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Biomedical subjects

C Burger

Publications and source records attributed to C Burger.

At least 37 records · Page 2Linked to original sources

Polymer-assisted formation of giant polyoxomolybdate structures.

A highly ordered, porous nanoscale network structure of polyoxomolybdate was prepared from the slow decomposition of an unstable precursor compound MoO(2)(OH)(OOH) in the presence of PEO-containing triblock copolymer gels or semidilute/concentrated poly(ethylene oxide) (PEO) homopolymer solutions. Small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXD) measurements of the 1-microm size crystals revealed an extremely ordered primitive cubic (pc) structure made of polyoxomolybdates. Scanning electron microscopy (SEM) measurements showed that the overall size of these single crystals was close to 1 microm, in agreement with estimates from the scattering peak widths. Evidence from both scattering measurements and transmission electron microscope (TEM) measurements suggested that the system formed a highly porous primitive cubic network similar to that of certain zeolite structures. However, the observed lattice constant of 5 nm was much larger. The function of the PEO-containing polymer network was found to be very subtle and complex. Presumably, PEO acted simultaneously as a weak reducing agent and as a viscous matrix to ensure sufficient time for the formation of long-range ordered structures, resulting in the growth of extremely uniform but probably hollow "nanospheres". We suggest that this new material may find unique applications as a high-efficiency absorbent or catalyst. Furthermore, the current synthetic method may open up new pathways to prepare similar functional nanomaterials.

Journal Article↗

Analysis of chord-length distributions.

A closed-form analytical solution for the inversion of the integral equation relating small-angle scattering intensity distributions of two-phase systems to chord-length distributions is presented. The result is generalized to arbitrary derivatives of higher order of the autocorrelation function and to arbitrary projections of the scattering intensity (including slit collimation). This inverse transformation offers an elegant way to investigate the impact of certain features, e.g. singularities, in the chord-length distribution or its higher-order derivatives on the scattering curve, e.g. oscillatory components in the asymptotic behavior at a large scattering vector. Several examples are discussed.

Journal Article↗

Regulation of neuronal traits by a novel transcriptional complex.

The transcriptional repressor, REST, helps restrict neuronal traits to neurons by blocking their expression in nonneuronal cells. To examine the repercussions of REST expression in neurons, we generated a neuronal cell line that expresses REST conditionally. REST expression inhibited differentiation by nerve growth factor, suppressing both sodium current and neurite growth. A novel corepressor complex, CoREST/HDAC2, was shown to be required for REST repression. In the presence of REST, the CoREST/HDAC2 complex occupied the native Nav1.2 sodium channel gene in chromatin. In neuronal cells that lack REST and express sodium channels, the corepressor complex was not present on the gene. Collectively, these studies define a novel HDAC complex that is recruited by the C-terminal repressor domain of REST to actively repress genes essential to the neuronal phenotype.

Animals↗

Spherical bilayer vesicles of fullerene-based surfactants in water: a laser light scattering study.

The low solubility of fullerenes in aqueous solution limits their applications in biology. By appropriate substitution, the fullerenes can be transformed into stabilized anions that are water soluble and can form large aggregated structures. A laser light scattering study of the association behavior of the potassium salt of pentaphenyl fullerene (Ph5C60K) in water revealed that the hydrocarbon anions Ph5C60- associate into bilayers, forming stable spherical vesicles with an average hydrodynamic radius and a radius of gyration of about 17 nanometers at a very low critical aggregation concentration of less than 10(-7) moles per liter. The average aggregation number of associated particles in these large spherical vesicles is about 1.2 x 10(4).

Journal Article↗

[Diagnosis of intra-articular fracture of the head of the tibia. A prospective comparative study].

Complete visualization of the joint surface is essential for correct assessment of tibial head fractures. Conventional tomography, computed tomography (CT), and magnetic resonance imaging (MRI) are compared in this prospective study. We examined 27 patients (19 suffering from B fractures and 8 from C fractures) from 1 January 1995 to 11 November 1998. Conventional tomography underestimated the fractures in 3 of the 19 cases of B fractures. Computed tomography underestimated two of these cases. MRI could not exactly depict the essential structures in three of the eight cases of C fractures because of edema and effusions. MRI identified complete cruciate ligament rupture in 6 of the 27 cases (18%) and 10 meniscal ruptures in 9 cases (33%: 6 medial meniscus, 4 lateral meniscus). Complete ruptures of the lateral collateral ligament were detected in five cases and medial collateral ligament ruptures in two cases. According to this, 63% of the patients suffered from relevant accompanying soft tissue injuries. The rate of soft tissue injuries increased up to 92% including the partial collateral ligament ruptures. Local hospital conditions permitting, X-ray-loaded conventional tomography should no longer be used in tibial head fractures. X-ray-free MRI is most efficient in cases of B fractures, which can in most cases be treated with a minimum of invasive techniques. Computed tomography is to be used in cases of C fractures that are regularly managed by open surgery accompanied by direct visualization of the inside of the knee joint.

Adult↗

Quantitative evaluation of skeletal tumours with dynamic FDG PET: SUV in comparison to Patlak analysis.

This study was carried out to evaluate bone lesions using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and to explore whether dynamic and quantitative PET data may help to differentiate benign lesions from malignant masses. Forty patients with primary bone lesions were studied. The final diagnosis was confirmed by histopathology. A 60-min dynamic FDG PET acquisition was undertaken in all subjects. From the dynamic PET images, indices such as the average and maximal standardised uptake values (SUVs), the tumour SUV-to-muscle SUV ratio (T/M) and the SUV at 60 min-to-SUV at 30 min ratio (averSUV60/30 min and maxSUV60/30 min) were produced. Patlak graphical analysis was used to obtain the influx constant (Ki), and the metabolic rate of FDG (MRFDG) was calculated. Based on the receiver operator characteristic curve, the sensitivity and specificity for each parameter in differentiating between malignant and benign lesions were evaluated. The histological results revealed 21 malignant tumours and 19 benign lesions in this group. The MRFDG and SUV indices in malignant lesions were significantly higher than those in benign lesions. However, each index showed a considerable overlap between benign and malignant lesions. Average SUV correlated positively with MRFDG (r=0.67). When a cut-off of 1.8 average SUV was used, the sensitivity and specificity for discrimination of malignancy from benign disease were 85% and 82.4%, respectively. MRFDG showed a similar sensitivity (82.4%) and a better specificity (92.9%). A combination consisting of a cut-off of average SUV (1.8) and averSUV60/30 min (1.1) resulted in an improvement of specificity to 93.3%, with a small reduction in sensitivity (81.3%) as compared with exclusive use of SUV. The results of this study indicate that a detectable difference in glucose metabolism exists between malignant and benign skeletal lesions. The static FDG uptake indices alone may not enable adequate differentiation between benign and malignant lesions. Quantitative dynamic imaging may provide more helpful information, but will not permit a definite diagnosis. The use of uptake indices may represent an alternative and interesting approach to the evaluation of bone lesions.

Adolescent↗

Isolation of a non-haemadsorbing, non-cytopathic strain of African swine fever virus in Madagascar.

African swine fever (ASF) suspected clinically in Madagascar (1998-9) was confirmed by polymerase chain reaction (PCR) and nucleotide sequencing, following virus isolation. No haemadsorption or cytopathic effect could be detected following leukocyte inoculation, but viral growth in cells was confirmed by PCR. Detection of ASF virus genome was carried out by amplification of a highly conserved region coding for the p72 protein. Nucleotide sequencing of the amplicon revealed 99.2% nucleotide identity between the recent Malagasy strains and a virus recovered from the 1994 outbreak in Mozambique (SPEC265). A serological survey performed on 449 sera, revealed that only 5.3% of the sera taken from pigs between 1998 and 1999 were positive.

African Swine Fever↗

Prospective multicenter evaluation of the morphometric D-score for prediction of the outcome of endometrial hyperplasias.

Prospective multicenter evaluation of the WHO classification and the morphometric D-score to predict endometrial hyperplasia cancer progression. In 132 endometrial hyperplasias WHO classification was performed by two experienced gynecologic pathologists. The D-score was assessed blindly by technicians in a routine diagnostic setting. Development of endometrial carcinoma during a 1-10-year follow-up was used as the end point. Eleven of 132 patients (8%), 10 of 61 (16%) atypical hyperplasias, and 1 of 71 (1%) nonatypical hyperplasias developed cancer. Twenty-six curettings had a D-score < or = 0 ("unfavorable" or endometrial intraepithelial neoplasia) of which 10 (38%) developed cancer. None of the 86 cases with a D-score > 1 ("favorable") and one of the 20 (5%) cases with 0 < D-score < or = 1 ("uncertain") developed cancer. Sensitivity of the D-score was 100%, specificity 82%, the positive and negative predictive values were 38% and 100%, respectively. These values are similar to those in three prior retrospective D-score studies but higher than the WHO values (which are 91%, 58%, 16%, and 99%, respectively). The D-score in endometrial hyperplasias is a more sensitive and specific marker for cancer prediction than the WHO classification, can be assessed in a routine clinical setting on standard hematoxylin and eosin sections (15-30 minutes per case), and is highly reproducible and cost-effective (U.S. $50 per case).

Adult↗

PET-CT-guided percutaneous puncture of an infected cyst in autosomal dominant polycystic kidney disease: case report.

An infected cyst in autosomal dominant polycystic kidney disease was identified with a combined positron emission tomographic (PET) and computed tomographic (CT) system, an experimental setup mimicking an integrated CT-PET scanner. Image fusion of fluorine 18 fluorodeoxyglucose PET and CT images allowed exact localization of the infected cyst among many cysts identified on previous CT and magnetic resonance images. Confirmation was obtained instantly, followed by CT-guided percutaneous puncture. Integrated imaging systems hold promise for direct PET-guided puncture of areas of increased fluorodeoxyglucose uptake by using the anatomic accuracy of CT.

Escherichia coli Infections↗

Quantitative PET studies in pretreated melanoma patients: a comparison of 6-[18F]fluoro-L-dopa with 18F-FDG and (15)O-water using compartment and noncompartment analysis.

UNLABELLED: The purpose of the study was to evaluate the 6-[18F]fluoro-L-dopa (FDOPA) kinetics with PET in patients with treated melanoma metastases and to compare it with the standard tracer 18F-FDG as well as with the perfusion tracer (15)O-water in selected cases. METHODS: The study included 11 patients (22 lesions) with pretreated metastatic melanomas. Dynamic studies with FDG and in selected cases with (15)O-water (eight patients) preceded the FDOPA study. A one-tissue-compartment model was used for the evaluation of the FDOPA and (15)O-water studies, and a two-tissue-compartment model and Patlak analysis were used for the FDG data. A noncompartment model based on chaos theory was used for calculating fractal dimension, which is a parameter for heterogeneity. RESULTS: The FDG studies showed a 1.5-fold increased uptake in comparison with surrounding tissue in 19 of 22 metastatic lesions (sensitivity of 86.4%). False-negative FDG results were obtained in 2 patients (three lesions). FDOPA uptake was enhanced in 14 of 22 metastatic lesions (sensitivity of 64%). FDG uptake was 1.5-fold higher than FDOPA uptake in 18 of 22 metastases from melanoma, whereas FDOPA uptake was 1.5-fold higher than FDG uptake in 2 patients with liver metastases. The data did not show a statistically significant correlation between the transport constant (K1) for FDOPA and that for FDG or between the standardized uptake value for FDOPA and FDG in metastases. No statistically significant correlation was found between K1 for FDOPA and that for (15)O-water. The data show that FDOPA uptake is not perfusion dependent and provides different information from FDG. The fractal dimension was similar for all tracers within the tumor region. Detectability of metastases was enhanced when both tracers were used (sensitivity of 95%). CONCLUSION: In patients with negative FDG findings, FDOPA can help to identify viable melanoma metastases and thus may help to select patients who would benefit from further treatment.

Dihydroxyphenylalanine↗

Efficacy of local versus systemic application of antibody-cytokine fusion proteins in tumor therapy.

Application of immunocytokines [fusion proteins (FuPs)] where the cytokine has been coupled to an antibody may not produce the severe side effects frequently observed during systemic application of cytokines in cancer therapy. However, it has not been explored whether FuPs are sufficient for intratumoral activation of leukocytes or whether intratumoral versus systemic application may be of greater efficacy. Interleukin 2 (IL2) or tumor necrosis factor (TNF) coupled to an anti-epidermal growth factor receptor monoclonal antibody (IL2-FuP or TNF-FuP) were tested in SCID mice bearing a human epidermal growth factor receptor-positive melanoma transplant and being reconstituted with human HLA-matched peripheral blood leukocytes. Whole-body autoradiography revealed larger accumulation and prolonged retention of i.v. or intratumorally applied IL2-FuP or TNF-FuP compared with the antibody. Even with low doses of FuP, tumor growth was significantly retarded, with the survival time being further prolonged by the intratumoral application. Furthermore, outgrowth of the tumor was prevented in approximately 50% of mice as long as they received weekly injections of peripheral blood leukocytes concomitantly with the FuPs, which confirmed that it was the donor leukocytes activated in vivo that retarded tumor growth. An in vitro analysis revealed that the IL2-FuP supported mainly proliferation and lymphokine-activated killer cell activity, whereas TNF-FuP stimulated cytokine production and cytotoxic activity of monocytes and, to a low degree, of T cells. Both TNF-FuP and IL2-FuP significantly accumulated in the tumor, which led to retardation of tumor growth. The therapeutic effect was improved by intratumoral application. Importantly, the efficacy of both IL2-FuP and TNF-FuP depended on the induction of an immune response in vivo.

Animals↗

Dynamic PET 18F-FDG studies in patients with primary and recurrent soft-tissue sarcomas: impact on diagnosis and correlation with grading.

UNLABELLED: The purpose of this study was to evaluate (18)F-FDG PET studies of primary and recurrent sarcomas for diagnosis and correlation with grading. METHODS: The evaluation included 56 patients, 43 with histologically proven malignancies and 13 with benign lesions. Seventeen patients were referred with suspicion on a primary tumor, and the remaining 39 were referred with suspicion on a recurrent tumor. The FDG studies were accomplished as a dynamic series for 60 min. The evaluation of the FDG kinetics was performed using the following parameters: standardized uptake value (SUV), global influx, computation of the transport constants K1-k4 with consideration of the distribution volume (VB) according to a two-tissue-compartment model, and fractal dimension based on the box-counting procedure (parameter for the inhomogeneity of the tumors). RESULTS: Visual evaluation revealed a sensitivity of 76.2%, a specificity of 42.9%, and an accuracy of 67.9%. The vascular fraction VB and the SUV were higher in malignant tumors compared with benign lesions (t test, P < 0.05). Although the FDG SUV helped to distinguish benign and malignant tumors, there was some overlap, which limited the diagnostic accuracy. The SUV and fractal dimension accounted for significant differences in six of the nine diagnostic pairs. Whereas grade (G) II and G III tumors were differentiated from lipomas on the basis of the fractal dimension and some other kinetic parameters, no differences were found between G I tumors and lipomas. On the basis of the discriminant analysis, the differentiation of soft-tissue tumors was best for the use of six parameters of the FDG kinetics (SUV, VB, K1, k3, influx, and fractal dimension). Eighty-four percent of G III tumors, 37.5% of G II tumors, 80% of G I tumors, 50% of lipomas, and 14.3% of scars could be classified correctly, whereas inflammatory lesions were misclassified. CONCLUSION: FDG PET should be used preferentially for monitoring patients with G III sarcomas. Visual analysis provides a low specificity. In contrast, the evaluation of the full FDG kinetics provides superior information, particularly for the discrimination of G I and G III tumors (positive predictive value, >80%).

Diagnosis, Differential↗

Interleukin 2-antibody and tumor necrosis factor-antibody fusion proteins induce different antitumor immune responses in vivo.

Two fusion proteins, composed of interleukin 2 (IL-2) or tumor necrosis factor (TNF) coupled to an antibody [fusion protein (FuP); IL-2-FuP or TNF-FuP], were capable of retarding growth of a human malignant melanoma in the severe combined immunodeficient mouse depending on the concomitant application of human peripheral blood leukocytes. Here we have analyzed the mechanisms that determine the therapeutic effect. Tumor-bearing severe combined immunodeficient mice received once per week an i.v. injection of HLA-matched peripheral blood leukocytes and twice per week i.v. or intratumoral injections of FUPS: Leukocyte recovery and their activation state were monitored. The number of draining lymph node cells (LNCs) and tumor-infiltrating leukocytes increased continuously, and the yield of draining LNCs was improved significantly when the FuPs were applied locally. In IL-2-FuP-treated mice, the majority of draining LNCs and tumor-infiltrating lymphocytes expressed T-cell activation markers and IL-2, thus being classified as T helper type 1 cells. These cells displayed strong proliferative activity and initiated activation of lymphokine-activated killer cells and CTLS: TNF-FuP supported activation of CTLs and of monocytes as revealed by TNF expression and cytostatic activity. Neither the antibody, nor IL-2, nor TNF, nor the mixture of antibody and cytokines exhibited the full-fledged activational potency of the FUPS: Notably, activation of immune effector mechanisms was much stronger when the FuPs were applied intratumorally. This is the first report to show that FuPs are efficient immunostimulants in vivo for native leukocytes. Although IL-2-FuP induced a T helper type 1 response with recruitment of LAK and CTL, TNF-FuP efficiently recruited and activated monocytes and, in a less pronounced manner, CTLS:

Animals↗

[Spinal injuries in jockeys. 2 case reports and review of the literature].

Two cases of severe spinal cord injuries to professional horse-racing jockeys are presented. There is only one comprehensive study conducted to ascertain the nature and incidence of injuries in the literature. The pathomechanism and surgical therapy of vertebral trauma in jockeys was analysed.

Accidental Falls↗

Simplified quantitative determination of cerebral perfusion reserve with H2(15)O PET and acetazolamide.

The measurement of regional cerebral blood flow (rCBF) and perfusion reserve (PR) with H2(15)O positron emission tomography (PET) and acetazolamide challenge is of importance in evaluating patients with cerebrovascular disease and is thought to be useful in selecting patients for possible vascular surgery. Full quantitative assessment of rCBF with PET requires arterial blood sampling, which is inconvenient in a clinical setting. In this work, we present a simple non-invasive method with which to quantitatively evaluate PR in one PET session lasting no more than 30 min. In ten patients with cerebrovascular disease, rCBF was measured with H2(15)O PET under the baseline condition and after administration of 1 g acetazolamide using a standard technique involving arterial blood sampling. The activity accumulated over 60 s was normalized to injected activity per kilogram body weight (nAA) and compared with rCBF in eight different brain regions. A high linear correlation was found for PR based on nAA (PRnAA) and rCBF (PRrCBF) (PRnAA=0.843 PRrCBF + 0.092, r=-0.83, Pearson's correlation coefficient). Bland-Altman analyses further confirmed that PRnAA reflects PR in a quantitative manner. These results demonstrate that the method based on normalized counts allows the quantitative assessment of PR without blood sampling.

Acetazolamide↗

Evaluation of serotonergic transporters using PET and [11C](+)McN-5652: assessment of methods.

[11C](+)McN-5652 is an established positron emission tomography tracer used to assess serotonergic transporter density. Several methods have been used to analyze [11C](+)McN-5652 data; however, no evaluation of candidate methods has been published in detail yet. In this study, compartmental modeling using a one-tissue compartment model (K1, k2"), a two-tissue compartment model (K1 to k4), and a noncompartmental method that relies on a reference region devoid of specific binding sites were assessed. Because of its low density of serotonergic transporters, white matter was chosen as reference. Parameters related to transporter density were the total distribution volume DV" (= K1/k2", one tissue compartment), DVtot, (=K1/k1' (1 + k3/k4), two tissue compartments), and Rv (= k3'/k4, noncompartmental method). The DV", DVtot, and Rv values extended over a similar range and reflected the known pattern of serotonergic transporters. However, all parameters related to transporter density were markedly confounded by nonspecific binding. With regard to K1, the one-tissue compartment model yielded markedly lower values, which were, however, more stable. The minimal study duration needed to determine stable values for the distribution volume was approximately 60 minutes. The choice of the method to analyze [11C](+)McN-5652 data depends on the situation. Parametric maps of Rv are useful if no information on K1 is needed. If compartmental modeling is chosen, both the one- and the two-tissue compartment models have advantages. The one-tissue compartment model underestimates K1 but yields more robust values. The distribution volumes calculated with both models contain a similar amount of information. None of the parameters reflected serotonergic transporter density in a true quantitative manner, as all were confounded by nonspecific binding.

Adult↗

Cerebral embolization presenting as delayed, severe obtundation in the postanesthesia care unit after total hip arthroplasty.

Catastrophic neurologic events occur rarely postoperatively and must be diagnosed quickly. A 63-year-old woman who had undergone uneventful total hip arthroplasty experienced obtundation after admission to the postanesthesia care unit. Cranial magnetic resonance imaging revealed multiple lesions consistent with ischemia or infarction, and fat cerebral embolism was diagnosed. We describe the numerous complications that may occur in patients in the postanesthesia care unit and review the differential diagnosis of altered mental status in such patients. Paradoxical cerebral fat embolization must be considered in the differential diagnosis of altered mental status after pelvic or long bone fracture or lower extremity major joint replacement, and this condition may occur despite normal pulmonary function and no patent foramen ovale or right-to-left intracardiac shunt. Magnetic resonance imaging with T2-weighted sequences is the cranial imaging study of choice for early evaluation of patients with sudden multifocal neurologic deficits and suspected fat embolism syndrome.

Anesthesia Recovery Period↗

Kinetic and equilibrium analyses of [(123)I]epidepride binding to striatal and extrastriatal dopamine D(2) receptors.

Quantitative SPECT measures of dopamine D(2) like receptors with [(123)I]epidepride is complicated by its high affinity and lipophilic metabolites. The purpose of this study was to use both parent (P) and lipophilic metabolites (M) as input functions in a kinetic paradigm and in comparison to the results of equilibrium studies. Kinetic studies on eleven healthy human subjects, ages 32+/- 10 were performed following i.v. injection of approximately 370 MBq of [(123)I]epidepride. Images were acquired for 13.5+/-1.0 hours. Equilibrium studies were done on seven of eleven subjects with a bolus injection of approximately 140 MBq, bolus/infusion ratio of 10 hours, and infusion for 30-32 hours. High (striatum) and low (temporal cortex) density regions were studied. Two (P and M) and one (P) input function models were applied in the kinetic studies. In receptor-rich regions, the distribution volumes in nondisplaceable compartments were fixed to those in cerebellum. In addition, in the two input function model, K(1)(P)/K(1)(M) was fixed to the values in the cerebellum. The one input function model provided V'(3) values (=f(1)*B'(max)/K(D)) which were consistent with those obtained in equilibrium studies in both receptor-rich regions, while the two input function model provided consistent values only in striatum. Poor identifiability of the rate constants of metabolites seemed to be the source of errors in the two input function model. These results suggest that correct V'(3) values can be obtained with the one input function model both in high- and low-density regions.

Adult↗