Biomedical subjects

R Baumgartner

Publications and source records attributed to R Baumgartner.

At least 37 records · Page 2Linked to original sources

PubMed2001

Clinical experience with 5-aminolevulinic acid and photodynamic therapy for refractory superficial bladder cancer.

PURPOSE: We determined whether photodynamic therapy after the oral administration of 5-aminolevulinic acid in patients with superficial bladder cancer that cannot be controlled by transurethral resection and intravesical bacillus Calmette-Guerin (BCG) immunotherapy would preserve the bladder, while stopping tumor progression. Side effects of treatment were also assessed. MATERIALS AND METHODS: We performed photodynamic therapy after the oral administration of 5-aminolevulinic acid in 24 patients with rapidly recurring, multifocal, BCG refractory superficial pTa-pT1 transitional cell carcinoma of the bladder and carcinoma in situ. RESULTS: At a median followup of 36 months (range 12 to 51) 3 of the 5 patients with carcinoma in situ and 4 of the 19 with papillary tumors were free of recurrence. Three patients were rendered disease-free by repeat photodynamic therapy with 5-aminolevulinic acid and 3 underwent cystectomy. Tumor progression was stopped in 20 of our 24 cases. Immediately after the oral administration of 5-aminolevulinic acid hypotension and tachycardia occurred in 19 and 10 patients, respectively, with previously known severe cardiovascular disease. No phototoxic skin reaction or decreased bladder capacity was observed. CONCLUSIONS: These initial clinical results suggest that photodynamic therapy with orally administered 5-aminolevulinic acid is effective as an organ preserving procedure for treating superficial bladder cancer even in patients with bacillus Calmette-Guerin refractory carcinoma. One should be aware of hemodynamic instability after the oral administration of 5-aminolevulinic acid, particularly in patients with cardiovascular co-morbidity.

Adult↗

PubMed2001

Nutrition assessment in the elderly.

The prevalence of malnutrition, which is relatively low in free-living elderly persons (5-10%), is considerably higher (30-60%) in hospitalized or institutionalized elderly persons. As a result, nutritional assessment should be part of routine clinical practice in elderly patients who are frail, sick or hospitalized. A comprehensive screening tool for assessment of nutritional status is needed that is clinically relevant and cost-effective to perform. A number of simple and rapid tests for detecting or diagnosing malnutrition in the elderly have recently been developed. If malnutrition is suggested by such screening tests, then they should be supplemented by conventional nutritional assessment before treatment is planned.

Aged↗

PubMed2001

Photodynamic effects induced by aminolevulinic acid esters on human cervical carcinoma cells in culture.

Fluorescence diagnosis and photodynamic therapy using 5-aminolevulinic acid (ALA) provide new methods for the detection and treatment of cervical cancer and especially its precursors. However, these techniques are restricted by the rate of uptake of the hydrophilic ALA, its poor diffusion through the bilayer of biological membranes or both. In this study we evaluated the effect of some esterified ALA derivatives on the induction of the endogenous photosensitizer, protoporphyrin IX (PpIX), and the photodamage in cultured human cervical cells (C33-A and CaSki). The kinetics of PpIX accumulation showed that ALA esters, especially the ALA-hexylester (h-ALA), induced significantly faster PpIX formation than ALA at the same concentration (0.5 mM). The PpIX induction showed a dose-dependent characteristic. The highest PpIX values could be achieved by an up to 1.3-13-fold lower concentration of ALA esters than with ALA. Using the Annexin V assay, apoptosis was found to be induced rapidly after irradiation in both ALA- and ALA esters-treated cells. On measuring mitochondrial activity, the incubation with h-ALA induced a more pronounced photodamage. The results indicate that improved or at least comparable photodynamic effects can be achieved by using remarkably lower doses of ALA esters.

Aminolevulinic Acid↗

PubMed2001

Quantification of 5-aminolevulinic acid induced fluorescence improves the specificity of bladder cancer detection.

PURPOSE: 5-Aminolevulinic acid induced fluorescence endoscopy has outstanding sensitivity for detecting early stage bladder cancer. Nevertheless, a third of the lesions that show specific fluorescence are histologically benign. We decreased the false-positive rate of 5-aminolevulinic acid induced fluorescence endoscopy by incorporating protoporphyrin IX fluorescence quantification into the standard cystoscopy procedure. MATERIALS AND METHODS: In 25 cases (53 biopsies) of a history of or suspicion for bladder cancer 5-aminolevulinic acid induced fluorescence endoscopy and fluorescence image quantification were performed. For fluorescence image quantification images obtained with a target integrating color charge-coupled device camera were digitized and stored in a personal computer. Red-to-blue ratios were calculated from fluorescence positive lesions and results were correlated with hematoxylin and eosin histology. RESULTS: Malignant fluorescence positive lesions showed significantly stronger fluorescence intensity than fluorescing lesions with benign histology. A threshold was established that decreased the false-positive rate by 30% without affecting sensitivity. CONCLUSIONS: Fluorescence image quantification is a new endoscopic method for objectively selecting multicolor fluorescence bladder lesion images for biopsy. It has the potential of eliminating human error by different surgeons with variable experience in fluorescence endoscopy.

Adult↗

PubMed2000

Plasmid vaccine expressing granulocyte-macrophage colony-stimulating factor attracts infiltrates including immature dendritic cells into injected muscles.

Plasmid-encoded GM-CSF (pGM-CSF) is an adjuvant for genetic vaccines; however, little is known about how pGM-CSF enhances immunogenicity. We now report that pGM-CSF injected into mouse muscle leads to a local infiltration of potential APCs. Infiltrates reached maximal size on days 3 to 5 after injection and appeared in several large discrete clusters within the muscle. Immunohistological studies in muscle sections from mice injected with pGM-CSF showed staining of cells with the macrophage markers CD11b, Mac-3, IA(d)/E(d) and to the granulocyte marker GR-1 from day 1 through day 14. Cells staining with the dendritic cell marker CD11c were detected only on days 3 to 5. Muscles injected with control plasmids did not stain for CD11c but did stain for CD11b, Mac-3, IA(d)/E(d), and GR-1. No staining was observed with the APC activation markers, B7.1 or CD40, or with markers for T or B cells. These findings are consistent with the infiltrating cells in the pGM-CSF-injected muscles being a mixture of neutrophils, macrophages, and immature dendritic cells and suggest that the i.m. APCs may be enhancing immune responses to coinjected plasmid Ags. This hypothesis is supported by data showing that 1) separation of injections with pGM-CSF and Ag-expressing plasmid into different sites did not enhance immune responses and 2) immune enhancement was associated with the presence of CD11c+ cells in the infiltrates. Thus, pGM-CSF enhancement may depend on APC recruitment to the i.m. site of injection.

Adjuvants, Immunologic↗

PubMed2000

Photodetection of cervical intraepithelial neoplasia using 5-aminolevulinic acid-induced porphyrin fluorescence.

BACKGROUND: Screening for cervical carcinoma and its precursors is based on cervical cytology and diagnostic colposcopy. Despite the decrease in the incidence of cervical carcinoma in countries with a good screening program, this rate of decline is leveling off. Known problems are false-negative rates of cytology and low specificity of colposcopy. This clinical study examined the diagnostic potential of porphyrin fluorescence in patients with cervical intraepithelial neoplasia Grade 1-3 (CIN 1-3). METHODS: Sixty-eight women attending our colposcopy clinic underwent a gynecologic examination, including cytology, human papillomavirus (HPV) testing, and colposcopy. They received 10 mL 0.5% or 1.0% 5-aminolevulinic acid (5-ALA) topically. After 30-360 minutes, real-time image analysis was performed, and spectra were obtained from 685 sites. RESULTS: Due to rapid photobleaching, 0.5% 5-ALA proved ineffective for fluorescence assessment. Using 1% 5-ALA, the authors found that fluorescence intensities correlated with incubation time; however, fluorescence contrast showed a maximum at 60-90 minutes (ratio 11:1). HPV DNA positive lesions showed significantly higher fluorescence. Fluorescence imaging after 60-90 minutes achieved similar sensitivity and specificity compared with colposcopy in detecting CIN with 94% and 51% versus 95% and 50%, respectively. However, the specificity was markedly improved by fluorescence spectroscopy, achieving 75%. The evaluation of spectral measurements revealed significantly higher values for CIN compared with normal tissue and for CIN 2/3 compared with CIN 1 (P < 0.001). CONCLUSIONS: Using a time interval of 60-90 minutes after topical application of 1% 5-ALA, the authors observed specific porphyrin fluorescence of CIN. Fluorescence spectroscopy promises to become a valuable tool for the diagnosis of CIN.

Adult↗

PubMed2000

Solution structure of PCP, a prototype for the peptidyl carrier domains of modular peptide synthetases.

BACKGROUND: Nonribosomal peptide synthetases (NRPSs) are large modular enzymes responsible for the synthesis of a variety of microbial bioactive peptides. They consist of modules that each recognise and incorporate one specific amino acid into the peptide product. A module comprises several domains, which carry out the individual reaction steps. After activation by the adenylation domain, the amino acid substrate is covalently tethered to a 4'-phosphopantetheinyl cofactor of a peptidyl carrier domain (PCP) that passes the substrate to the reaction centres of the consecutive domains. RESULTS: The solution structure of PCP, a distinct peptidyl carrier protein derived from the equivalent domain of an NRPS, was solved using NMR techniques. PCP is a distorted four-helix bundle with an extended loop between the first two helices. Its overall fold resembles the topology of acyl carrier proteins (ACPs) from Escherichia coli fatty acid synthase and actinorhodin polyketide synthase from Streptomyces coelicolor; however, the surface polarity and the length and relative alignment of the helices are different. The conserved serine, which is the cofactor-binding site, has the same location as in the ACPs and is situated within a stretch of seven flexible residues. CONCLUSIONS: The structure of PCP reflects its character as a protein domain. The fold is well defined between residues 8 and 82 and the structural core of the PCP domain can now be defined as a region spanning 37 amino acids in both directions from the conserved serine. The flexibility of the post-translationally modified site might have implications for interactions with the cooperating proteins or NRPS domains.

Amino Acid Sequence↗

PubMed2000

Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid.

Photodynamic (PDT) therapy is a relatively new technique with unique properties that make it attractive for the local treatment of superficial epithelial disorders. The objective of this study was to investigate the clinical response of PDT with the photosensitizing agent 5-aminolevulinic acid (5-ALA) in patients with vulvar intraepithelial neoplasia (VIN) grades 1 to 3. Twenty-five patients with 111 lesions of VIN 1-3 were topically sensitized with 10 ml of a 20% solution of 5-ALA and treated with 57 cycles of laser light at 635 nm (100 J/cm(2)). Seventy (64%) of the 111 VIN lesions regressed after various PDT cycles. A complete response was achieved in 13 patients (52%) with 27 lesions. All patients with VIN 1 and mono- and bifocal VIN 2-3 showed complete clearance. However, a complete response could be achieved in only 4 (27%) of 15 women with multifocal VIN 2-3, whereas a partial response was noted in 9 of these patients with a total of 70 lesions, out of which 44 (63%) lesions disappeared. No response was seen in 2 patients with multifocal VIN 3. Histological assessment of the fluorescence-directed biopsies revealed that increased pigmentation and hyperkeratosis of the lesions were associated with low response rates. PDT using 5-ALA represents an alternative treatment modality for VIN which is easy to perform and has the advantage of minimal tissue destruction, low side effects and excellent cosmetic results. However, multifocal VIN disease with pigmented and hyperkeratinic lesions remains difficult to treat.

Adult↗

PubMed2000

Resampling as a cluster validation technique in fMRI.

Exploratory, data-driven analysis approaches such as cluster analysis, principal component analysis, independent component analysis, or neural network-based techniques are complementary to hypothesis-led methods. They may be considered as hypothesis generating methods. The representative time courses they produce may be viewed as alternative hypotheses to the null hypothesis, i.e., "no activation." We present here a resampling technique to validate the results of exploratory fuzzy clustering analysis. In this case an alternative hypothesis is represented by a cluster centroid. For both simulated and in vivo functional magnetic resonance imaging data, we show that by permutation-based resampling, statistical significance may be computed for each voxel belonging to a cluster of interest without parametric distributional assumptions.

Brain↗

PubMed2000

Diode laser treatment of hyperplastic inferior nasal turbinates.

UNLABELLED: Background and Objective Different laser types have been used for the treatment of hyperplastic inferior nasal turbinates. The clinical experiences of its treatment by means of a diode laser are presented. Study Design/Materials and Methods A total of 76 patients suffering from nasal obstruction due to hyperplastic inferior nasal turbinates were treated with a continuous diode laser (wavelength of lambda = 940 nm, laser parameter 10 W/energy/turbinate 5 kJ) in "noncontact" mode and under local anesthesia. All patients were refractory to conservative medical treatment. Fifty patients (26 of 50 [52%] with allergic rhinitis and 24 of 50 [48%] with vasomotor rhinitis) were included into this clinical trial with a follow-up of 1 year. The study was conducted by a questionnaire, photo documentation, allergy test, mucociliary clearance test, rhinomanometry, acoustic rhinometry, conventional radiology of the paranasal sinuses, and histology. RESULTS: The mean operation time took 6 min/turbinate, no nasal packing was necessary and no immediate complications (e.g., major bleeding) were observed. During the first 2-4 weeks, nasal obstruction was correlated to the extent of postoperative edema and nasal crusting. Statistical analysis revealed significant improvement of the nasal airflow (rhinomanometry) and nasal cavity volume (acoustic rhinometry) 6 months and 1 year after laser surgery, respectively. A total of 86% of the patients described a subjective improvement of nasal airflow 6 months and 76% of the patients 1 year after laser treatment. The mucociliary function test showed no significant variation in comparison to the preoperative measurements 1 year after laser treatment. CONCLUSION: Diode laser treatment of hyperplastic inferior nasal turbinates is a useful procedure, which can be performed as an outpatient surgery under local anesthesia, resulting in a controlled coagulation and ablation of the soft tissue. The short operation time and the good results provide an excellent patient acceptance.

Adolescent↗

PubMed2000

Correlator beware: correlation has limited selectivity for fMRI data analysis.

Groups of time-courses created from fMRI data by the frequently used correlation analysis are often highly heterogeneous. This heterogeneity is due to the limited selectivity of correlation when trying to match brain time-courses to an externally imposed activation paradigm. Thus, this process unnecessarily generates many type I errors (false positives). Furthermore, as a consequence of the heterogeneity, time-courses identified and grouped by correlation may in fact describe different activations. After demonstrating this inadequacy, we give one particular approach to partition such a heterogeneous group into internally more homogeneous subgroups, using Kendall's coefficient of concordance W, and show its applicability and application to both simulated and in vivo data. Such group partition and "purification" will help subsequent inferential methods to deal more efficiently with false positives.

Algorithms↗

PubMed2000

Initial experience in the treatment of oral leukoplakia with high-dose vitamin A and follow-up 5-aminolevulinic acid induced protoporphyrin IX fluorescence.

The aim of photodynamic diagnostics is complete visualization of all neoplastic lesions in a tumorous organ after the application of a tumor-selective photosensitizer. We explored the potential benefit of a combination of retinyl palmitate for the treatment of oral leukoplakias and follow-up diagnosis of malignant tissue by using 5-aminolevulinic acid (5-ALA) as a fluorescence marker. Semiquantitative measurements were performed following the topical application of 5-ALA in six patients. After biopsy and histological evaluation of tissue specimens the patients were treated with escalating doses of retinyl palmitate. After treatment periods ranging from 4 to 8 weeks 5-ALA was again applied for photodetection of persisting fluorescence. In all cases prior to retinyl palmitate treatment a prominent red fluorescence indicated tissue dysplasia. Eight weeks after treatment with retinyl palmitate decreased red fluorescence intensities were found, and repeated histological evaluations showed no persistent signs of dysplastic lesions. Our initial experience shows that high doses of retinyl palmitate can be useful for treating dysplastic lesions in the upper aerodigestive tract and can be monitored with 5-ALA induced protoporphyrin IX fluorescence.

Adult↗

PubMed2000

Spectrophotometric evaluation of the colour of intra- and subcutaneous bruises.

Spectrophotometric measurements were performed on intra- and/or subcutaneous bruises occurring in direct temporal connection with peracute fatal trauma. The purpose of these measurements was to determine whether the visual colour impression of a fresh traumatic extravasation can give information on the localisation of the haemorrhage in a certain tissue layer. After visual assessment of the colour of the bruise, the spectral reflectance curves and the CIE-L*a*b* colour values were determined with the help of a diode array spectrophotometer. The localisation and size of the haemorrhages in the cutis and/or subcutis were evaluated morphologically after incision of the skin. It was confirmed that there is a relationship between the colour impression and the localisation of the bruise. Bruises localised near the surface have a more reddish appearance while bruises in deeper layers give a more bluish colour impression. An explanation may be found in the optical characteristics of skin. Blood localised in the subcutis appears blue on the surface due to scattering processes in the dermis (Rayleigh scattering), as the blue wavelengths of the light are scattered (and thus reflected) to a greater extent than the red wavelengths.

Adolescent↗

PubMed2000

[Falls, frailty and osteoporosis in the elderly: a public health problem].

INTRODUCTION: Elderly people can be subdivided into three groups: healthy elderly persons (65-70% of the population), elderly subjects with diseases (about 5%) and frail old people. Frailty represents "age-related physiologic vulnerability resulting from impaired homeotasic stock and a reduced capacity of the organism to withstand stress". It could lead elderly subjects to pathological, barely reversible, ageing. CURRENT KNOWLEDGE AND KEY POINTS: One of the main objective of geriatricians is to develop useful screening tools to identify people at high risk, thus allowing them to benefit from preventive interventions as early as possible. It has been suggested that the decline in homeostatic stock involves numerous physiological systems. Those at the core of frailty would be neuromuscular changes resulting in sarcopenia, neuroendocrine dysregulation, and immune disorders. A recent study has shown that increased levels of interleukin 6 is a risk factor for frailty. FUTURE PROSPECTS AND PROJECTS: Work in progress aimed at identification of at-risk patients should: lead to early detection; draw attention on underestimated fields such as the nutritional status, sarcopenia, or gait disorders; promote the development of the standardized gerontological evaluation in order to identify the different components of frailty; and promote the development of non-pharmacological programmes including physical training, nutritional managing, and optimal social life.

Accidental Falls↗

PubMed2000

Artificial sweetener reduces nociceptive reaction in term newborn infants.

BACKGROUND: Sucrose has been shown to have an analgesic effect in preterm and term neonates. Sucrose, however, has a high osmolarity and may have deleterious effects in infants with fructose intolerance. Furthermore, it may favour caries. We therefore investigated the effects of a commercially available artificial sweetener (10 parts cyclamate and 1 part saccharin), glycine (sweet amino acid) or breast milk in reducing reaction to pain as compared with a placebo. SUBJECTS: Eighty healthy term infants, four days old, with normal birth weight. INTERVENTIONS: The infants were randomly assigned to one of four groups: 2 ml sweetener, glycine, expressed breast milk or water were given 2 min before a heel prick for the Guthrie test. The procedure was filmed with a video camera and analysed by two observers who did not know which medication the infant had received. RESULTS: Using a multivariate regression analysis, the following variables had significant correlation with relative crying time and recovery time: behavioural state before the intervention, the pricking nurse, and the type of medication. Relative crying time and recovery time were significantly less in the sweetener group but not in the glycine and the breast milk group. CONCLUSIONS: The artificial sweetener used in our study reduces pain reaction to a heel prick in term neonates, and thus provides an alternative to sucrose. In contrast, glycine tends to increase pain reaction whereas breast milk has no effect.

Analgesics↗

PubMed2000

Novelty indices: identifiers of potentially interesting time-courses in functional MRI data.

In a systematic study of hybrid MR time-series with simulated "activation" (contrast-to-noise range 1-10) we investigated the power and compared the ability of the "novelty indices" (NI) kurtosis, negentropy, and 1-lag autocorrelation, to discriminate between potentially interesting ("structured") and uninteresting ("noisy") time-courses (TCs). NIs may be employed as preprocessing tools to focus only on the interesting TCs prior to any further exploratory or confirmatory approach.

Humans↗

PubMed2000

Wavelet domain de-noising of time-courses in MR image sequences.

Magnetic resonance images acquired with high temporal resolution often exhibit large noise artifacts, which arise from physiological sources as well as from the acquisition hardware. These artifacts can be detrimental to the quality and interpretation of the time-course data in functional MRI studies. A class of wavelet-domain de-noising algorithms estimates the underlying, noise-free signal by thresholding (or 'shrinking') the wavelet coefficients, assuming the underlying temporal noise of each pixel is uncorrelated and Gaussian. A Wiener-type shrinkage algorithm is developed in this paper, for de-noising either complex- or magnitude-valued image data sequences. Using the de-correlation properties of the wavelet transform, as elucidated by Johnstone and Silverman, the assumption of i.i.d. Gaussian noise can be abandoned, opening up the possibility of removing colored noise. Both wavelet- and wavelet-packet based algorithms are developed, and the Wiener method is compared to the traditional Hard and Soft wavelet thresholding methods of Donoho and Johnstone. The methods are applied to two types of data sets. In the first, an artificial set of complex-valued images was constructed, in which each pixel has a simulated bimodal time-course. Gaussian noise was added to each of the real and imaginary channels, and the noise removed from the complex image sequence as well as the magnitude image sequence (where the noise is Rician). The bias and variance between the original and restored paradigms was estimated for each method. It was found that the Wiener method gives better balance in bias and variance than either Hard or Soft methods. Furthermore, de-noising magnitude data provides comparable accuracy of the restored images to that obtained from de-noising complex data. In the second data set, an actual in vivo complex image sequence containing unknown physiological and instrumental noise was used. The same bimodal paradigm as in the first data set was added to pixels in a small localized region of interest. For the paradigm investigated here, the smooth Daubechies wavelets provide better de-noising characteristics than the discontinuous Haar wavelets. Also, it was found that wavelet packet de-noising offers no significant improvement over the computationally more efficient wavelet de-noising methods. For the in vivo data, it is desirable that the groups of "activated" time-courses are homogeneous. It was found that the internal homogeneity of the group of time-courses increases when de-noising is applied. This suggests using de-noising as a pre-processing tool for both exploratory and inferential data analysis methods in fMRI.

Journal Article↗

PubMed2000

Comparison of two exploratory data analysis methods for fMRI: fuzzy clustering vs. principal component analysis.

Exploratory data-driven methods such as Fuzzy clustering analysis (FCA) and Principal component analysis (PCA) may be considered as hypothesis-generating procedures that are complementary to the hypothesis-led statistical inferential methods in functional magnetic resonance imaging (fMRI). Here, a comparison between FCA and PCA is presented in a systematic fMRI study, with MR data acquired under the null condition, i.e., no activation, with different noise contributions and simulated, varying "activation." The contrast-to-noise (CNR) ratio ranged between 1-10. We found that if fMRI data are corrupted by scanner noise only, FCA and PCA show comparable performance. In the presence of other sources of signal variation (e.g., physiological noise), FCA outperforms PCA in the entire CNR range of interest in fMRI, particularly for low CNR values. The comparison method that we introduced may be used to assess other exploratory approaches such as independent component analysis or neural network-based techniques.

Brain↗