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Biomedical subjects

M Kunkel

Publications and source records attributed to M Kunkel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Titrimetric determination of Cremophor EL in aqueous solutions and biofluids: part 2: ruggedness of the method with respect to biofluids.

A titration method for Cremophor EL, as a multicomponent mixture commonly used as non-ionic emulgent for manufacturing certain parenteralia, was developed for quantitative routine analysis in biofluids. A coated wire electrode is used as the end-point indicator in potentiometric titrations of Cremophor EL with sodium tetraphenylborate. The method tolerates a broad pH range, addition of alkanols and components of drug formulations and is sufficiently rugged. Reliable results are obtained at 20 degrees C. Disturbing ions from biofluid matrices can be masked or complexed by addition of formaldehyde, ethylenediaminetetraacetic acid and sodium fluoride. Sodium hydroxide is used for the required adjustment of the samples to pH 10. Cremophor EL spiked urine samples can be determined directly, whereas the true value of the emulgent content in the case of Cremophor EL spiked plasma samples is achieved by means of a conventional method.

Alcohols↗
PubMed1999

Continuous wave Doppler ultrasound for evaluation of vasomotor tone of the radial artery.

OBJECTIVE: At present, the sympathetic skin response (SSR) is the only routinely employed technique for evaluating the autonomic function of peripheral nerves. The present study was conducted in order to compare SSR to continuous wave Doppler (CWD) of the radial artery in both healthy control subjects and patients with lower brachial plexus lesions. METHODS: Both methods were performed in 50 healthy volunteers (aged 23 to 70 years; mean age and standard deviation, 39.6+/-14.3 years) and six patients presenting with severe lesions of the lower brachial plexus (aged 22 to 60 years; mean age, 37.6+/-16.0 years). RESULTS: In each control subject, a SSR could be evoked with a mean latency of 1.2+/-0.2 s and a mean amplitude of 2.9+/-1.5 mV. In 45 healthy subjects, CWD revealed both a reduction of systolic, diastolic, and mean peak blood flow velocity after electrical (ES) and acoustic (AS) stimulation as well as after inspiratory cough (IC). The mean latencies to the decrease in flow velocity decrease amounted to 1.8+/-0.7, 2.0+/-0.7, and 1. 4+/-0.4 s, respectively. The resistance (Pourcelot) index increased significantly. CWD failed to show changes of blood flow velocity in five healthy subjects due to high sympathetic tone (no baseline diastolic blood flow) or instability of blood flow caused by respiration. In patients with lower brachial plexus lesions, SSR was diminished and changes in blood flow could not be observed on the affected side. CONCLUSION: CWD sonography allows easy quantitative assessment of arteriolar tone in healthy subjects and patients with autonomic nerve lesions of the limbs.

Acoustic Stimulation↗
PubMed1999

Acoustic airway profiles in unilateral cleft palate patients.

OBJECTIVE: This study investigates the nasal airway in unilateral cleft palate patients by means of a noninvasive, objective diagnostic method that provides topographic information about the airway profile. DESIGN: A consecutive sample of patients was measured. SETTING: Cleft palate rehabilitation center of the University of Mainz, Germany. PATIENTS: Forty-nine subjects were investigated: 34 full-grown patients with complete unilateral cleft lip and palate and 15 controls with subjective normal nasal patency. INTERVENTION: A transnasal series of three acoustic measurements of nasal volume was performed per nostril; measurements were taken both before and after decongestion with 0.3 mg xylometazoline per nostril. Minimum cross-sectional area, nasal volume, and decongestion capacity were calculated for both the cleft side and the contralateral side and for both nasal sides in controls. RESULTS: Pathologic obstructions (<0.4 cm2) were detected on the cleft side in 75% of patients but were detected in only 15% of patients on the contralateral side (p < .001). The valve area of the cleft side (0.32 +/- 0.2 cm2) yielded significantly (p < .001) lower cross-sectional values compared with the contralateral side (0.56 +/- 0.1 cm2). Total nasal volume was determined to be 35% smaller on the cleft side (p < .001). Significantly higher decongestion capacity was verified on the cleft side, thus indicating mucosal hypertrophy. CONCLUSION: Despite a wide range of interindividual variability, we recognized a characteristic "descending W"" airway pattern in cleft palate patients. Acoustic rhinometry seems to be a powerful tool for acquiring topographic information about the individual airway profile. It has proven helpful in visualizing the location and amount of pathologic obstructions, rendering it especially useful for preoperative investigation and quality control in corrective cleft nose surgery.

Acoustics↗
PubMed1999

Parallel syntheses of disulfide inhibitors of the thioredoxin redox system as potential antitumor agents.

We have reported previously that unsymmetrical disulfide inhibitors of the human thioredoxin/thioredoxin reductase redox system (hTrx/TR) possess antitumor activity. We have broadened the search for more potent inhibitors and evaluated a large range of mono- and bis-disulfide compounds, prepared using parallel syntheses. Reaction of isothioisourea-HCI salts (R') or bis-salts (R) with aromatic or aryl thiols (R") in wells of 96-well plates produced >450 derivatives with the structures R"SSR' and R"SSRSSR". The excellent yield and purity of the disulfides provided sufficient material for evaluations of enzyme inhibition and cytotoxicity. Selection criteria based on the IC50 values for hTrx/TR inhibition and for cytotoxicities of the disulfides identified agents for subsequent scale-up syntheses and in vivo evaluations of antitumor activity. These scale-up studies confirmed the original activities of agents synthesized in the plates and validated the parallel synthetic approach. Structure-activity information derived from the hTrx/TR IC50 data allow for a number of generalizations. The most potent inhibitors of the Trx system contained two heteroatoms ortho to the disulfide moiety in an aromatic functionality. The thioalkylating moieties had greatest activity with one branch point alpha to the disulfide. In the absence of branching, more potent inhibition was observed with the electron withdrawing functionalities. Bis-disulfides showed patterns of activity which depended on chain length, with optimum activity observed when the disulfide units were separated by 3.9 A, a similar distance to that separating the thioredoxin active site cysteine residues. From the agents selected for scale-up syntheses, three disulfide compounds were studied for their antitumor activity in vivo against human tumor xenografts in scid mice. One of the analogues discovered through the combinatorial syntheses/screening for Trx inhibition, 1-phenylethyl 2-imidazolyl disulfide, N1 (ProlX agent PX-C5), has demonstrated excellent in vivo activity against the MCF-7 human breast cancer and the HL-60 human leukemia, thus validating this approach for novel drug discovery.

Animals↗
PubMed1998

A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium.

BACKGROUND: Lyme disease is a multisystem inflammatory disease caused by infection with the tick-borne spirochete Borrelia burgdorferi and is the most common vector-borne infection in the United States. We assessed the efficacy of a recombinant vaccine consisting of outer-surface protein A (OspA) without adjuvant in subjects at risk for Lyme disease. METHODS: For this double-blind trial, 10,305 subjects 18 years of age or older were recruited at 14 sites in areas of the United States where Lyme disease was endemic; the subjects were randomly assigned to receive either placebo (5149 subjects) or 30 microg of OspA vaccine (5156 subjects). The first two injections were administered 1 month apart, and 7515 subjects also received a booster dose at 12 months. The subjects were observed for two seasons during which the risk of transmission of Lyme disease was high. The primary end point was the number of new clinically and serologically confirmed cases of Lyme disease. RESULTS: The efficacy of the vaccine was 68 percent in the first year of the study in the entire population and 92 percent in the second year among the 3745 subjects who received the third injection. The vaccine was well tolerated. There was a higher incidence of mild, self-limited local and systemic reactions in the vaccine group, but only during the seven days after vaccination. There was no significant increase in the frequency of arthritis or neurologic events in vaccine recipients. CONCLUSIONS: In this study, OspA vaccine was safe and effective in the prevention of Lyme disease.

Adolescent↗
PubMed1998

Mechanisms of inhibition of the thioredoxin growth factor system by antitumor 2-imidazolyl disulfides.

The interactions of a series of 2-imidazolyl disulfide antitumor compounds with the thioredoxin reductase(TR)/thioredoxin (hTrx) redox system have been studied. Disulfides III-2 (n-butyl 2-mercaptoimidazolyl disulfide) and VI-2 (ethyl 2-mercaptoimidazolyl disulfide) were substrates for reduction by TR with Km values of 43 and 48 microM. Disulfides IV-2 (1-methylpropyl 2-mercaptoimidazolyl disulfide) and DLK-36 (benzyl 2-mercaptoimidazolyl disulfide) were competitive inhibitors of the reduction of hTrx by TR with Ki values of 31 microM. None of the disulfides were substrates for reduction by human glutathione reductase. The disulfides caused reversible thioalkylation of hTrx at the redox catalytic site as shown by the fact that there was no thioalkylation of a mutant hTrx where both the catalytic site Cys32 and Cys35 residues were replaced by Ser. In addition, the disulfides caused a slower irreversible inactivation of hTrx as a substrate for reduction by TR, with half-lives for III-2 of 30 min, for IV-2 of 4 hr, and for IX-2 (t-butyl 2-mercaptoimidazolyl disulfide) of 24 hr. This irreversible inactivation of hTrx occurred at concentrations of the disulfides an order of magnitude below those that inhibited TR, and involved the Cys73 of hTrx, which is outside the conserved redox catalytic site, as shown by the resistance to inactivation of a mutant hTrx where Cys73 was replaced by Ser. Electrophoretic and mass spectral analyses of the products of the reaction between the disulfides and hTrx show that modification of 1-3 Cys residues of the protein occurred in a concentration-dependent fashion. The disulfides inhibited the hTrx-dependent proliferation of MCF-7 breast cancer cells with IC50 values for III-2 and IV-2 of 0.2 and 1.2 microM, respectively. The results show that although the catalytic sites of TR and hTrx are reversibly inhibited by the 2-imidazolyl disulfides, it is the irreversible thioalkylation of Cys73 of hTrx by the disulfides that most probably accounts for the inhibition of thioredoxin-dependent cell growth by the disulfides.

Antineoplastic Agents↗
PubMed1998

Preoperative assessment of airway patency in the planning of corrective cleft nose surgery.

OBJECTIVE: To investigate acoustic assessment of complex structural anomalies in cleft lip and palate associated nasal deformities and its impact on the planning of corrective rhinosurgery. PATIENTS: Twenty-three consecutive patients with unilateral CL(P) during routine consultations, three of them prior to corrective surgery. INTERVENTION: Acoustic measurements of the nasal airway crosssectional area were obtained for both nasal cavities. The size of isthmus area and isthmus location as well as the nasal volume and decongestion capacity in various regions of interest were determined. RESULTS: Obstructions in the area of the nasal valve (< 0.4 cm2) were detected in 85% of the patients on the cleft side, but only 15% on the contralateral side. Severe mucosal hypertrophy was a common finding on the cleft side with a significantly higher capacity of decongestion, especially in the posterior region of the nasal cavity (P < 0.02). A second stenosis located behind the physiological isthmus was found in 16 patients. CONCLUSION: Acoustic rhinometry is a noninvasive, objective method. It measures the degree and the exact location of airway obstructions. Apart from the equipment, the only prerequisite is a cooperative patient. The measurement has direct therapeutic consequences. If the exact cause and location of airway stenosis are known, it is easier to adapt the corrective surgical procedures to suit the individual patient. The decision in favour of additional therapeutic measures can be made on a more rational basis to prevent residual airway problems postoperatively. Preoperative acoustic rhinometry offers valuable information concerning the severity and location of nasal airway obstructions and thus proves to be a helpful tool in the planning of corrective operative measures.

Acoustics↗
PubMed1998

Objective evaluation of velopharyngeal function by acoustic reflection measurements.

OBJECTIVE: To investigate whether acoustic pharyngometry is capable of discriminating velopharyngeal mobility in cleft and non-cleft subjects by determination of epipharyngeal volume changes with active muscle function. DESIGN: Case control study, consecutive sample. SETTING: Cleft palate rehabilitation centre. PATIENTS: Thirty-three consecutive cleft palate patients, among them 10 following pharyngeal flap surgery and 32 controls without velopharyngeal pathology. INTERVENTION: Transnasal acoustic measurements of airway cross-sectional area in the state of relaxed and tensed pharyngeal muscles. Determination of epipharyngeal volume changes by integrating the difference of the airway profile from the choane for a distance of 5 cm (EV0-5). Measurements of defined changes in the epipharynx served as reference. RESULTS: Acoustic pharyngometry is capable of discriminating (P < 0.05: U test, Mann-Whitney) the volume effect of velopharyngeal mobility in CP patients (6.5 cm3) from the control group (8.0 cm3). A 'pharyngeal flap type' and a 'non-pharyngeal flap type' of restriction was observed. The individual effect of velopharyngoplasty on pharyngeal mobility can thus be determined. CONCLUSION: Acoustic pharyngometry is a non-invasive, quantitative investigation technique which seems well suited for the evaluation of velopharyngeal mobility. We expect it to be a helpful tool in objectively monitoring the effect of therapeutic intervention on velopharyngeal mobility, and it may provide a better understanding of the pattern of movement in CP patients.

Acoustics↗
PubMed1998

Spatial-frequency-related efficacy of visual stabilisation of posture.

The present study investigates the efficacy of visual stabilisation of posture for different spatial frequencies of a visual stimulus. Circular sine wave gratings were used to analyse the correlation between perception of motion in depth and stabilisation of fore-aft sway by the mechanism of detecting changes in target size. Body sway was recorded by a force-measuring platform (series A) and, in addition, by simultaneous tracking of infrared markers fixed to the subject's body (series B). Mean velocity and amplitude (RMS) of body sway were calculated in both sagittal (a-p) and lateral (l-r) planes. Sagittal sway was of least magnitude when viewing contrast gratings with lowest thresholds, whereas higher thresholds resulted in increasing sway parameters. As intended by the design of the stimuli, sagittal sway was correlated closer with the stabilising effect exerted by the different stimuli than was lateral sway. Sway velocity was reduced more efficiently, however, with a lower correlation with the psychophysical transfer function, than was RMS sway. Since sway velocity measured by the platform is suggested to depend to a greater extent on dynamic muscle forces generated at each individual body site the results indicate that visual information can be used to reduce and thereby optimise dynamic muscle action (sway velocity) even though static body sway is either not or less reduced. A comparable economisation of sway velocity but not of RMS sway was also seen at the end of posture investigations, indicative of positive training effects.

Adult↗
PubMed1998

[Value of (F18)-2-fluorodeoxyglucose PET scanning in staging mouth cavity carcinoma. Comparative evaluation of PET findings before and after preoperative radiochemotherapy with histological and computerized tomography findings].

OBJECTIVE: The lack of sensitivity and specificity of conventional imaging techniques based on morphological critera is responsible for considerable limitations in the staging and surveillance of oral cancer. Therefore, this study investigates the contribution of [F18]-2-fluordesoxyglucose (FDG) positron emission tomography (PET) to tumor management with special regard to lymphnode involvement and therapeutic monitoring after radiotherapy. DESIGN: Prospective observational study. PATIENTS: Twenty-one patients with advanced oral cancer, predominantly T3/T4. INTERVENTION: FDG-PET scans before and after preoperative radio(chemo)therapy. Standardized uptake values (SUV) were determined for the tumor site and lymphnode areas. PET scans were correlated to histological findings after ablative tumor surgery. RESULTS: FDG-PET yielded superior sensitivity and specificity for tumor and lymphnode assessment. The effect of radiotherapy was reflected by the metabolic activity of the tumor, which shows a close correlation between the decrease of FDG uptake and histologic tumor regression. PET detected distant metastases and simultaneous tumors. CONCLUSION: FDG-PET is a challenging imaging technique with the potential to improve staging procedures for oral cancer. In the monitoring of metabolic activity of the tumor in the course of radio(chemo)therapy, FDG-PET allows objective measurement of the treatment response.

Aged↗
PubMed1998

Acquired colour deficiency in patients with Parkinson's disease.

The blue cone pathway is reported to be affected early in Parkinson's disease (PD) and acquired type three (tritan) defects may occur. Sixty-one patients attending a treatment and rehabilitation centre for PD were examined with clinical colour vision tests. Seven of 13 patients, for whom the diagnosis of PD was equivocal or who had other medical conditions, were identified as having tritan colour deficiency. Results for the remaining 44 PD patients were compared with 40 age matched controls. Ten PD patients (22.7%) had tritan defects. Tritan defects were not found in the control group but performance on some tests was age related. We conclude that clinical tests for tritan colour deficiency are unlikely to be helpful in identifying PD.

Aged↗
PubMed1998

Objective, noninvasive evaluation of velopharyngeal function in cleft and noncleft patients.

OBJECTIVE: The purpose of this study was to investigate a new diagnostic method that provides an approach to noninvasive, objective measurement of velopharyngeal movement by acoustic determination of epipharyngeal volume changes with velopharyngeal muscle function. DESIGN: This was a case control study, using consecutive samples. SETTING: This study took place at the Cleft Palate Rehabilitation Center of the University of Mainz, Germany. PATIENTS: Subjects were 29 consecutive cleft lip and palate (CLP) patients and 31 controls (21 patients with dysgnathia and 10 healthy volunteers). INTERVENTION: A series of transnasal acoustic measurements (pressure wave: 55 dB for 2 milliseconds) of epipharyngeal volume were performed with the pharyngeal muscles relaxed in end-expiration and while the velopharyngeal orifice was closed, with the difference in volume representing maximal pharyngeal movement. RESULTS: Cleft palate patients yielded significantly lower values of velopharyngeal movement (6.5 cm3) than did the control group (8.0 cm3) (p < .05; Mann-Whitney U test). Overlapping ranges of values were measured for the C(L)P and control groups. The least mobility (4.75 cm3) was measured in patients who had undergone pharyngeal flap surgery. Different patterns of restriction were observed in patients with and without a pharyngeal flap. CONCLUSION: Acoustic pharyngometry may provide access to noninvasive quantitative measurement of velopharyngeal movement and a better understanding of the pattern of movement in C(L)P-patients. We expect it to be a helpful tool in objectively monitoring the progress of logopedic therapy.

Acoustics↗
PubMed1997

[Acoustic reflection position monitoring of tracheal cannulae. A contribution to quality assurance?].

Non-invasive acoustic airway monitoring was evaluated in an experimental study. Recording amplitude and travel time of acoustic pulse response, an area-distance function of the cross sectional dimensions of the endotracheal tube and the adjacent airway was calculated to obtain an acoustic pattern of the airway. Measurements on models and excised human cadaver lungs were performed to discover whether displacement or obstruction of the artificial airway can be detected in the acoustic equivalent. Regression analysis revealed a close correlation between displacement of tracheostomy tubes and the shifting of the acoustic area-distance function (corr. coeff. 0.97-1). Dispersion analysis confirmed reasonable reliability (coeff. of variation 0.6-2.1%). Location and amount of obstruction could likewise be identified. Thus acoustic mapping provides an adequate approximation of the true geometry of tracheostomy and endotracheal tubes. We conclude that acoustic monitoring may provide a powerful tool to achieve primary prevention of airway disturbances in intubated and mechanically ventilated patients, as geometrical changes of airway configuration can be detected even before they cause substantial effects on respiratory metabolism.

Acoustics↗
PubMed1997

The influence of maxillary osteotomy on nasal airway patency and geometry.

Maxillary surgical repositioning affects nasal airway size. This study recorded nasal airway changes by acoustic rhinometry in patients with maxillary surgical repositioning after Le Fort I osteotomies. These changes were compared to the amount of skeletal movement by means of preoperative and 6-week postoperative lateral cephalography. Vertical linear movement of the posterior maxilla showed a very close relationship to volume changes in the posterior nasal segment. Anterior nasal volume changes can not be considered as a pure function of the direction and amount of skeletal movement. The greatest amount of cranial displacement tolerated without impaired nasal patency in this study was 7 mm.

Acoustics↗
PubMed1997

Acoustic monitoring of the artificial airway--experimental results.

Non-invasive acoustic airway-monitoring was evaluated in an experimental study. Recording amplitude and travel time of acoustic pulse response, an acoustic pattern of airway's geometry was then calculated. Measurements on models and excised human cadaver lungs were performed to discover whether displacement or obstruction of the artificial airway could be detected by its acoustic equivalent. Regression analysis revealed a close correlation between displacement of tracheostomy tubes and the shifting of the acoustic area-distance function (corr. coeff.: 0.97-1) and an adequate correlation between acoustic and planimetrical determination of cross-sectional area within the tubes (corr. coeff.: 0.78). Dispersion analysis confirmed reasonable reliability of acoustic cross-sectional measurements (Coefficients of variation: 0.6-2.1%). The acoustic mapping thus provides an excellent approximation of the true displacement and/or obstruction of tracheostomy and endotracheal tubes. We conclude that acoustic monitoring may provide a helpful tool for achieving an early warning system of airway disturbancies in intubated and mechanically ventilated patients, as geometrical changes of airway configuration may be detected before they lead to relevant effects on respiratory metabolism.

Acoustics↗
PubMed1997

[Standardized aerobic walking on the treadmill by healthy probands and patients with mitochondrial and non-mitochondrial myopathies].

Mitochondrial myopathies are characterized by an abnormal aerobic metabolism. The present study examines the serum lactate concentration during standardized aerobic treadmill ergometry and evaluates its relevance for the diagnosis of mitochondrial myopathies. The present study includes 50 volunteers without neuromuscular disorders (control group), 13 patients with mitochondrial, and 14 patients with non-mitochondrial neuromuscular disorders. All members of the control group were able to walk 15 minutes on the treadmill at a constant velocity of at least 5 km/h without exceeding the aerobic threshold (2 mMol/l lactate, venous blood). Ten patients with mitochondrial myopathies and 4 patients with non-mitochondrial myopathies already exceeded the aerobic threshold at walking velocities of 4 or 5 km/h. Though indicating a reduced aerobic endurance, a pathological test result does not prove the diagnosis of a mitochondrial myopathy. Sensitivity and specificity of treadmill ergometry did not differ significantly from those reported for bicycle ergometry. Thus, using the most common aerobic activity in daily life, treadmill ergometry can be considered as an alternative to bicycle exercise tests in the assessment of mitochondrial abnormalities.

Adult↗
PubMed1997

Nasal airway in cleft-palate patients: acoustic rhinometric data.

The objective of this study was to investigate an instrumental assessment technique for acquiring reproducible, metric data on the nasal airway in cleft-palate associated nasal dysplasia. A consecutive sample of 23 unilateral, 17 bilateral CLP patients and 15 controls with subjective normal nasal patency from a cleft-palate rehabilitation centre were studied. A series of transnasal acoustic measurements (pressure wave: 55 dB for 2 ms) of nasal volume were performed before and after topical decongestion with 2 x 0.3 mg of xylometazoline. A standardized regimen of acoustic parameters of the nasal valve and the adjacent segment of the nasal cavity were calculated. The cleft side yielded a significantly (40%) lower nasal volume than the non-cleft side. Considerably lower values were recorded for the isthmus of the cleft side (0.31 cm2) compared with the non-cleft side (0.52 cm2). Decongestion capacity was higher in the posterior segment, indicating cleft-side massive mucosal hypertrophy. In bilateral CLP, the isthmus measured 0.46 cm2. By decongestion, individual side differences were reduced in unilateral CLP patients but enhanced in bilateral clefts. The prevailing pattern of the cleft-side airway profile can be described as a 'descending W'. Acoustic rhinometry is a non-invasive, instrumental assessment technique for acquiring reproducible metric data of nasal dysplasia in cleft-palate patients. By identification of the location and amount of nasal obstruction, it provides topographic information about the individual airway profile. It is suitable for the longitudinal investigation of nasal-airway development, as well as the preparation and follow-up of corrective rhinosurgery.

Acoustics↗