti) in comparison to cs-titanium implants in a göttinger minipig model. Fifteen göttinger minipigs each received the two implants, vacuum plasma sprayed titanium with a porosity of 50% and a pore size of 200 microm (vps-ti) and an implant with a similar porosity but a different pore size 500 microm (cs-ti), at the proximal femur metaphysis by press-fit technique. The pigs were euthanized at three different postsurgical periods: 4, 8 and 12 weeks. Each femur was harvested and qualitative (macroscopic and microscopic) and quantitative (histomorphometric) histological analysis was done on histological slides. The results indicated that there was a difference in bone ingrowth between the two implants, whereas the bone ingrowth of vps-ti was superior to cs-ti after 4 and 8 weeks healing time. 12 weeks post implantationem no statistiscal difference was evident. The pore size of 200 microm seemed superior to a pore size of 500 microm. Whether or not these effects lead to a better mechanical stability remains unanswered.

Animals↗

PubMed2004

Escherichia coli-nitroreductase suicide gene control of human telomerase reverse transcriptase-transduced minor histocompatibility antigen-specific cytotoxic T cells.

Adoptive immunotherapy with ex vivo generated cytotoxic T lymphocytes (CTLs) is applied for the treatment of leukemia relapses or viral infections after allogeneic stem cell transplantation. A common problem of adoptive immunotherapy strategies is the ex vivo expansion of the generated T cells to sufficient numbers. CTLs can be efficiently expanded by ectopic expression of the human telomerase gene (hTert). However, hTert transduction may also increase the chance for malignant transformation. Therefore, we explored the feasibility of suicide gene control of ex vivo generated CTLs expanded through the ectopic expression of hTert. To this end, we compared the efficacy of the new Escherichia coli-nitroreductase (E. coli-Ntr) suicide gene with the well-known herpes simplex virus-thymidine kinase (HSV-Tk). Introduction of hTert provided the transduced CTLs with a distinct growth advantage over the nontransduced CTLs. The hTert-E. coli-Ntr double-transduced CTLs retained their antigen-specific functions. Treatment of hTert-E. coli-Ntr double-transduced CTLs with metronidazole significantly inhibited the proliferation to a similar extent to the treatment of hTert-HSV-Tk double-transduced CTLs with ganciclovir. This is the first application of the E. coli-nitroreductase gene for the elimination of human T cells with metronidazole.

DNA-Binding Proteins↗

PubMed2003

Normative pediatric brain data for spatial normalization and segmentation differs from standard adult data.

Spatial normalization and morphological studies of pediatric brain imaging data based on adult reference data may not be appropriate due to the developmental differences between the two populations. In this study, we set out to create pediatric templates and a priori brain tissue data from a large collection of normal, healthy children to compare it to standard adult data available within a widely used imaging software solution (SPM99, WDOCN, London, UK). Employing four different processing strategies, we found considerable differences between our pediatric data and the adult data. We conclude that caution should be used when analyzing pediatric brain data using adult a priori information. To assess the effects of using pediatric a priori brain information, the data obtained in this study is available to the scientific community from our website (www.irc.cchmc.org).

Adolescent↗

PubMed2003

Automated detection of gray matter malformations using optimized voxel-based morphometry: a systematic approach.

Malformations of cortical development (MCD) are a recognized cause of epilepsy. Their special significance lies in the fact that, once detected and delineated, they are amenable to surgical removal. However, diagnosis from high-resolution MRI is still difficult, time-consuming, and highly dependent on individual expertise. We have recently proposed a simple procedure to detect cortical dysplasias, using automated procedures available within SPM99 (Wellcome Department, University College London, UK). Here, we aimed to systematically determine the best combination of processing parameters, using an optimized voxel-based morphometry approach. We included 20 patients with a known MCD and compared them to a normal database of 53 healthy, age- and gender-matched controls. The approaches taken during spatial normalization and a number of other parameters were systematically altered in order to find the best combination of parameters. Overall, 99 different approaches were evaluated in different ways. As far as possible, automatic processing and evaluation steps were used. With the number of candidate regions for MCD limited to five per patient, the best approaches resulted in the correct identification of up to 16 of 20 malformations. However, a number of approaches failed to perform well. The reasons for these failures and the implications this has for other studies are discussed. We conclude that voxel-based morphometry is able to detect cortical malformations with a high degree of accuracy. However, specific problems seem to arise when using an optimized protocol for voxel-based morphometry, indicating that this protocol may not be optimal for all voxel-based studies on brain morphology. Our approach, involving systematic alterations of parameters and evaluation, may be useful for other studies.

Adolescent↗

PubMed2003

A voxel-based morphometric MRI study in female patients with borderline personality disorder.

Subtle prefrontal and limbic structural abnormalities have been reported in borderline personality disorder (BPD). In order to further validate the previously reported findings and to more precisely describe the nature of the structural change we performed a voxel-based morphometric (VBM) study in patients with BPD. Twenty female patients with BPD and 21 female healthy controls were investigated. High-resolution 3-D datasets were acquired and analyzed following an optimized protocol of VBM in the framework of statistical parametric mapping (SPM99). Gray matter volume loss was found in the left amygdala. No other differences in gray or white matter volume or density were found anywhere else in the brain. Our findings support the hypothesis that temporolimbic abnormalities play a role in the pathophysiology of BPD. Prefrontal structural alterations in BPD were not observed in this study.

Adult↗

PubMed2003

[DRG-based cost analysis of inpatient conservative treatment of stage III/IV peripheral arterial occlusive disease].

UNLABELLED: DRG-based cost analysis of inpatient conservative treatment of PAD stage III/IV BACKGROUND: In a prospective study carried out by the German Society of Angiology and the DRG Competence Center, Munich, the question was investigated whether the costs of conservative treatment of patients with PAOD stage III/IV (DRG F65) are adequately represented within the current G-DRG system. METHODS UND PATIENTS: Between September 1 and December 16, 2002, a total of 704 patients with DRG F65 (peripheral vascular diseases) were evaluated at 8 angiologic centers in Germany. Apart from the length of hospital stay, the total costs (cost equivalents) were calculated using a method developed by the DRG Research Group at the University of Münster. Moreover, the study population was compared with a German calculation sample for the DRGs F65A/B, as published by InEK. RESULTS: As it turned out, conservatively treated patients with PAOD stage III or IV (DRGs F65A/B) cause significantly (p < 0.001) higher costs and have significantly (p < 0.001) greater lengths of hospital stay than patients who were also assigned to DRG F65 because of other vascular diseases. At the same time it became clear that angiologic centers treat twice as many patients with critical limb ischemia in comparison with the German average. The reimbursement hitherto estimated by InEK covers not even half the cost actually produced by conservative treatment of PAD stage III/IV. CONCLUSION: To ensure a performance-related reimbursement, a new basis DRG for patients with PAD stage III/IV has to be created, as has ben proposed by the German Society of Angiology. Otherwise, adequate conservative therapy in accordance with existing guidelines, of patients who cannot be treated surgically or interventionally will not be possible any more in the future.

Arterial Occlusive Diseases↗

PubMed2003

Functional magnetic resonance imaging in pediatrics.

Functional magnetic resonance imaging (fMRI) allows non-invasive assessment of human brain function in vivo by detecting blood flow differences. In this review, we want to illustrate the background and different aspects of performing functional magnetic resonance imaging (fMRI) in the pediatric age group. An overview over current and future applications of fMRI will be given, and typical problems, pitfalls, and benefits of doing fMRI in the pediatric age group are discussed. We conclude that fMRI can successfully be applied in children and holds great promise for both research and clinical purposes.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

The prevention of intrapartum HIV/AIDS transmission from mother to child.

The transmission of HIV/AIDS from mother to child is the main cause of HIV/AIDS in children and child mortality. Two-thirds of children with HIV/AIDS are infected in the intrapartum period (Farley, 2000:1-2). Midwives, through effective practices, can lower the transmission of HIV/AIDS from mother to child in the intrapartum period. The aim of the study was to determine which preventive practices registered midwives in provincial labour wards in Bloemfontein, implement to lower the risk of mother to child transmission of HIV/AIDS and in doing so to lower child mortality. A descriptive research design was used. Fifty-one midwives completed questionnaires to determine what preventive practices are used. The study showed that most of the midwives did not implement the interventions that could lower the chances of HIV/Aids transmission from mother to child during the intrapartum period. Midwives therefore may not have a positive impact on child mortality. The researchers concluded that midwives do not implement the interventions mentioned in the study because of a lack of knowledge and skills. Of the midwives who completed questionnaires, 67% completed their training between 1990 and 2000. This lack of knowledge may be due to a lack in the curriculum of training institutions and of an up-to-date policy concerning the transmission of HIV/Aids in provincial institutions in Bloemfontein. It is recommended that all affordable interventions should be incorporated in the policy.

Attitude of Health Personnel↗

PubMed2002

Allele specific PCR for the minor Histocompatibility antigen HA-2.

The hematopoietic system restricted minor Histocompatibility antigen (mHag), HA-2, is encoded by the novel human class I Myosin gene, MYO1G, located on the short arm of chromosome 7. The HA-2 encoding region is di-allelic and comprises the HLA-A2 restricted T cell epitope YIGEVLVSV (HA-2V) and its allelic counterpart YIGEVLVSM (HA-2M). We designed a sequence specific PCR (SSP) for both HA-2 alleles. The HA-2 genomic typing results were compared with the HA-2 CTL phenotyping in three families and revealed exact correlation. The mHag HA-2 SSP can be incorporated in DNA based typing protocols.

Alleles↗

PubMed2001

Reduced NAA in the thalamus and altered membrane and glial metabolism in schizophrenic patients detected by 1H-MRS and tissue segmentation.

Functional and structural abnormalities in the thalamus as well as a generalized phospholipid membrane disorder have been implicated in the pathogenesis of schizophrenic psychosis. To determine whether thalamic neuronal abnormalities and altered membrane-associated metabolites can be detected in schizophrenic patients, we used in vivo proton magnetic resonance spectroscopy (1H-MRS) in 32 acutely-ill, medicated schizophrenic patients and 17 age-matched controls. Thalamic and white matter metabolite concentrations (myo-inositol (mI), choline-containing compounds (Cho), total creatine (Cr) and N-acetylaspartate (NAA)) were estimated and corrected for atrophy (CSF) and gray and white matter contributions (GM, WM) by use of image-based voxel segmentation. Thalamic NAA was significantly reduced in schizophrenic patients, whereas Cho and mI were significantly increased in the parietal white matter. White matter Cr was significantly elevated in patients and correlated positively with the brief psychiatric rating scores (BPRS). Regional metabolite levels were inversely associated with GM and WM content reaching significance for mI and Cr in the thalamus and Cho and NAA in the white matter. Reduced NAA in the left thalamus of schizophrenic patients confirms and extends previous spectroscopic data and agrees well with histologic and imaging findings of reduced neuronal density and volume. Elevated Cho in line with 31P-MRS studies suggests increased myelin degradation thus further supporting a generalized membrane disorder in schizophrenic patients. In addition, we demonstrate the need to correct metabolite concentrations for regional tissue composition in studies employing patients with altered brain morphology.

Adult↗

PubMed2001

Fractures of the palmar aspect of the carpal bones in horses: 10 cases (1984-2000).

OBJECTIVE: To determine clinical and radiographic findings, treatment, and outcome of horses with fractures of the palmar aspect of the radial carpal bone, with or without concurrent fractures of the palmar surfaces of the other carpal bones. DESIGN: Retrospective study. ANIMALS: 10 horses. PROCEDURE: Medical records were reviewed to obtain information on history, signalment, clinical and radiographic findings, treatment, and outcome. Follow-up information was gathered from owners and referring veterinarians. RESULTS: 7 horses became lame after recovery from general anesthesia for treatment of an unrelated problem. The remaining 3 horses developed a fore-limb lameness after falling (1 horse) or being turned out in a pasture (2 horses). Fractures involved the palmar surface of the radial carpal bone in all 10 horses; in addition, the ulnar carpal bone was affected in 2 horses, the intermediate carpal bone in 2 horses, and the distal aspect of the radius in 4 horses. None of the 4 horses treated nonsurgically returned to work, and 3 were euthanatized because of recalcitrant lameness. In the other 6 horses, fragments were removed surgically. Two were euthanatized because of continued lameness, 1 was euthanatized for other reasons, 2 were sound enough for light work, and 1 returned to athletic work. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that fractures of the palmar aspect of the carpal bones are uncommon in horses. The prognosis appears to be poor for affected horses but may be better for horses that undergo arthroscopic removal of intra-articular fragments.

Animals↗

PubMed2001

The HA-2 minor histocompatibility antigen is derived from a diallelic gene encoding a novel human class I myosin protein.

Human minor histocompatibility Ags (mHag) present significant barriers to successful bone marrow transplantation. However, the structure of human mHag and the basis for antigenic disparities are still largely unknown. Here we report the identification of the gene encoding the human mHag HA-2 as a previously unknown member of the class I myosin family, which we have designated MYO1G. The gene is located on the short arm of chromosome 7. Expression of this gene is limited to cells of hemopoietic origin, in keeping with the previously defined tissue expression of the HA-2 Ag. RT-PCR amplification of MYO1G from different individuals led to the identification of two genetic variants, designated MYO1G(V) and MYO1G(M). The former encodes the peptide sequence previously shown to be the HA-2 epitope (YIGEVLVSV), whereas the latter shows a single amino acid change in this peptide (YIGEVLVSM). This change has only a modest effect on peptide binding to the class I MHC-restricted element HLA-A*0201, and a minimal impact on recognition by T cells when added exogenously to target cells. Nonetheless, as detected using either T cells or mass spectrometry, this amino acid change results in a failure of the latter peptide to be presented at the surface of cells that express MYO1G(M) endogenously. These studies have thus identified a new mHag-encoding gene, and thereby provide additional information about both the genetic origins of human mHag as well as the underlying basis of an Ag-positive vs Ag-negative state.

Alleles↗

PubMed2001

Determination of the iron oxidation state in earth materials using XANES pre-edge information.

Fe K-edge XANES spectra have been measured in more than 35 Fe(II) and Fe(III)-bearing minerals. The separation between the average pre-edge centroid positions for Fe(II) and Fe(III) is 1.4 +/- 0.1 eV. Examination of calculated pre-edge features of mechanical mixtures of phases containing different proportions of Fe(II) and Fe(III) reveals that different trends of pre-edge position vs. pre-edge intensity can be observed, depending on the coordination environment. Both pre-edge parameters have been used to estimate the ferric/ferrous ratio in 12 natural minerals.

Journal Article↗