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Biomedical subjects

R Baumgartner

Publications and source records attributed to R Baumgartner.

At least 73 records · Page 4Linked to original sources
PubMed1999

Ho:YAG laser treatment of hyperplastic inferior nasal turbinates.

OBJECTIVES: Although preliminary studies about the successful use of the Ho:YAG laser in nasal turbinate surgery have been reported, no clinical study has been performed on this procedure. The aim of this prospective clinical study was to assess the long-term effect of Ho:YAG laser in the treatment of hyperplastic inferior nasal turbinates. METHODS: Eighty-five patients with nasal obstruction who did not respond to conservative medical treatment were treated with a pulsed Ho:YAG laser (wavelength of =2080 nm). Fifty-two of these patients were included in this clinical study and were followed for 1 year. RESULTS: Within the first 2 weeks, nasal obstruction was correlated to the extent of nasal crusting. Six months after laser treatment, the mucociliary function test showed no variation compared with the preoperative measurements. One year after laser treatment 77% of the patients demonstrated improved nasal airflow on rhinomanometry and questionnaire. CONCLUSIONS: Ho:YAG-laser treatment of hyperplastic turbinates can be performed as outpatient surgery under local anesthesia and offers controllable ablation of soft tissue in a short operation time with satisfactory results and excellent patient acceptance.

Feasibility Studies↗
PubMed1999

Transurethral resection and surveillance of bladder cancer supported by 5-aminolevulinic acid-induced fluorescence endoscopy.

PURPOSE: We determined whether neoplastic disease, which was missed under white light can be found during transurethral resection of bladder cancer by 5-aminolevulinic acid-induced porphyrin fluorescence. MATERIALS AND METHODS: 5-Aminolevulinic acid-induced fluorescence endoscopy was carried out in 328 cases. A 3% 5-aminolevulinic acid solution was instilled intravesically in a mean time of 2.8 h before endoscopy. The fluorescence was excited by a special incoherent light source which provided blue light in addition to white light. RESULTS: In 82 (25%) cases additional neoplastic lesions were found only because of their red porphyrin fluorescence which was induced by 5-aminolevulinic acid. 31% of these neoplastic foci which were found in normal and nonspecific inflamed mucosa had a poorly differentiated histology. CONCLUSIONS: 5-Aminolevulinic acid facilitates detection of neoplastic disease during transurethral resection of bladder cancer and increases the accuracy of diagnosis.

Adenocarcinoma, Papillary↗
PubMed1999

5-Aminolevulinic acid-induced fluorescence endoscopy for the detection of lower urinary tract tumors.

The use of a photodynamic fluorescence marker for diagnosis of tumors is an intriguing concept to improve the thoroughness of surgical tumor resection. Complete surgical resection of multifocal bladder tumors and flat lesions such as carcinoma in situ is known to be difficult, and thus a source of recurrences. 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 in comparison to white light endoscopy. Due to the high sensitivity, the number of biopsies could be decreased constantly in comparison to routine random biopsies taken under white light endoscopy. The results show about 25-30% of cases with fluorescent lesions which are histologically benign. 5-ALA is a promising tool for the diagnosis of bladder cancer. The outcome of the admission study for 5-ALA in urology in Germany is positive, and is being 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.

Administration, Intravesical↗
PubMed1999

[Surgical management of neuropathy and osteoarthropathy of the diabetic food].

Along with angiopathy, neuropathy and osteoarthropathy are the most important effects of diabetes mellitus with regard to the foot. Because diagnosis in cases of these two consequences are very frequently wrong and too late, the diagnostic procedure and differential diagnosis will be discussed first. The goal of surgical and conservative treatment is a functioning foot and not amputation and provision of a prosthesis. The five types of osteoarthropathy together with the operative procedure for each are introduced: at the forefoot, resection of from one to all metatarsal radii whilst sparing the toes; at the metatarsus, the removal of projecting fragments; at the dorsal foot, resectioning arthroplasty. The operative procedures usual in traumatology cannot simply be transferred to osteoarthropathy. Arthrodeses and spongiosa grafting are doomed to failure in the neuropathic area, or at least carry the onus of a much longer period of convalescence. Resectioning arthroplasty for constructing a stiff pseudarthrosis is an alternative. The results are, however, only lasting if perfect orthopedic care and regular care and checking of the feet are guaranteed thereafter.

Arthropathy, Neurogenic↗
PubMed1998

Structure of human cyclin-dependent kinase inhibitor p19INK4d: comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16INK4a.

BACKGROUND: The four members of the INK4 gene family (p16(INK4a), p15(INK4b), p18(INK4c) and p19(INK4d)) inhibit the closely related cyclin-dependent kinases CDK4 and CDK6 as part of the regulation of the G1-->S transition in the cell-division cycle. Loss of INK4 gene product function, particularly that of p16(INK4a), is found in 10-60% of human tumors, suggesting that broadly applicable anticancer therapies might be based on restoration of p16(INK4a) CDK inhibitory function. Although much less frequent, defects of p19(INK4d) have also been associated with human cancer (osteosarcomas). The protein structures of some INK4 family members, determined by nuclear magnetic resonance (NMR) spectroscopy and X-ray techniques, have begun to clarify the functional role of p16(INK4a) and the dysfunction introduced by the mutations associated with human tumors. RESULTS: The crystal structure of human p19(INK4d) has been determined at 1.8 A resolution using multiple isomorphous replacement methods. The fold of p19(INK4d) produces an oblong molecule comprising five approximately 32-residue ankyrin-like repeats. The architecture of the protein demonstrates the high structural similarity within the INK4 family. Comparisons to other ankyrin-repeat-containing proteins (GABPbeta, 53BP2 and myotrophin) show similar structures with comparable hydrogen-bonding patterns and hydrophobic interactions. Such comparisons highlight the splayed beta-loop geometry that is specific to INK4 inhibitors. This geometry is the result of a modified ankyrin structure in the second repeat. CONCLUSIONS: Among the INK4 inhibitors, the highest amino acid sequence conservation is found in the helical stacks; this conservation creates a conserved beta-loop geometry specific to INK4 inhibitors. Therefore, in addition to models which predict that the conserved helix alpha6 is responsible for CDK inhibition, a binding mode whereby the loops of INK4 proteins bind to the CDKs should also be considered. A similar loop-based interaction is seen in the complex formed between the ankyrin-repeat-containing protein GABPbeta and_GABPalpha. This mode of binding would be consistent with the observation that p16(INK4a) is sensitive to deleterious mutations found throughout this tumor suppressor protein; these mutations probably destabilize the three-dimensional structure.

Amino Acid Sequence↗
PubMed1998

Backbone dynamics of the CDK inhibitor p19(INK4d) studied by 15N NMR relaxation experiments at two field strengths.

The four members of the INK4 gene family, p16(INK4a), p15(INK4b), p18(INK4c) and p19(INK4d), are known to bind to and inhibit the closely related cyclin-dependent kinases CDK4 and CDK6 as part of the regulation of the G1/S transition in the cell division cycle. Loss of INK4 gene product function, and particularly that of p16(INK4a), is found in human cancer. 15N NMR relaxation rates of p19(INK4d) were analyzed using the reduced spectral density mapping method. Most of the backbone of p19(INK4d) exists in a well-defined structure of limited conformational flexibility on the nanosecond to picosecond time-scales. Introducing appropriate scaling to account for the effects of anisotropy, a considerable amount of exchange broadening was found for several residues throughout the sequence, especially residues in the second ankyrin repeat and in the beginnings and ends of loops connecting ankyrin repeats. A possible mode of binding between p19(INK4d) and CDK4 and CDK6 could therefore involve the loop segments of p19(INK4d). The average overall correlation time taumeff was determined to be 13.6 ns, reflecting the tendency of p19(INK4d) to aggregate.

Anisotropy↗
PubMed1998

Early clinical experience with 5-aminolevulinic acid for the photodynamic therapy of upper tract urothelial tumors.

PURPOSE: Photodynamic therapy is effective in the treatment of superficial urothelial cancer of the bladder. We report our experience with photodynamic therapy for the treatment of upper urinary tract transitional cell carcinoma. MATERIALS AND METHODS: Photodynamic therapy after oral administration of 5-aminolevulinic acid was performed in 4 patients with widespread superficial papillary tumors of the upper urinary tract. RESULTS: Complete remission occurred in 2 patients who remained free of local recurrence at 7 and 17 months of followup. In the other 2 patients residual tiny papillary tumors were found in the distal ureter after photodynamic therapy. These tumors were coagulated with neodymium:YAG laser irradiation. Both patients are disease-free at 24-month followup. CONCLUSIONS: Photodynamic therapy with 5-aminolevulinic acid is a minimally invasive approach for organ preserving treatment of multifocal superficial transitional cell carcinoma of the upper urinary tract.

Aged↗
PubMed1998

Quantification in functional magnetic resonance imaging: fuzzy clustering vs. correlation analysis.

The potential of functional MRI (fMRI) data analysis using the paradigm independent fuzzy cluster analysis (FCA) applied in the time domain compared to frequently used paradigm based correlation analysis (CA) was studied with simulated and in vivo fMRI data. The performance of FCA and CA was investigated in a typical contrast-to-noise range for fMRI, ranging from 1.33 to 3.33. Using simulated fMRI data the methods were quantitatively compared in terms of generation of true positives, false positives, and the corresponding signal enhancement. Even without prior knowledge about the stimulation paradigm and the actual hemodynamic response function the performance of FCA was comparable to that of CA where extensive prior knowledge has to be added. Furthermore, discrimination of nonanticipated hemodynamic responses by FCA, such as different levels of activation and delayed response, are demonstrated in simulated and in vivo fMRI data. We demonstrate that using CA one cannot differentiate between these responses at least without extensive prior knowledge, i.e., FCA yields a more particular description of fMRI data. This may be worthwhile for analysis and optimization of data quality in fMRI as well as in the final data analysis.

Adult↗
PubMed1998

Prevalence of proteinuria/microalbuminuria in an elderly urban, biethnic community.

INTRODUCTION: The purpose of this study was to compare the prevalences of urinary abnormalities, notably proteinuria and microalbuminuria, in a randomly selected, biethnic population of Hispanic and nonHispanic white males and females and to determine the effects of diabetes, hypertension, and coronary heart disease on these prevalence rates. METHODS: A survey of health and health related issues was conducted on 883 volunteers, mean age 74.1 years, selected randomly from the Medicare rolls of Bernallilo County (Albuquerque), New Mexico. The sample consisted of nearly equal numbers of Hispanic and nonHispanic white males and females. A dipstick urinalysis and test for microalbuminuria was performed on a clean void, untimed urine sample as a part of a 4-hour interview/examination. RESULTS: Of the 696 participants with complete databases, 10.5% had 1+ or greater proteinuria (30 mg/dL or more) by convential urinalysis dipstick and 19.8% had microalbuminuria (50 mg/L or more) by Micral Chemstrip methodology. Participants with diabetes mellitus (Odds Ratio (OR) 2.54, Confidence Interval (CI) 1.71-3.76, p < 0.001), and/or hypertension (OR 2.09, 95% CI 1.46-3.01, p < 0.001) were more likely to have microalbuminuria than participants without either of these conditions. After adjusting for the presence of diabetes and hypertension, there was a trend toward an increased prevalence of coronary heart disease (OR 1.23, 95% CI 0.84-1.81 p = 0.28) in those with microalbuminuria, but this did not reach levels of statistical significance. CONCLUSIONS: Hispanics, even after adjusting for a higher prevalence of diabetes, and for small differences in prevalences of hypertension and coronary heart disease, had more microalbuminuria than nonHispanic whites, and males had more microalbuminuria than females.

Aged↗
PubMed1998

Fluorescence endoscopy of gastrointestinal diseases: basic principles, techniques, and clinical experience.

Visual detection of tumors, especially during the early stages, is expected to be improved considerably by examining the fluorescence either of tumor-selective exogenous dyes such as protoporphyrin IX, induced by 5-aminolevulinic acid, or by analyzing the autofluorescent properties of healthy and neoplastic tissue. The present paper describes technical devices using light sources for fluorescence excitation, and sensitive detection systems such as intensified cameras and optical multichannel analyzers used for fiber-assisted point measurements. In the discussion of these systems, special consideration is given to their commercial availability and potential for endoscopic applications in the gastrointestinal tract. In this clinical discipline, the major interest lies in the ability to locate malignancies in the esophagus and colon. In recent years, there has been increasing clinical experience in this area, particularly in detecting adenocarcinoma in Barrett's esophagus and malignant alterations in the colon, such as in ulcerative colitis and polyps. Although several research groups have reported sensitivities and specificities for fluorescence gastroscopy of more than 80%, the potential benefits of the technique to patients need to be evaluated in further clinical studies.

Clinical Trials as Topic↗
PubMed1998

Local intra-arterial thrombolysis in acute ischemic stroke.

BACKGROUND AND PURPOSE: We performed a retrospective analysis of the prognostic factors in patients treated with local intra-arterial thrombolysis (LIT). The purpose of this study was to evaluate the safety and efficacy of LIT using urokinase in patients with acute ischemic stroke of the anterior or posterior circulation and to determine the influence of clinical and radiological parameters on outcome. METHODS: Forty-three patients were treated with LIT using urokinase (median dose, 0.75x10(6) IU). The median National Institutes of Health Stroke Scale (NIHSS) score at hospital admission was 18 (range, 9 to 36). Nine patients had occlusions of the internal carotid artery (ICA), 23 of the middle cerebral artery (MCA), 1 of the anterior cerebral artery, and 10 of the basilar artery (BA). Outcome was assessed after 3 months and classified as good for Rankin Scale (RS) scores of 0 to 3 and poor for RS scores of 4 or 5 and death. RESULTS: Nine patients (21%) recovered to RS scores 0 or 1, 17 (40%) to scores of 2 or 3, and 7 (16%) to scores of 4 or 5. Ten patients (23%) died. Outcome was good in 17 patients (80%) with MCA occlusions, in 3 patients (33%) with ICA, and in 5 patients (50%) with BA occlusions. Good outcome was associated with an initial NIHSS score of <20 (P<0.001), improvement by 4 or more points on NIHSS score within 24 hours (P=0.001), and vessel recanalization (P=0.02). Recanalization was more likely if LIT was started within 4 hours (P=0.01). Symptomatic cerebral hemorrhage occurred in 2 patients (4.7%). CONCLUSIONS: LIT was most efficacious in patients with MCA and BA occlusions when the initial NIHSS score was less than 20 and when treated within 4 hours. It is of limited value in patients with distal ICA occlusions.

Acute Disease↗
PubMed1997

NMR structural characterization of the CDK inhibitor p19INK4d.

p19INK4d is a 165 amino acid protein that belongs to the INK4 family of CDK4 and CDK6 inhibitors. Assignments of 1H, 15N and 13C resonances have enabled the determination of the secondary structure of the protein which is largely alpha-helical (residues 14-18, 21-29, 54-62, 77-83, 87-95, 110-116, 120-128, 142-148 and 152-160). The protein comprises five 32-amino acid ankyrin-like repeats; each ankyrin repeat contains a helix-beta-turn-helix core. The exception is the second ankyrin repeat, which lacks the first helix. All beta-turns have a central glycine residue flanked by two residues in beta-conformations. There is also a high conservation of Ala at position 8 in the first helix and Leu-Leu(Val) at positions 17-18 of the second helix in all ankyrin repeats of p19. The location of the helix-turn-helix segments found in p19 should be general for all other members of the INK4 family, including, for example, a homologous tumor suppressor p16INK4a. 1H-15N heteronuclear steady-state NOE measurements on p19 indicate that most of the backbone of p19INK4d exists in a well defined structure of limited conformational flexibility on the nano- to picosecond time scale.

Amino Acid Sequence↗
PubMed1997

Arg538 to Cys mutation in a CpG dinucleotide of the human biotinidase gene is the second most common cause of profound biotinidase deficiency in symptomatic children.

Biotinidase deficiency is an autosomal recessively inherited disorder in the recycling of the vitamin biotin. The most common mutation that causes profound biotinidase deficiency in symptomatic individuals is a deletion/insertion (G98:d7i3) that occurs in exon B of the biotinidase gene. We now report the second most common mutation, a C-to-T substitution (position 1612) in a CpG dinucleotide in exon D of the biotinidase gene. This mutation results in the substitution of a cysteine for arginine538 (designated R538C) and was found in 10 of 30 symptomatic children with profound biotinidase deficiency, 5 of whom also have the G98:d7i3 mutation. This mutation was not found in DNA samples from 32 individuals with normal biotinidase activity, but was found in one individual with enzyme activity in the heterozygous range. This mutation was not detected in 371 randomly selected, normal individuals using allele-specific oligonucleotide hybridization analysis. Aberrant biotinidase protein was not detectable in extracts of fibroblasts from a child who is homozygous for the R538C mutation, but was present in less than normal concentration in identical extracts treated with beta-mercaptoethanol. Because there is no detectable biotinidase protein in sera of children who are homozygous for the R538C mutation and in combination with the deletion/insertion mutation, the R538C mutation likely results in inappropriate intra- or intermolecular disulfide bond formation, more rapid degradation of the aberrant enzyme, and failure to secrete the residual aberrant enzyme from the cells into blood.

Acyltransferases↗
PubMed1997

In vivo fluorescence kinetics of porphyrins following intravesical instillation of 5-aminolaevulinic acid in normal and tumour-bearing rat bladders.

The fluorescence kinetics of protoporphyrin IX (PPIX) following intravesical instillation of 5-aminolaevulinic acid (5-ALA) have been studied in vivo in a rat bladder tumour model. 5-ALA dissolved in NaHCO3 was intravesically instilled for 60 min in tumour-bearing and normal bladders of Wistar rats. The fluorescence was excited with the violet lines of a Kr(+)-laser and recorded in vivo by means of a fibre coupled optical multichannel analyser. The fluorescence emission bands of PPIX at lambda = 636 nm and lambda = 708 nm were detected in normal and tumorous urothelium after only 30 min. The maximum fluorescence intensity was obtained in tumorous and normal urothelium 3-4 h after instillation. The ratio of the fluorescence intensity in tumorous to normal urothelium decreased continuously from four to about two during the time range of 6 h. PPIX fluorescence following 5-ALA instillation could also be observed in kidney and liver. Fluorescence from further porphyrin species with emission bands at lambda = 617 nm and lambda = 682 nm was detected in the bladder, indicating an efflux of hydrophilic porphyrins from the hepatic pathway.

Administration, Intravesical↗
PubMed1997

H-dependent formation of 5-aminolaevulinic acid-induced protoporphyrin IX in fibrosarcoma cells.

pH-Dependent variations in the fluorescence intensity of 5-aminolaevulinic acid-induced 5-aminolaevulinic acid protoporphyrin IX (PP IX) were compared with the cell viability following light irradiation. The fluorescence intensity was determined by flow cytometry and the cell activity was investigated by a colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay 24 h after photodynamic treatment. The results obtained by fluorescence measurements clearly showed that pH values of the incubation medium containing (5-ALA) below and above pH 7.4 led to a significant decrease in the fluorescence intensity. The viability of cells incubated with 0.6 mM 5-ALA in a medium at pH 6.0 was unaffected on exposure to light at lambda = 635 nm up to 15 J cm-2. However, cells incubated at pH 7.4 (with the other treatment parameters the same) were nearly completely destroyed. In addition, depletion of intracellular PPIX was faster in physiological medium than in acid medium.

Aminolevulinic Acid↗
PubMed1997

Pharmacokinetics of 5-aminolevulinic acid-induced protoporphyrin IX in skin and blood.

The fluorescence and photosensitivity of endogenously synthesized protoporphyrin IX (PPIX) is increasingly used for the diagnosis and treatment of malignant and certain non-malignant diseases. A selective accumulation of PPIX can be induced by application of 5-aminolevulinic acid (5-ALA), which is a precursor of PPIX in the cellular biosynthetic pathway of heme. The purpose of this study was to monitor the in vivo accumulation of PPIX in different locations of the skin after oral ingestion and to determine the pharmacokinetics of 5-ALA and PPIX in human blood plasma for various routes of application. At the same time we wanted to achieve an optimal treatment scheme but also study possible side-effects of 5-ALA administration. After oral application of 5-ALA in a concentration of 40 mg kg-1 body weight, the fluorescence intensities of PPIX in the skin showed maxima between 6.5 and 9.8 h depending on the location and decreased to values lower than 5% related to the maximum after a mean time of about 40 h. The measured absolute intensities of PPIX fluorescence varied strongly between different patients and different locations on one patient. In the plasma of blood samples, PPIX could be detected via its fluorescence for all studied routes of application with the exception of the ointment, where PPIX levels were below the detection limit of 1 microgram l-1. The highest mean concentration of 742 micrograms l-1 PPIX in the plasma was measured 6.7 h after oral application. For inhalation of 5-ALA, a mean maximum concentration of 12 micrograms l-1 could be detected 4.1 h after application, for intravesical instillation, the mean maximum concentration was found to be 1 microgram l-1 2.9 h after application. The kinetics of 5-ALA in the plasma peaked much earlier with a maximum concentration of 32 mg l-1 about 30 min. after oral administration. The 5-ALA levels did not exceed normal reference values after topical application. The results of our experiments suggest that for a systemic application of 5-ALA side-effects in sensitive patients cannot be excluded.

Aged↗
PubMed1997

[Special technics for angioplasty of the brachiocephalic vessels].

PURPOSE: Description of special techniques for retrograde angioplasty of cerebral arteries with protection of the brain. MATERIAL AND METHOD: During the last 3 years, 51 dilatations of cerebral vessels were carried out in 45 patients; in 8, special techniques were required. In cases with particular operative risks, angioplasty of cerebral vessels can be performed using various techniques (double catheter [8 cases], retrograde PTA [8 cases], kissing balloon technique [3 cases]). RESULTS: All stenoses were successfully dilated, using a local anaesthetic. One patient with a double stenosis of the common carotid artery developed severe headache and visual disturbances in the ipsilateral eye following dilatation of a tight stenosis with total remission of all symptoms within 24 hours. CONCLUSION: Stenoses of cerebral arteries where surgery would be difficult and associated with a high risk can be dilated by retrograde PTA using a double catheter technique with a low complication rate.

Aged↗