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Biomedical subjects

Gerhard Friedrich

Publications and source records attributed to Gerhard Friedrich.

11 recordsLinked to original sources

Laryngo-tracheal profile: a new method for assessing laryngo-tracheal stenoses.

We present the clinical application of a new method for objective assessment of both grade and length of laryngo-tracheal stenoses (LTS) on a CT-based skeletonization algorithm, called laryngo-tracheal profile (LTP). Extraction of the laryngo-tracheal tract (LTT)-medial axis was performed after S-CT scanning. Orthogonal to the medial axis, the LTT cross-profile was computed, and the length and degree of LTS were presented as line charts. Clinical application of this newly developed method is demonstrated on three patients who had to undergo preoperative assessment before surgical treatment of tracheal stenoses. LTP provides an objective method of assessment of both the length and degree of tracheal stenoses in precise correlation to defined anatomical landmarks. This method provides important additive information for preoperative evaluation as well as for monitoring of therapeutical success. Current methods used so far are able to evaluate the severity of LTS, but do not provide exact quantitative assessment of complex LTS. Especially in CT-scans of strong curved passages, where an overestimation of the cross-sectional area results by an oblique cut of the tubular structure, LTP may overcome this problem by a simple post processing skeletonization algorithm.

Adult↗

Enzyme induction in cryopreserved human hepatocyte cultures.

Freshly isolated human hepatocytes are considered as the gold standard for in vitro testing of drug candidates. Meanwhile also cryopreserved human hepatocyte suspensions are available. However, a drawback of these cells is the incalculability of attachment to the culture dish. Therefore, we established a technique freezing hepatocytes cultured on a collagen gel. After thawing damaged cells were removed to a certain extent by gentle washing with culture medium prior to adding an upper gel layer. The morphology of the resulting hepatocyte cultures could not be distinguished from that of non-frozen cells. However, basal activities of cytochrome P450 isoforms decreased in cryopreserved compared to non-frozen hepatocytes, as evidenced by analysis of testosterone hydroxylation (OHT) in positions 6beta, 16alpha, 2beta and 6alpha. Nevertheless, enzyme induction factors caused by 24 h incubation with 50 microM rifampicin were similar in cryopreserved and non-frozen hepatocytes. In cryopreserved hepatocytes rifampicin caused an increase in mean values of 6beta-OHT formation from 57.2 to 157.7 pmol/well/min (2.8-fold), compared to an increase from 115.8 to 269.1 pmol/well/min (2.3-fold) in non-frozen cells. Similarly, 16alpha- and 2beta-OHT showed induction factors of 2.4- and 2.3-fold in cryopreserved compared to 1.6- and 2.4-fold in non-frozen hepatocytes, respectively. In conclusion, human hepatocytes cryopreserved on collagen gels show a clear induction of CYP3A4 by rifampicin, although the basal activities are reduced compared to non-frozen cells.

Aged↗

Determination of dihydroergocryptine in human plasma and urine samples using on-line sample extraction-column-switching reversed-phase liquid chromatography-mass spectrometry.

A rapid and sensitive assay for the determination of dihydroergocryptine (DHEC) in human plasma and urine samples with dihydroergotamine (DHET) as the internal standard was developed. The procedure employs on-line sample preparation using an extraction pre-column and an octadecylsilylsilica (ODS) analytical column. After centrifugation human plasma or urine were injected onto the pre-column, concentrated and extracted, back-flushed onto the analytical column and eluted with a binary methanol--aqueous formic acid gradient. Either determination of DHEC as well of its mono- and dihydroxy-metabolites was performed by measurement of the signal responses from MS detection in the selected reaction monitoring (SRM) mode using the transition of the respective parent ions to the common daughter ion at m/z=270.2 amu. The limit of quantitation (LOQ) for determinations of DHEC in both plasma and urine were 25 pg/ml for injected sample volumes of 400 microl. Proportionality of signal responses versus concentration was accomplished within the range of 25-1000 pg/ml. Recovery of target analyte from plasma was 99%. Mean values of the coefficients of variation (CV) for the target analyte in plasma ranged from 1.7 to 13.8% (within-day) and 5.0 to 9.1% (between-day) and accuracy from 91.7 to 102.6% for the within-day and from 95.8 to 98.8% for the between-day measurements. The corresponding values for determinations in urine were 1.7-14.5% (within-day) and 5.3-11.8% (between-day) for CV and 95.8-110.7% (within-day) and 100.1-104.6% (between-day) for accuracy.

Chromatography, High Pressure Liquid↗

Determination of testosterone metabolites in human hepatocytes. I. Development of an on-line sample preparation liquid chromatography technique and mass spectroscopic detection of 6beta-hydroxytestosterone.

A rapid and sensitive RP-HPLC assay for determination of 6beta-hydroxytestosterone in human hepatocytes with corticosterone as the internal standard is described. The procedure employs on-line sample enrichment using a BioTrap 500 MS (20x4 mm I.D.) extraction pre-column and subsequent gradient separation on a Prontosil 60-5 C(18)-H (250x2 mm I.D., 5 micrometer particle size) analytical column in the back-flush mode using a ternary eluent system composed of methanol, tetrahydrofuran and water. Signal monitoring was done by measurement of the responses from liquid chromatography coupled to mass spectroscopy (LC-MS/MS) using an atmospheric pressure chemical ionization (APCI) source conducted in the selected reaction monitoring (SRM) mode. Mean recoveries of 6beta-hydroxytestosterone from an estimate of the biological matrix, i.e., Dulbecco's modified Eagle medium "High Glucose", ranged from 101.8-104.4% for samples containing the target analyte at the 250, 500 and 1000 ng/ml level. The limit of quantitation (LOQ) was 20 ng/ml at an injection volume of 100 microliter determined in the same matrix. Linearity of signal responses versus concentration for all three analytes was accomplished in the range of 100-4000 ng/ml. Mean values of the coefficients of variation (C.V.) for the target analyte obtained for the concentrations 250, 500 and 1000 ng/ml at 5 different days in quintuplicate ranged from 1.5-7.7% (within-day) and 4.8-7.3% (between-day). The corresponding values for the accuracy ranged from 87.7-106.1% for the within-day and from 98.8-102.5% for the between-day measurements. The target analyte was sufficiently stable at both storage and sample preparation conditions because no substantial deviations between analyte concentrations measured before and after subsequently performed freeze and thaw cycles were observed.

Chromatography, High Pressure Liquid↗

Determination of lonazolac and its hydroxy and O-sulfated metabolites by on-line sample preparation liquid chromatography with fluorescence detection.

A reliable method, which can be used for the determination of lonazolac and its hydroxylated and O-sulfated metabolites in cell culture media with methyllonazolac as the internal standard is described. The procedure employs on-line sample enrichment using a BioTrap 500 MS (20 x 4 mm I.D.) extraction pre-column and subsequent gradient separation on an Xterra MS C18-HT (100 x 3 mm I.D., 3.5 microm particles) analytical column in the back-flush mode. Signal monitoring was done by measurement of fluorescence responses at 273 nm for excitation and 385 nm for emission. Structural identity of analyte peaks was confirmed by liquid chromatography coupled to mass spectroscopy (LC-MS-MS) using an electrospray ionization (ESI) source in the selected reaction monitoring (SRM) mode. Mean recoveries of lonazolac, hydroxylonazolac and lonazolac sulfate, respectively, from the biological matrix were 104.2 +/- 3.5, 96.7 +/- 2.2, and 100.9 +/- 3.5%. The limit of detection (LOD) for the three compounds was about 5 ng/ml using a total sample volume of only 50 microl. Linearity of signal responses versus concentration for all three analytes was accomplished in the range 10-600 ng/ml. The mean values of the coefficients of variation (CV) for quality control samples measured in duplicate at three different days at the 10, 40, 100, and 400 ng/ml level were 4.46 +/- 1.15, 3.94 +/- 2.13 and 4.79 +/- 2.07% for lonazolac, hydroxylonazolac and lonazolac sulfate. The target analytes were sufficiently stable at both storage and sample preparation conditions because no substantial deviations between analyte concentrations measured before and after subsequently performed freeze and thaw cycles were observed.

Anti-Inflammatory Agents, Non-Steroidal↗

Nasalance changes after functional endoscopic sinus surgery.

Forty adult patients diagnosed with chronic rhinosinusitis who underwent functional endoscopic sinus surgery (FESS), were analyzed with respect to postoperative resonatory voice changes. For evaluation the patients were asked about their subjective impression of voice changes using a questionnaire. An objective assessment was performed by determining the so-called nasalance using the Nasometer (Kay Elemetrics), preoperatively, on the immediate postoperative follow-up (2 days after surgery), and approximately 1 month after surgery. The mean nasalance values increased significantly one month after FESS whereas the immediate postoperative control (2 days after surgery) showed a decrease of nasalance. Although FESS is a minimally invasive procedure, it can change the acoustic characteristics of the vocal tract in the long term and produce a significant increase in nasality. The authors strongly recommend that clinicians inform all patients, in particular voice professionals, about the possible effects of endonasal sinus surgery on voice quality.

Adolescent↗

Short-term therapeutic trial of proton pump inhibitors in suspected extraesophageal reflux.

Pharyngoesophageal gastric acid reflux is thought to initiate chronic posterior laryngitis. The gold standard for measuring gastric reflux is dual-channel 24-hour pH monitoring. This is a time-consuming, inconvenient, expensive method that is not available in all areas. New therapeutic regimes that make use of proton pump inhibitors (PPIs) have proven to be therapeutically efficient for control of acid reflux. Twenty-four consecutive patients with chronic voice disorders and signs of posterior laryngitis were selected for therapy. Twenty-four hour pH monitoring was performed independently before the therapy. The trial therapy consisted of all patients receiving pantoprazole, 40 mg once daily for 6 weeks. Immediately following the therapy a statistically significant (p < 0.05) improvement was observed in all patients. This improvement was analyzed retrospectively by comparison with the results of 24-hour pH monitoring. In 71% of the patients the 24-hour pH-monitoring gave a positive result showing a high number of patients with extraesophageal reflux in our study group. Patients with positive results of pH-monitoring responded in a statistically significant manner (p < 0.05) to the pantoprazole therapy, whereas those patients without detected reflux did not. A 3-month follow-up of the patients with a positive result of the pH-monitoring confirmed the improvement. No patients reported adverse effects. A 6-week treatment with pantoprazole can be clinically justified. It helps to save time and reduce costs, allows for selection of reflux-negative patients for alternative therapy, and may prevent inadequate treatment of patients with false-negative pH monitoring. Twenty-four hour pH monitoring is still recommended for patients unresponsive to this trial therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Spiral-CT-based assessment of tracheal stenoses using 3-D-skeletonization.

PURPOSE: Demonstration of a technique for three-dimensional (3-D) assessment of tracheal-stenoses, regarding site, length and degree, based on spiral computed tomography (S-CT). PATIENTS AND METHODS: S-CT scanning and automated segmentation of the laryngo-tracheal tract (LTT) was followed by the extraction of the LTT medial axis using a skeletonization algorithm. Orthogonal to the medial axis the LTT 3-D cross-sectional profile was computed and presented as line charts, where degree and length was obtained. Values for both parameters were compared between 36 patients and 18 normal controls separately. Accuracy and precision was derived from 17 phantom studies. RESULTS: Average degree and length of tracheal stenoses was found to be 60.5% and 4.32 cm in patients compared with minor caliber changes of 8.8% and 2.31 cm in normal controls (p << 0.0001). For the phantoms an excellent correlation between the true and computed 3-D cross-sectional profile was found (p << 0.005) and an accuracy for length and degree measurements of 2.14 mm and 2.53% respectively could be determined. The corresponding figures for the precision were found to be 0.92 mm and 2.56%. CONCLUSION: LTT 3-D cross-sectional profiles permit objective, accurate and precise assessment of LTT caliber changes. Minor LTT caliber changes can be observed even in normals and, in case of an otherwise normal S-CT study, can be regarded as artifacts.

Adolescent↗

Surgical voice rehabilitation after laser surgery for glottic carcinoma.

Transoral laser surgery today is the mainstay of treatment for T1 and T2 glottic carcinoma. The vocal ability remains sufficient in the majority of patients. However, in some cases, a significant glottic gap may persist, leading to poor voice quality. We report a special technique of medialization thyroplasty using autologous cartilage specifically adapted for vocal rehabilitation after laser resection. Six patients with a significant glottic gap following laser surgery were treated. For vocal rehabilitation, a special medialization technique was performed. The superior rim of the thyroid cartilage of the resected side was exposed. A 1 x 2-cm piece of cartilage was harvested and reimplanted into a subperichondrial pouch created on the inner side of the thyroid cartilage. When phonation was optimal, this cartilaginous strut was sutured and/or glued in place. In all 6 cases, the vocal function improved significantly. The dysphonia index (0 = normal, 3 = aphonia), which includes objective parameters as well as expert voice ratings and the patient's perception, increased by 1.1 on average (range, 0.4 to 1.6). The results have been lasting. The established medialization techniques are of limited value in a larynx scarred by laser surgery. Injection augmentation is often futile because the tight scar tissue does not lend itself to augmentation. Implantation of nonorganic material may cause problems if revision surgery for tumor recurrence should become necessary or if the implant protrudes into the scarred endolarynx. The technique reported avoids these pitfalls and leads to voice quality improvement comparable to that of established medialization procedures.

Carcinoma, Squamous Cell↗