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Biomedical subjects

R Baumgartner

Publications and source records attributed to R Baumgartner.

At least 55 records · Page 3Linked to original sources
PubMed2000

A wavelet-based method for improving signal-to-noise ratio and contrast in MR images.

Magnetic resonance (MR) images acquired with fast measurement often display poor signal-to-noise ratio (SNR) and contrast. With the advent of high temporal resolution imaging, there is a growing need to remove these noise artifacts. The noise in magnitude MR images is signal-dependent (Rician), whereas most de-noising algorithms assume additive Gaussian (white) noise. However, the Rician distribution only looks Gaussian at high SNR. Some recent work by Nowak employs a wavelet-based method for de-noising the square magnitude images, and explicitly takes into account the Rician nature of the noise distribution. In this article, we apply a wavelet de-noising algorithm directly to the complex image obtained as the Fourier transform of the raw k-space two-channel (real and imaginary) data. By retaining the complex image, we are able to de-noise not only magnitude images but also phase images. A multiscale (complex) wavelet-domain Wiener-type filter is derived. The algorithm preserves edges better when the Haar wavelet rather than smoother wavelets, such as those of Daubechies, are used. The algorithm was tested on a simulated image to which various levels of noise were added, on several EPI image sequences, each of different SNR, and on a pair of low SNR MR micro-images acquired using gradient echo and spin echo sequences. For the simulated data, the original image could be well recovered even for high values of noise (SNR approximately 0 dB), suggesting that the present algorithm may provide better recovery of the contrast than Nowak's method. The mean-square error, bias, and variance are computed for the simulated images. Over a range of amounts of added noise, the present method is shown to give smaller bias than when using a soft threshold, and smaller variance than a hard threshold; in general, it provides a better bias-variance balance than either hard or soft threshold methods. For the EPI (MR) images, contrast improvements of up to 8% (for SNR = 33 dB) were found. In general, the improvement in contrast was greater the lower the original SNR, for example, up to 50% contrast improvement for SNR of about 20 dB in micro-imaging. Applications of the algorithm to the segmentation of medical images, to micro-imaging and angiography (where the correct preservation of phase is important for flow encoding to be possible), as well as to de-noising time series of functional MR images, are discussed.

Algorithms↗
PubMed2000

Structure of a novel leech carboxypeptidase inhibitor determined free in solution and in complex with human carboxypeptidase A2.

Leech carboxypeptidase inhibitor (LCI) is a novel protein inhibitor present in the medicinal leech Hirudo medicinalis. The structures of LCI free and bound to carboxypeptidase A2 (CPA2)have been determined by NMR and X-ray crystallography, respectively. The LCI structure defines a new protein motif that comprises a five-stranded antiparallel beta-sheet and one short alpha-helix. This structure is preserved in the complex with human CPA2 in the X-ray structure, where the contact regions between the inhibitor and the protease are defined. The C-terminal tail of LCI becomes rigid upon binding the protease as shown in the NMR relaxation studies, and it interacts with the carboxypeptidase in a substrate-like manner. The homology between the C-terminal tails of LCI and the potato carboxypeptidase inhibitor represents a striking example of convergent evolution dictated by the target protease. These new structures are of biotechnological interest since they could elucidate the control mechanism of metallo-carboxypeptidases and could be used as lead compounds for the search of fibrinolytic drugs.

Amino Acid Sequence↗
PubMed2000

Assessment of 5-aminolevulinic acid-induced porphyrin fluorescence in patients with peritoneal endometriosis.

OBJECTIVE: The purpose of this study was to examine the diagnostic potential for patients with endometriosis of porphyrin fluorescence after oral administration of 5-aminolevulinic acid. STUDY DESIGN: Fifteen women referred for laparoscopy because of suspected endometriosis received 1 or 10 mg/kg 5-aminolevulinic acid orally. After 1.5 to 6 hours endoscopic fluorescence spectral analysis and video inspection were performed. RESULTS: With 10 mg/kg 5-aminolevulinic acid and application intervals of >3 hours we observed a significantly higher porphyrin fluorescence in active peritoneal endometriosis than in adjacent normal peritoneum. Pigmented and nodular endometriosis showed weak to negative fluorescence. A strong fluorescence of the fimbrial mucosa was seen. A 1-mg/kg dose of 5-aminolevulinic acid was insufficient for fluorescence diagnosis. No side effects were recorded. CONCLUSION: Porphyrin fluorescence after oral administration of 5-aminolevulinic acid may be beneficial in diagnosis of peritoneal endometriosis. The strong fluorescence of fimbrial mucosa may limit the applicability of this technique in young women, however, because phototoxic damage cannot be excluded at present.

Adult↗
PubMed2000

Detection of squamous cell carcinoma of the oral cavity by imaging 5-aminolevulinic acid-induced protoporphyrin IX fluorescence.

OBJECTIVES: Early cancer detection is the best way to improve the prognosis of patients with oral cancer. Therefore this study presents quantitative fluorescence measurements and results in the visualization of cancerous oral mucosa with 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX). METHODS: Time progression and type of porphyrin accumulation were analyzed in neoplastic and surrounding healthy tissue of 58 patients with a suspected cancer of the oral cavity by measuring emission spectra of 5-ALA-induced PPIX fluorescence. Fluorescence images in the red and green spectral range from the tumor tissue were recorded with a charge-coupled device camera. RESULTS: After topical application of 0.4% 5-ALA and incubation for 1 to 2.5 hours, all patients revealed higher intensities of red fluorescence in neoplastic tissue compared with the surrounding normal tissue. Maximum contrast was reached after 1.5 hours of incubation. In 13.8% (n = 8) of the patients, additional findings like dysplasia, carcinoma in situ, primary tumor, secondary carcinomas, and tumor branches were found by means of fluorescence marking in contrast to white light examination. An evaluation of the biopsy specimens resulted in a specificity of 60% and a sensitivity of 99%. CONCLUSIONS: As a fluorescent marker, PPIX could represent a possible new diagnostic tool to detect early malignant and secondary lesions in the oral cavity. In addition, 5-ALA-induced PPIX fluorescence is promising as a useful intraoperative tool for determining adequate surgical margins of resection. Further investigations aim to assess this diagnostic procedure as a sensitive and clinically reliable method for patients with oral cancer.

Adult↗
PubMed1999

Photodynamic therapy in women with cervical intraepithelial neoplasia using topically applied 5-aminolevulinic acid.

Photodynamic therapy (PDT) is a novel treatment modality that produces local tissue necrosis with laser light after prior administration of a photosensitizing agent. We performed a study of topically applied 5-aminolevulinic acid (5-ALA) in the photodynamic treatment of women with high-grade cervical intraepithelial neoplasia (CIN) using fixed 5-ALA doses and application protocols derived from previous in vitro and in vivo results. Three to 5 hr prior to PDT, 10 ml of a 20% solution of 5-ALA was topically applied using a cervical cap. PDT was performed with irradiation of 100 J/cm2 at an irradiance of 100-150 mW/cm2 with an argon-ion-pumped dye laser at 635 nm. For the endocervix, a specifically designed cylindrical applicator was used. Ten treatment cycles of PDT using 5-ALA were performed in 7 patients with high-grade CIN. Non-thermal laser treatment with 100-150 mW/cm2 was well tolerated. Local toxicity was minor as several patients reported burning sensations and vaginal discharge, but no necrosis, sloughing or scarring occurred. After 3 months, a significant reduction in the size of the ectocervical CIN lesions was noted in only 3 patients, who underwent a second PDT cycle. However, no significant improvement in CIN lesions was noted since cold knife conization revealed persistent CIN in all 7 cases. Therefore, PDT after topical application of 5-ALA using an irradiation of 100 J/cm2 produces only minimal side effects. However, it does not appear to be effective in treating CIN.

Administration, Topical↗
PubMed1999

The domains of protein S from Myxococcus xanthus: structure, stability and interactions.

Protein S from Myxococcus xanthus is a member of the beta gamma-crystallin superfamily. Its N and C-terminal domains (NPS and CPS, respectively) show a high degree of structural similarity and possess the capacity to bind two calcium ions per domain. For NPS, their positions were determined by X-ray diffraction at 1.8 A resolution, making use of molecular replacement with the NMR structure as search model. The overall topology of NPS is found to be practically the same as in complete protein S. In natural protein S, the domains fold independently, with a significant increase in stability and cooperativity of folding in the presence of Ca2+. The recombinant isolated domains are stable monomers which do not show any tendency to combine to "nicked" full-length protein S. In order to investigate the stability and folding of natural protein S and its isolated domains, spectroscopic techniques were applied, measuring the reversible urea and temperature-induced unfolding transitions at varying pH. The increment of Ca2+ to the free energy of stabilization amounts to -10 and -5 kJ/mol for NPS and CPS, respectively. For both NPS and CPS, in the absence and in the presence of 3 mM CaCl2, the two-state model is valid. Comparing DeltaGU-->N for CPS (-21 kJ/mol at pH 7, liganded with Ca2+) with its increment in the intact two-domain protein, the stability of the isolated domain turns out to be decreased in a pH-dependent manner. In contrast, the stability of Ca2+-loaded NPS (DeltaGU-->N=-31 kJ/mol, pH 7) is nearly unchanged down to pH 2 where Ca2+ is released (DeltaGU-->N=-26 kJ/mol, pH 2). In intact protein S, the N-terminal domain is destabilized relative to NPS. Evidently, apart from Ca2+ binding, well-defined domain interactions contribute significantly to the overall stability of intact protein S.

Bacterial Proteins↗
PubMed1999

Effects on the mitosis of normal and tumor cells induced by light treatment of different wavelengths.

OBJECTIVE: Although the background of laser therapy by means of low level energy and power is still only partially understood, there are nevertheless promising reports from clinical studies concerning pain treatment, the acceleration of wound healing, and the modulation of cell functions. In order to contribute to the understanding of such a phototherapeutic procedure cell experiments were performed. MATERIALS AND METHODS: The influence of light (lambda = 410, 488, 630, 635, 640, 805, and 1,064 nm and broad band white light) on the proliferation of cells was investigated on skeletal myotubes (C2), normal urothelial cells (HCV29), human squamous carcinoma cells of the gingival mucosa (ZMK1), urothelial carcinoma cells (J82), glioblastoma cells (U373MG), and mamma adenocarcinoma cells (MCF7) in a computer-controlled light treatment chamber. The cellular response was tested by way of the following methods: The rate of mitosis was determined by counting the single cells after Orcein-staining. The proliferation index measurements were based on the BrdU incorporation during the DNA synthesis. Statistics were performed using unpaired Student's t-test procedures, stating P < 0. 05 to be significant and P>0.05 not to be significant. RESULTS: Twenty-four hours after light treatment, a significant increase in the mitotic rate of J82 and HCV29 cells was determined when illuminated with lambda = 410 nm, lambda = 635 nm and lambda = 805 nm, respectively. C2 cells showed an increase only after lambda = 635 nm illumination. In all three cell lines, a maximum mitotic rate was determined after an irradiation between 4 and 8 J/cm(2), while a reduced mitotic rate was measured at 20 J/cm(2). MCF7, U373MG, and ZMK1 cells showed a slight decrease in the mitotic rate with increasing irradiation independent of the wavelength used. When an irradiation of 20 J/cm(2) was applied, all cell lines showed a slight decrease compared to the controls independent to the wavelength used. White light as well as lambda = 1,064 nm does not affect the mitotic rate in this irradiation range. No significant differences in the effects could be determined when the irradiance changed between 10 and 150 mW/cm(2) at certain irradiation values. The BrdU test did not show any significant alterations with respect to possible light induced processes compared to the controls. CONCLUSIONS: Dependent upon the irradiation parameter, light of a defined wavelength does affect the mitotic rate of both normal as well as tumor cells. It could be hypothesized that the action spectra of the cellular response indicate the participation of endogenous porphyrins and cytochromes as primary photoreceptors. Taking into account all light induced processes, the term biomodulation should preferably be used.

DNA↗
PubMed1999

Autofluorescence imaging and spectroscopy of normal and malignant mucosa in patients with head and neck cancer.

BACKGROUND AND OBJECTIVE: An early detection of oral cancer might improve the patient's prognosis. We present preliminary results of autofluorescence photodetection of cancerous oral mucosa. MATERIALS AND METHODS: 49 patients were investigated altogether. In 30 patients, malignant and healthy oral mucosa were excited with violet light (lambda = 375 to 440 nm). Images were recorded by a sensitive CCD camera. Spectrophotometric analysis in the green spectral range was performed on tumorous and innocuous mucosa in 36 patients. RESULTS: In 13 patients (43.3%), tumors were subjectively better distinguishable from their surroundings through a reduction of green autofluorescence than by ordinary inspection. Tumor detection abilities varied for different locations and tumor morphologies. Spectral analysis showed contrasts in autofluorescence intensities between tumor and normal tissues in 34 patients (94.4%). Autofluorescence spectra of normal mucosa varied both inter- and intraindividually. CONCLUSIONS: Using violet excitation light, camera-based autofluorescence photodetection in the green spectral range presented a highly promising tool for the diagnosis of oral malignomas in almost half of the cases examined. The possible ways on how the obtained results could serve to find a more advanced method for a precise tumor detection in the oral cavity are being discussed.

Adult↗
PubMed1999

Fluorescence staining of laryngeal neoplasms after topical application of 5-aminolevulinic acid: preliminary results.

BACKGROUND AND OBJECTIVE: The prognosis of patients suffering from laryngeal carcinomas can be improved by early diagnosis. Exact demarcation of tumor margins could contribute to an optimum preservation of the larynx. Therefore, the aim of the present study was the evaluation of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence as a new diagnostic procedure for the detection of laryngeal cancer. STUDY DESIGN/MATERIALS AND METHODS: Sixteen patients with suspected malignancies of the larynx received 0.6 wt% 5-ALA-NaCl solution by means of a medical nebulizer. After a period of 1-2 hours, the patients underwent microlaryngoscopy under white light and fluorescence illumination (lambda(ex) = 375-440 nm). A quantitative analysis of the fluorescence contrast between neoplastic and surrounding tissue was performed using an optical multichannel analyzer. RESULTS: Carcinoma, carcinoma in situ, and dysplasia showed red fluorescence that could be attributed to the 5-ALA-induced formation of PPIX. The surrounding normal tissue exhibited autofluorescence in the green spectral range, which was greatly reduced within the tumor. The results of macroscopic red fluorescence staining were correlated with the histologic diagnosis. CONCLUSION: According to these preliminary results, the presented method seems to be a promising adjunct diagnostic procedure for the early identification of malignant neoplasms in the larynx. The aim of further investigations is the assessment of sensitivity and specificity and an evaluation of fluorescence-guided laser resections of laryngeal cancer. Lasers Med. Surg. 25:414-420, 1999.

Administration, Topical↗
PubMed1999

Neuroleptic malignant syndrome during low dosed neuroleptic medication in first-episode psychosis: a case report.

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal side-effect of antipsychotic drug therapy, especially of dopamine receptor antagonists. As a dose relationship has been postulated, low dose neuroleptization would be expected to help to avoid this side-effect. In contrast, we report on a 21-year-old female following low dose fluphenazine treatment with 2.5 mg/day. The patient recovered from NMS after 3 days of dantrolene administration. Eventually, remission from psychotic symptoms was achieved with clozapine. At 8-month follow-up, psychopathology remained stable and there were no more signs of NMS.

Adult↗
PubMed1999

The site of atheromatosis in the subclavian and vertebral arteries and its implication for angioplasty.

We analysed the site of plaques and stenoses in the subclavian and vertebral arteries, to improve the safety of percutaneous transluminal angioplasty (PTA) in high-risk patients. These lesions were assessed on arteriograms of 35 patients with stenoses and occlusions of the subclavian and vertebral arteries; the degree of stenoses was measured. Of 19 subclavian artery stenoses 17 (89%) were in the segment proximal to the vertebral artery; 30 (79%) of 38 vertebral artery stenoses were on the medial wall. With this knowledge, a double-balloon technique using a simultaneous transbrachial and transfemoral approach for angioplasty of high-risk subclavian or combined subclavian and vertebral artery stenoses and occlusions was used successfully in seven patients. This new technique may broaden the endovascular therapeutic possibilities in the rare but dangerous situation where plaque extends directly from the stenotic subclavian artery into the origin of the vertebral artery.

Aged↗
PubMed1999

Detection of colonic dysplasia by light-induced fluorescence endoscopy: a pilot study.

Light-induced fluorescence endoscopy (LIFE) has been shown to differentiate between normal mucosa and dysplastic lesions, and dysplastic lesions of the colon occult to routine white-light colonoscopy may thus be visualized by LIFE. We compared the sensitivity and specificity of LIFE to routine white-light colonoscopy in patients with colonic dysplasia. In a pilot study 20 patients with colonic adenoma, inflammatory bowel disease, or with a history of colon cancer were screened for colonic dysplasia during routine colonoscopy. Forty-two sites of mucosal abnormalities regarded as suspicious for dysplasia during white-light colonoscopy were additionally examined with a prototype LIFE system. Biopsies were taken from all 42 colonic sites. The LIFE images were classified as positive or negative for dysplasia. Sensitivity and specificity were calculated by correlating positive and negative findings to the histopathological results. Histopathology detected 21 adenomas with low-grade dysplasia and one with high-grade dysplasia. All dysplastic lesions were found by routine white-light endoscopy. The specificity of conventional white-light endoscopy was 80%. Of the 22 dysplastic lesions 20 were detected by LIFE (sensitivity 91%). The specificity of LIFE was 90% (two false-positive results). LIFE combined with conventional endoscopy may thus improve the detection of colonic dysplasia.

Adult↗
PubMed1999

Longitudinal changes in serum 25-hydroxyvitamin D in older people.

Cross-sectional studies have suggested that serum 25-hydroxyvitamin D (25OHD) levels decline with aging. We have examined this putative decline in a longitudinal study using participants in the New Mexico Aging Process Study. 25OHD levels were measured in participants in whom serum samples were available between 1980 to 1982 and 1989 to 1994 (37 men and 99 women). The available data for these visits included age, gender, and the date the sample was obtained. Questionnaires assessing physical activity and vitamin D intake were administered at the visits. A seasonal variation (r = .25, P < .05) in 25OHD was demonstrated in the whole group of subjects. In 25 subjects who were not receiving vitamin D supplementation at either time and had samples obtained in the same season, both serum 25OHD (P < .05) and physical activity (P < .05) decreased over a mean period of 11.4 years. In 23 subjects who had samples obtained in the same season but used vitamin D supplements at both times, there was no change in serum 25OHD. Mean summer 25OHD levels did not change with the duration of study. On the other hand, the mean serum 25OHD declined with the duration of study when measured from winter to winter or spring to spring. Multiple regression analysis demonstrated that the month, activity level, vitamin D supplementation, and gender (P < .001) were independent determinants of serum 25OHD levels. This study confirms that aging is associated with a reduction in serum 25OHD, and suggests that this decrease is a reflection of reduced sun exposure rather than aging per se. The reduction in serum 25OHD was the result of decreasing winter and spring 25OHD serum concentrations. It is clear that vitamin D supplementation can prevent the age-related decline in 25OHD levels.

Aged↗
PubMed1999

Photodynamic therapy of vulvar lichen sclerosus with 5-aminolevulinic acid.

OBJECTIVE: To evaluate the therapeutic effect of photodynamic therapy on vulvar lichen sclerosus. METHODS: Twelve women with lichen sclerosus were enrolled in a prospective, single-arm pilot study. Four to 5 hours before photodynamic therapy, 10 mL of a 20% solution of 5-aminolevulinic acid was applied topically to the vulva. Photodynamic therapy was administered with an irradiation of 80 J/cm2 at an irradiance of 40-70 mW/cm2. Light with a wavelength of 635 nm was delivered by an argon ion-pumped dye laser. The degree of pruritus was evaluated using a horizontal visual analog scale before and after 6-8 weeks, and patients were followed tri-monthly after photodynamic therapy. RESULTS: Two women underwent two cycles of photodynamic therapy, one underwent three cycles, and the remaining nine women underwent one cycle each. Treatment was tolerated moderately well, with eight patients not requiring any analgesia; three treated with opioids intravenously during the procedure, due to burning sensations; and one undergoing separation of adhesions under general anesthesia. Minimal local toxicity included vulvar erythema but no necrosis, sloughing, or scarring. No generalized cutaneous photosensitivity was present. Six to 8 weeks after photodynamic therapy, pruritus significantly improved in ten of the 12 women. A prolonged effect of photodynamic therapy was reported, with a mean of 6.1 months. CONCLUSION: Photodynamic therapy after topical application of 5-aminolevulinic acid produced statistically significant relief of symptoms of vulvar lichen sclerosus for an average of 6.1 months with minimal side effects.

Adult↗
PubMed1999

A hierarchical clustering method for analyzing functional MR images.

We introduce a novel method for detecting anatomic and functional structures in fMRI. The main idea is to divide the data hierarchically into smaller groups using k-means clustering. The separation is halted if the clusters contain no further structure that is verified by several independent tests. The resulting cluster centers are then used for computing the final results in one step. The procedure is flexible, fast to compute, and the numbers of clusters in the data are obtained in a data-driven manner. Applying the algorithm to synthetic fMRI data yields perfect separation of "anatomic," i.e., time-invariant, and "functional," i.e., time-varying, information for a standard off-on paradigm and a typical functional contrast-to-noise ratio of two and higher. In addition, an EPI-fMRI data set of the human motor cortex was analyzed to demonstrate the performance of this novel approach in vivo.

Algorithms↗
PubMed1999

Assessment of cluster homogeneity in fMRI data using Kendall's coefficient of concordance.

In fMRI both model-led and exploratory data-driven methods are used to identify groups of voxels according to their correlation either with an external reference or with some similarity measure. Here we present a technique to assess intragroup homogeneity using Kendall's coefficient of concordance W once groups have been identified. We show that the time-courses belonging to the group may be ranked according to their contribution to the overall concordance and describe an algorithm for group purification. We suggest the use of W as a cluster validation index in exploratory data analysis approaches, such as fuzzy or hard clustering, principal component analysis, independent component analysis and Kohonen maps.

Algorithms↗
PubMed1999

Photodynamic cystoscopy for detection of bladder tumors.

The use of a photodynamic fluorescence marker for diagnosis of tumors is an intriguing concept to improve thoroughness of surgical tumor resection. Complete surgical resection of multifocal bladder tumors and flat lesions as carcinoma in situ is known to be difficult, and thus a source of recurrencies. We report on the recent experience with the intravesical application of the photosensitizer prodrug 5-aminolevulinic acid (5-ALA), which is a nontoxic physiological heme substrate. Initial results from fluorescence diagnosis using krypton laser light and recent results with a modified incoherent light source constantly showed a 25% increase in urothelial tumor detection compared with white light endoscopy. Because of the high sensitivity, the number of biopsies could be decreased constantly compared with routine random biopsies taken under white light endoscopy. The results show about 25% to 30% of cases with fluorescent lesions, which are histologically benign. 5-ALA is a promising tool for diagnosis of bladder cancer. The outcome of the initial study of 5-ALA in urology in Germany is positive and is continued by prospective multicenter clinical studies to prove the hypothesis of reduction of tumor recurrence with this method. 5-ALA-based fluorescence endoscopy is strongly recommended for further clinical testing.

Adenocarcinoma, Papillary↗