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1.
Anal Bioanal Chem ; 416(15): 3555-3567, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703199

ABSTRACT

N-Acyl-homoserine lactones (AHL) play a major role in the communication of Gram-negative bacteria. They influence processes such as biofilm formation, swarming motility, and bioluminescence in the aquatic environment. A comprehensive analytical method was developed to elucidate the "chemical communication" in pure bacterial cultures as well as in the aquatic environment and engineered environments with biofilms. Due to the high diversity of AHLs and their low concentrations in water, a sensitive and selective LC-ESI-MS/MS method combined with solid-phase extraction was developed for 34 AHLs, optimized and validated to quantify AHLs in bacterial conditioned medium, river water, and treated wastewater. Furthermore, the developed method was optimized in terms of enrichment volume, internal standards, limits of detection, and limits of quantification in several matrices. An unanticipated variety of AHLs was detected in the culture media of Pseudomonas aeruginosa (in total 8 AHLs), Phaeobacter gallaeciensis (in total 6 AHLs), and Methylobacterium mesophilicum (in total 15 AHLs), which to our knowledge have not been described for these bacterial cultures so far. Furthermore, AHLs were detected in river water (in total 5 AHLs) and treated wastewater (in total 3 AHLs). Several detected AHLs were quantified (in total 24) using a standard addition method up to 7.3±1.0 µg/L 3-Oxo-C12-AHL (culture media of P. aeruginosa).


Subject(s)
Acyl-Butyrolactones , Rivers , Tandem Mass Spectrometry , Wastewater , Wastewater/microbiology , Wastewater/analysis , Acyl-Butyrolactones/analysis , Rivers/microbiology , Rivers/chemistry , Tandem Mass Spectrometry/methods , Bacteria/isolation & purification , Solid Phase Extraction/methods , Limit of Detection , Spectrometry, Mass, Electrospray Ionization/methods , Chromatography, Liquid/methods
2.
HNO ; 57(11): 1106-12, 2009 Nov.
Article in German | MEDLINE | ID: mdl-19727627

ABSTRACT

BACKGROUND: The genetic disease cystic fibrosis (CF) is characterised by reduced chloride secretion mediated by the cystic fibrosis transmembrane conductance regulator (CFTR) and Na(+) hyperabsorption through amiloride-sensitive epithelial sodium channels (ENaC). Mutations in CFTR cause the accumulation of thick mucus and dysfunction of mucociliary clearance in the respiratory tract. MATERIAL AND METHODS: In this project it was investigated whether Na(+) hyperabsorption is inhibited by the use of antisense oligonucleotides (AON). For functional analyses monolayers of human non-CF and CF nasal epithelial cells were measured in modified Ussing chambers. To analyse the AON effects on the protein level Western blotting analyses were carried out. RESULTS: AON transfection significantly inhibits Na(+) absorption via ENaC in non-CF and CF cells. Furthermore, Western blot analyses demonstrate a suppression of the ENaC protein in AON transfected human non-CF cells. CONCLUSION: The inhibition of ENaC associated Na(+) absorption by specific AON could offer a new perspective for the regulation of the Na(+) hyperabsorption in CF patients.


Subject(s)
Cystic Fibrosis/drug therapy , Cystic Fibrosis/physiopathology , Epithelial Sodium Channel Blockers , Nasal Mucosa/drug effects , Oligoribonucleotides, Antisense/pharmacology , Oligoribonucleotides, Antisense/therapeutic use , Sodium/metabolism , Amiloride/pharmacology , Blotting, Western , Cells, Cultured , Humans , Microscopy, Fluorescence , Oligoribonucleotides, Antisense/genetics , Sodium Channel Blockers/pharmacology , Transfection
3.
Acta Otolaryngol ; 126(1): 82-7, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16308259

ABSTRACT

CONCLUSIONS: Intraoperative CT surgery provides the surgeon with additional information about the altered surgical site in difficult anatomical situations. The skull base and lamina papyracea may be revealed by means of intraoperative CT, which may be beneficial in endonasal sinus surgery involving difficult surgical sites, although individual ethmoid cells cannot be assessed owing to blood artefacts. This provides the surgeon with valuable information that may facilitate the procedure considerably. In soft-tissue surgery it is advisable to apply a contrast agent in order to achieve good soft-tissue contrast, thus allowing the tumour to be adequately distinguished from benign tissue. The intraoperative application of CT is a fairly time-consuming procedure, partly owing to the preparation time (set-up of the appliance; 10-min warming-up phase) and partly due to the length of time required to calculate each image (15 s). OBJECTIVE: CT is a well-established imaging method for the assessment of osseous and soft-tissue structures in the head and neck region. Saving information and transferring it to the intraoperative site may, however, be problematic. Computer-assisted navigation systems are now able to assist difficult surgical procedures in the field of otolaryngology. To investigate the indications for intraoperative CT, we used it in various surgical procedures in the head and neck region. MATERIAL AND METHODS: Intraoperative CT was applied using the Tomoscan M in 46 cases in order to demonstrate the surgical benefit of the following procedures: endonasal surgical procedures on the paranasal sinuses (maxillary and ethmoidal sinusitis, anterior fracture of the sphenoidal sinus); tumour removal by means of laser surgery (carcinomas of the hypopharynx and larynx); and cochlear implantation (to verify the electrode position). After positioning the patient on the CT table, the workstation was set up in the operating theatre. If necessary, the gantry could be moved over the patient's head without repositioning the patient. RESULTS: Intraoperative CT was used to assist in the exposure of the skull base and lamina papyracea in endonasal surgery of the paranasal sinuses. Individual ethmoidal sinuses could not be evaluated owing to blood artefacts. Intraoperative imaging proved particularly helpful in revision surgery for chronic sinusitis in cases with missing anatomical landmarks owing to previous surgeries, where there is an increased risk of inflicting damage to the skull base or orbita. The resection margins can be determined in craniofacial resections. In soft-tissue procedures, such as tumour removal by means of laser surgery, it proved possible to visualize the resection borders of malignant tumours. Assessment of the electrode position in cochlear implantation is particularly useful in revision cases and in cases of cochlear obliteration.


Subject(s)
Intraoperative Care , Otorhinolaryngologic Diseases/diagnostic imaging , Otorhinolaryngologic Diseases/surgery , Otorhinolaryngologic Surgical Procedures/methods , Tomography, X-Ray Computed/methods , Cochlear Implantation/instrumentation , Cochlear Implantation/methods , Equipment Design , Humans , Image Processing, Computer-Assisted , Orbital Fractures/diagnostic imaging , Orbital Fractures/surgery , Otorhinolaryngologic Surgical Procedures/instrumentation , Paranasal Sinuses/diagnostic imaging , Paranasal Sinuses/surgery , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/surgery
4.
Acta Otolaryngol ; 126(10): 1084-90, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16923715

ABSTRACT

CONCLUSION: Tissue marking with soot-covered fine needles enables the optical coherence tomography (OCT) scanning plane to be localized within the histological specimen to an accuracy of approximately 50 microm. Tissue water content is an especially important parameter for in vitro measurements. Dehydration tends to produce an increase in surface reflections and a reduction in imaging depth. OBJECTIVES: The aim of this in vitro study was to evaluate parameters relevant to the visualization and conservation process to allow optimal images to be generated for later differentiation between healthy and degenerated tissue in vivo. MATERIALS AND METHODS: Various methods of marking samples were applied in vitro to achieve accurate overlaps of the OCT scanning plane and the corresponding section of the histological specimen. The influence of temperature and tissue water content was investigated using both porcine and human tissue. Samples were marked using fine needles, ablation craters generated by laser application, and colour markers introduced into the tissue. RESULTS: It was demonstrated that the water content of tissue exerts a direct influence on OCT imaging, whereas above 15 degrees C temperature had no effect on image quality. With regard to the marking of samples, the best results were obtained using sooted fine needles.


Subject(s)
Adipose Tissue/anatomy & histology , Muscle, Skeletal/anatomy & histology , Tomography, Optical Coherence/standards , Animals , Biopsy, Fine-Needle , Body Water/physiology , Humans , Image Enhancement , In Vitro Techniques , Magnetic Resonance Imaging , Needles , Soot , Sus scrofa , Temperature , Tomography, Optical Coherence/instrumentation
5.
Biochim Biophys Acta ; 1415(1): 114-24, 1998 Dec 09.
Article in English | MEDLINE | ID: mdl-9858704

ABSTRACT

Escherichia coli responds to K+-limitation or high osmolarity by induction of the kdpFABC operon coding for the high affinity K+-translocating KdpFABC complex. Expression of the corresponding operon is controlled by the membrane-bound sensor kinase KdpD and the cytoplasmic response regulator KdpE. Here, we examine the oligomeric state of KdpD. KdpD-His673-->Gln and KdpD-Asn788-->Asp are kinase inactive. When the corresponding genes are coexpressed, the resulting KdpD protein regains kinase activity in vitro, suggesting that the functional state of KdpD is at least a dimer and that the kinase reaction is a result of a trans-phosphorylation between two monomers. Furthermore, coexpression of kdpD-6His and kdpD-(Delta128-391) leads to stable heterooligomers that can bind to Ni-NTA agarose and that are coeluted. Purified and solubilized KdpD-6His has been electrophoresed in blue native polyacrylamide gels (BN-PAGE), and unphosphorylated and phosphorylated KdpD resulted in the same band pattern suggesting that the oligomeric state of KdpD does not change upon phosphorylation. In addition, determination of the molecular masses of KdpD-6His and KdpD-6His approximately 32P by gel filtration reveals a value of 245 kDa for both forms of the protein. The Stokes radius is determined to be 5.4 nm. Sucrose gradient sedimentation analysis of KdpD-6His results in a molecular mass of 289 kDa. The calculated molecular mass of a KdpD-6His monomer is 99.6 kDa. Considering the detergent bound to KdpD the obtained data reveal that KdpD is a homodimer and there is no change in the oligomeric state upon activation. Crosslinking experiments with single Cys KdpD molecules indicate that there is a close contact between the monomers in the transmitter as well as in transmembrane domain 1. BN-PAGE of solubilized and purified KdpD-6His devoid of Cys residues demonstrates that Cys residues do not contribute to the stabilization of the dimer.


Subject(s)
Bacterial Proteins/metabolism , Biosensing Techniques , Escherichia coli Proteins , Escherichia coli/enzymology , Protein Kinases/metabolism , Bacterial Proteins/isolation & purification , Chromatography, Gel , Dimerization , Electrophoresis, Polyacrylamide Gel , Molecular Weight , Mutagenesis, Site-Directed , Phosphorylation , Phosphotransferases/metabolism , Protein Kinases/isolation & purification
6.
Biochim Biophys Acta ; 1372(2): 311-22, 1998 Jul 17.
Article in English | MEDLINE | ID: mdl-9675324

ABSTRACT

Escherichia coli responds rapidly to K+-limitation or high osmolarity by induction of the kdpFABC operon coding for the high affinity K+-translocating Kdp-ATPase. This process is controlled by the membrane-bound histidine kinase KdpD and the response regulator KdpE. Here, it is demonstrated that replacements of the native Cys residues at positions 409, 852, and 874 influence distinct activities of KdpD, whereas replacements of Cys residues at positions 32, 256, and 402 have no effect. Replacements of Cys409 in KdpD reveal that transmembrane domain I is important for perception and/or propagation of the stimulus. When Cys409 is replaced with Ala, kdpFABC expression becomes constitutive regardless of the external stimuli. In contrast, when Cys409 is replaced with Val or Tyr, induction of kdpFABC expression in response to different stimuli is drastically reduced. KdpD with Ser at position 409 supports levels of kdpFABC expression comparable to those seen in wild-type. Since neither the kinase nor phosphatase activity of these proteins is affected, it is proposed that different amino acid side-chains at position 409 alter the switch between the inactive and active forms of the kinase. When Cys852 or Cys874 is replaced with Ala or Ser, kinase activity is reduced to 10% of the wild-type level. However, kinetic studies reveal that the apparent ATP binding affinity is not affected. Surprisingly, introduction of Cys852 and Cys874 into a KdpD protein devoid of Cys residues leads to full recovery of the kinase activity. Labeling studies support the idea that a disulfide bridge forms between these two residues.


Subject(s)
Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Cysteine , Escherichia coli Proteins , Escherichia coli/chemistry , Protein Kinases/chemistry , Protein Kinases/metabolism , Bacterial Proteins/genetics , Disulfides/analysis , Disulfides/chemistry , Kinetics , Liposomes , Mutagenesis, Site-Directed , Phosphorylation , Polymerase Chain Reaction , Protein Kinases/genetics , Signal Transduction , Structure-Activity Relationship
7.
Biosystems ; 78(1-3): 23-37, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15555756

ABSTRACT

A mathematical model for the KdpD/KdpE two-component system is presented and its dynamical behavior is analyzed. KdpD and KdpE regulate expression of the kdpFABC operon encoding the high affinity K+ uptake system KdpFABC of Escherichia coli. The model is validated in a two step procedure: (i) the elements of the signal transduction part are reconstructed in vitro. Experiments with the purified sensor kinase and response regulator in presence or absence of DNA fragments comprising the response regulator binding-site are performed. (ii) The mRNA and molecule number of KdpFABC are determined in vivo at various extracellular K+ concentrations. Based on the identified parameters for the in vitro system it is shown, that different time hierarchies appear which are used for model reduction. Then the model is transformed in such a way that a singular perturbation problem is formulated. The analysis of the in vivo system shows that the model can be separated into two parts (submodels which are called functional units) that are connected only in a unidirectional way. Hereby one submodel represents signal transduction while the second submodel describes the gene expression.


Subject(s)
Escherichia coli Proteins/metabolism , Escherichia coli/metabolism , Protein Kinases/metabolism , Signal Transduction , Trans-Activators/metabolism , Base Sequence , DNA Primers
8.
Acta Otolaryngol ; 121(8): 973-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11813906

ABSTRACT

Minimally invasive surgical procedures have revolutionized surgery of the paranasal sinuses. The endonasal procedure has become standard practice due to a better understanding of pathological physiology. However, malformations, previous operations and bleeding can interfere greatly with intraoperative orientation. Together with microscopy and endoscopy, image-guided surgery has the potential to be of significant assistance to the surgeon. We evaluated the electromagnetic navigation system InstaTrak 2000 (Visualization Technologies Inc., Lawrence, MA) in 168 patients with various disorders of the paranasal sinuses who underwent endonasal surgery. The system consists of a headset attached to an electronic transmitter which is fitted on the dorsum of the nose and in the external auditory canal. With the aid of low-frequency magnetic fields the position of the instrument equipped with an electromagnetic receiver is calculated on the basis of the reaction of ferromagnetic components in the magnetic field; the location is displayed in orthogonal sections on a high resolution screen. The intraoperative accuracy of the system was estimated to be 1.2-2.8 mm. The preparation time amounted to < 10 min. No system failures were observed. The InstaTrak 2000 navigation system is only suitable for endonasal surgery. The placement of the electromagnetic transmitter and receiver allows flexible head positioning through the use of a headset. This system is a valuable aid for the surgeon under anatomically complex conditions. The technology also lends itself well to training purposes, as visualization in different sectional planes augments the understanding of anatomy and pathological anatomy.


Subject(s)
Skull Base/surgery , Surgery, Computer-Assisted/instrumentation , Adult , Aged , Equipment Design , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Skull Base/pathology , Surgery, Computer-Assisted/methods
9.
Skull Base ; 11(4): 277-85, 2001 Nov.
Article in English | MEDLINE | ID: mdl-17167630

ABSTRACT

The introduction of computer-assisted navigation systems has played a significant role in assuring the integration and consistent intraoperative use of radiological information. We used a frameless stereotactic navigation system to treat 62 patients with a variety of skull base pathologies. The optoelectric appliance uses digital imaging information to locate surgical instruments in the operative area. The aim of this study was to evaluate the clinical accuracy, practicality, and impact of this navigation system on otolaryngological procedures. In conjunction with rigid head fixation and bone-anchored registration markers, the precision of registration was 0.8 mm and the accuracy of clinical measurements was less than 2 mm. With conventional fiducials and flexible head positioning, deviations were as large as 4.5 mm. The additional use of surface registration increased the precision of registration. Preoperative preparations took 15 to 35 minutes, depending on the complexity of the planning. Intraoperative computer support is an important aid to a surgeon's orientation, especially when a patient's anatomy is atypical. Navigation systems will likely improve the quality of surgery and facilitate training.

10.
Comput Aided Surg ; 4(5): 275-80, 1999.
Article in English | MEDLINE | ID: mdl-10581525

ABSTRACT

PURPOSE: To quantify the contribution of a computed tomography (CT) scan to navigation accuracy in computer-assisted surgery. METHODS: Eighty-eight patients undergoing computer-assisted facial or skull-base surgery were fitted preoperatively with 4 to 12 markers, either attached to the skin (n = 20) or fixed in the osseous skull (micro-screws; n = 68). Low-dose high-resolution spiral CT was achieved with 25-cm field of view (FoV), 1-mm slice thickness, 2-mm table increment, 1-mm reconstruction interval, 140 kV, 40 mA, bony reconstruction algorithm, and 180 degrees reconstruction profile (effective slice thickness = 1.8 mm). During surgery, navigation accuracy was evaluated using two navigation systems. RESULTS: Mean error was 0.66 mm for osseous markers and 1.58 mm for cutaneous markers. Both values are markedly smaller than the effective slice thickness of the scan protocol used. Radiation exposure of the patient for the entire examination never exceeded that necessary for one single 10-mm slice in a standard brain examination. Despite the reduced dose, landmarks and fiducials were precisely identified in all cases. CONCLUSIONS: The CT-induced positioning error in the Z-axis is considerably reduced by overlapping raw data reconstruction. For 1-mm slices and a 25-cm FoV, the average scan-induced positioning error is about 0.3 mm. Spatial resolution is not affected by the low dose applied. For MRI-based navigation, a 1 mm3 voxel size is the best compromise between signal-to-noise ratio, spatial resolution and scan time.


Subject(s)
Face/surgery , Skull Base/surgery , Therapy, Computer-Assisted , Tomography, X-Ray Computed/methods , Algorithms , Bone Screws , Face/diagnostic imaging , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging , Prospective Studies , Radiation Dosage , Radiographic Image Enhancement , Signal Processing, Computer-Assisted , Skin , Skull Base/diagnostic imaging , Therapy, Computer-Assisted/instrumentation , Tomography, X-Ray Computed/instrumentation
11.
Cochlear Implants Int ; 5(4): 146-59, 2004 Dec.
Article in English | MEDLINE | ID: mdl-18792210

ABSTRACT

BACKGROUND: Successful outcomes of cochlear implantation in children have led to a gradual reduction in the age at which implantation is performed. Now that newborn hearing screening and a reliable audiological diagnostic procedure are well established, the question has been raised as to whether implantation before the age of 1 year is effective and safe. MATERIAL AND METHOD: The study included 27 children implanted before the age of 1 year (group 1) and 89 children implanted between the ages of 1 and 2 years (group 2). Patient-related data were analysed with respect to individual anamnesis, implantation, rehabilitation and speech understanding. RESULTS: Irrespective of the children's age, the incidence of surgical or anaesthesiological complications did not increase. After two years, group 1 demonstrated better results in terms of development of hearing and speech understanding. These results correlated more closely with the children's actual age than with the length of time in rehabilitation. CONCLUSION: This study revealed that children implanted before the age of 1 year were subjected to no additional risks and showed superior development of speech understanding. Cochlear implantation should therefore be performed in very young children identified as suffering from profound bilateral hearing loss.

12.
Article in English | MEDLINE | ID: mdl-16785185

ABSTRACT

This is a prospective study on 808 profoundly or totally deaf patients who underwent either unilateral or bilateral cochlear implantation, involving a minimally invasive surgical approach, at the Medical University of Hannover's Department of Otolaryngology between May 2001 and May 2005. Advanced Bionics, Cochlear and MED-EL devices were used, the latter having been in use at our department since the beginning of 2003. The aim of our investigation was to determine the optimal surgical technique, evaluate safety aspects and gauge patient satisfaction with this minimally invasive surgical approach during cochlear implantation. Surgical technique is analysed. Complications such as skin flap problems did not occur. The use of this minimally invasive surgical technique did not increase the surgical risk. This procedure proved both cosmetically and psychologically beneficial for patients, especially for children and their parents.


Subject(s)
Cochlear Implantation/methods , Deafness/therapy , Minimally Invasive Surgical Procedures , Adult , Child , Cochlear Implants , Equipment Design , Follow-Up Studies , Humans , Prospective Studies , Suture Techniques , Treatment Outcome
13.
HNO ; 54(7): 565-72, 2006 Jul.
Article in German | MEDLINE | ID: mdl-15841407

ABSTRACT

BACKGROUND: The success of cochlear implants in children was followed by a stepwise reduction in age at time of surgery. As a result of newborn hearing-screening (NHS) and the reliable audiologic diagnostic procedure, the question is raised as to whether an implantation before the age of 1 year is effective and safe in terms of surgery and rehabilitation. METHOD AND PATIENTS: This retrospective study included 27 children implanted before the age of 1 year (Gr. 1) and 89 children implanted between the age of 1 and 2 years (Gr. 2). Patient related data were analysed for individual history, surgery, rehabilitation and speech understanding. RESULTS: The incidence of complications was not increased in Gr. 1. The fitting of a speech processor was effective and uneventful in all children. The development of hearing and speech understanding showed better results after 2 years in Gr. 1. This development is more obvious for absolute age and not to rehabilitation time. CONCLUSION: In order to achieve an optimal timing for the development of speech understanding, cochlear implantation should be performed before the age of 2 years. This study revealed no additional risks for children in Gr. 1, but the development of speech understanding was better. As a consequence, cochlear implantation should be considered for very young children with an identified bilateral profound hearing loss.


Subject(s)
Cochlear Implants , Deafness/rehabilitation , Pediatrics/methods , Cochlear Implantation , Female , Humans , Infant , Infant, Newborn , Male , Pilot Projects , Recovery of Function , Retrospective Studies , Time Factors , Treatment Outcome
14.
Eur J Anaesthesiol ; 22(9): 678-82, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16163914

ABSTRACT

BACKGROUND AND OBJECTIVE: Since the introduction of the laryngeal mask into clinical practice, various additional supraglottic ventilatory devices have been developed. Although it has been demonstrated that the laryngeal tube is an effective airway device during positive pressure ventilation no clinical study has been performed thus far regarding its use in patients with predicted ventilation and intubation difficulties. METHODS: The aim of this study was to prospectively evaluate the use of the laryngeal tube for temporary oxygenation and ventilation in adult patients with supraglottic airway tumours scheduled to undergo a pharyngeal-laryngeal oesophagoscopy and bronchoscopy under general anaesthesia. In addition to our standard airway management with face mask ventilation and rigid bronchoscopy, all patients were temporarily ventilated with an laryngeal tube. Also, in patients requiring laryngeal biopsies, endotracheal intubation was performed with a 6.0 mm microlaryngeal tracheal tube. Minute ventilation volumes, tidal volumes, ventilation pressures, end-expiratory CO2 concentration, oxygen saturation and arterial blood gas samples were measured. RESULTS: From 54 enrolled patients only patients with relevant tumour masses were evaluated (n = 23). Mask ventilation was performed without difficulty in 15 of 23 patients. Mechanical ventilation with the laryngeal tube was possible in 22 of 23 patients with an audible leak present in three. Conventional endotracheal intubation was successfully performed in 19 of 23 patients. During face mask ventilation, minute volume, tidal volume, ventilation pressure, end-tidal CO2, oxygen saturation and arterial PO2 were significantly lower and PCO2 significantly higher (P < 0.05, paired t-test). No statistically significant differences were noted between the laryngeal tube and the microlaryngeal tracheal tube. CONCLUSIONS: The possibility of difficult ventilation and intubation must always be considered, in patients with supraglottic airway tumours. In these cases, the laryngeal tube can be considered for routine airway management and may be useful in the 'cannot-intubate' situation although difficulties should be anticipated in patients with previous irradiation, specifically of the throat area.


Subject(s)
Laryngeal Masks , Laryngeal Neoplasms/physiopathology , Pharyngeal Neoplasms/physiopathology , Respiration, Artificial , Adult , Biopsy , Bronchoscopy , Carbon Dioxide/analysis , Esophagoscopy , Female , Humans , Intubation, Intratracheal/instrumentation , Male , Masks , Middle Aged , Oxygen/blood , Oxygen Consumption/physiology , Pressure , Prospective Studies , Pulmonary Ventilation/physiology , Tidal Volume/physiology
15.
Allergy ; 60(3): 354-9, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15679722

ABSTRACT

BACKGROUND: Loteprednol etabonate (LE) is a novel soft steroid that was designed to improve the benefit/risk ratio of topical corticosteroid therapy. This study assesses the clinical efficacy and safety of three different doses of LE nasal spray in seasonal allergic rhinitis (SAR). METHODS: In this single-center, double-blind, placebo-controlled, parallel-group trial 165 subjects with SAR to grass pollen received daily single doses of either 100, 200, 400 microg LE nasal spray, or placebo for 14 days. The patients underwent three 4-h allergen challenges with grass pollen in an environmental exposure unit at a screening visit (baseline) and on days 7 and 14 of treatment. Standardized nasal symptom scores were obtained every 20 min. Nasal flow, nasal secretions, and FEV(1) were measured every hour during allergen challenges. RESULTS: After 14 days of treatment, patients who received 400 microg LE had significantly lower total nasal symptom scores compared with those receiving placebo (P = 0.007). LE400 reduced rhinorrhea, nasal congestion, nasal itching, the amount of nasal secretions, and improved nasal flow as compared with placebo (P < 0.05). LE100 and LE200 were not significantly different from placebo. All treatments were well tolerated. CONCLUSIONS: Loteprednol 400 microg once daily is superior to placebo and the only effective dose tested in improving nasal symptoms and objective parameters in patients with SAR.


Subject(s)
Allergens/immunology , Androstadienes/administration & dosage , Anti-Allergic Agents/administration & dosage , Environmental Exposure , Rhinitis, Allergic, Seasonal/drug therapy , Rhinitis, Allergic, Seasonal/immunology , Administration, Intranasal , Adult , Aerosols , Androstadienes/adverse effects , Androstadienes/therapeutic use , Anti-Allergic Agents/adverse effects , Anti-Allergic Agents/therapeutic use , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Loteprednol Etabonate , Male , Middle Aged , Rhinitis, Allergic, Seasonal/physiopathology , Suspensions , Treatment Outcome
16.
J Biol Chem ; 275(22): 17080-5, 2000 Jun 02.
Article in English | MEDLINE | ID: mdl-10747873

ABSTRACT

The putative turgor sensor KdpD is characterized by a large, N-terminal domain of about 400 amino acids, which is not found in any other known sensor kinase. Comparison of 12 KdpD sequences from various microorganisms reveals that this part of the kinase is highly conserved and includes two motifs (Walker A and Walker B) that are very similar to the classical ATP-binding sites of ATP-requiring enzymes. By means of photoaffinity labeling with 8-azido-[alpha-(32)P]ATP, direct evidence was obtained for the existence of an ATP-binding site located in the N-terminal domain of KdpD. The N-terminal domain, KdpD/1-395, was overproduced and purified. Although predicted to be hydrophilic, it was found to be membrane-associated and could be solubilized either by treatment with buffer of low ionic strength or detergent. The membrane-associated form, but not the solubilized one, retained the ability to bind 8-azido-[alpha-(32)P]ATP. Previously, it was shown that the phosphatase activity of a truncated KdpD, KdpD/Delta12-395, is deregulated in vitro (Jung, K., and Altendorf, K. (1998) J. Biol. Chem. 273, 17406-17410). Here, we demonstrated that this effect was reversed in vesicles containing both the truncated KdpD and the N-terminal domain. Furthermore, coexpression of kdpD/Delta12-395 and kdpD/1-395 restored signal transduction in vivo. These results highlight the importance of the N-terminal domain for the function of KdpD and provide evidence for an interaction of this domain and the transmitter domain of the sensor kinase.


Subject(s)
Bacterial Proteins/metabolism , Escherichia coli Proteins , Escherichia coli/enzymology , Protein Kinases/metabolism , Adenosine Triphosphate/metabolism , Amino Acid Sequence , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Molecular Sequence Data , Mutagenesis, Site-Directed , Photoaffinity Labels , Protein Binding , Protein Kinases/chemistry , Protein Kinases/genetics , Sequence Homology, Amino Acid
17.
Laryngorhinootologie ; 83(3): 164-72, 2004 Mar.
Article in German | MEDLINE | ID: mdl-15042481

ABSTRACT

BACKGROUND: The local therapy of inner ear diseases provides a means of directly applying pharmacological substances and delivering electrical stimulation to inner ear structures. Problems relating to dosage, systemic effects and the blood-cochlear barrier are thus avoided, which is not the case with systemic therapy. The preferred access point is the membrane of the round window. PATIENTS AND METHODS: An appropriately shaped catheter (DURECT Corporation, Cupertino, CA, USA), whose double-lumen passage system permits the variation of concentration and flow, is inserted into the round window niche. In a prospective, placebo-controlled clinical study, this application system was tested in 20 patients with chronic tinnitus. Following implantation the substances lidocaine, glutamate, glutamic acid and caroverine were applied via an attached external micropump. RESULTS: The values for tinnitus loudness, level of irritation caused by the tinnitus and subjective effectiveness of the therapy - measured by means of the visual analog scale (VAS) - showed no significant change, although the most marked improvement was indicated for caroverine. CONCLUSIONS: These results indicate that a positive effect was observable only in a proportion of the patients. Continuous therapy of tinnitus and inner ear diseases will only be possible once a totally implantable microdosage system has been developed.


Subject(s)
Catheters, Indwelling , Ear, Inner/drug effects , Glutamic Acid/administration & dosage , Infusion Pumps , Lidocaine/administration & dosage , Quinoxalines/administration & dosage , Round Window, Ear/drug effects , Tinnitus/drug therapy , Administration, Topical , Adult , Aged , Auditory Threshold/drug effects , Chronic Disease , Endoscopy , Female , Humans , Loudness Perception/drug effects , Male , Middle Aged , Pain Measurement , Patient Satisfaction , Treatment Outcome
18.
HNO ; 50(3): 244-7, 2002 Mar.
Article in German | MEDLINE | ID: mdl-11975081

ABSTRACT

The differential diagnosis of patients with ulcerative trachelophyma repeatedly causes difficulties. Particularly in view of the possibly fatal outcome, early differentiation between two clinical pictures is very important. Necrotizing fasciitis is often misdiagnosed or the diagnosis is delayed with a mortality rate of approximately 25-40%. It is characterized by local disintegration of the subcutaneous fascia and extensive gangrene of the skin. Sometimes it is not even possible to control the disease using combined antibiotics. Early surgical exploration is mandatory to stop progression of the disease. Pyoderma gangrenosum develops following an initial lesion with pustules and bullae in an ulceration with slight bleeding. Therapy consists of i.v. glucocorticoids (60-200 mg prednisolone/day) administered as early as possible. In complete contrast to the therapy for necrotizing fasciitis, surgical intervention should be strictly avoided in cases of pyoderma gangrenosum.


Subject(s)
Fasciitis, Necrotizing/diagnosis , Neck , Pyoderma Gangrenosum/diagnosis , Adult , Diagnosis, Differential , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Patient Care Team , Prednisolone/administration & dosage , Pyoderma Gangrenosum/drug therapy , Tomography, X-Ray Computed
19.
Laryngorhinootologie ; 82(9): 632-44, 2003 Sep.
Article in German | MEDLINE | ID: mdl-14517759

ABSTRACT

Few of the pioneering manufacturers who attempted to develop navigation systems have been able to establish themselves within the market long-term. The same applies to the technological basis of these systems which aid intraoperative anatomical orientation. The first few systems registered the mechanical displacement of the navigational instrument's axes. Optoelectronic and electromagnetic methods are now prevalent. In contrast to electromagnetic systems, the "line of sight" between the camera system, the reference markers placed on the patient's head and the navigation instruments must remain unobstructed during the navigation process when using electrooptical navigation systems. Whereas, in the past, only preoperative CT scans were used for navigation, the integration of MRI and sonography--whose images can now be fused with each other and with those provided by other intraoperative imaging techniques such as fluoroscopy and endosonography--has become increasingly popular. Navigation systems require input of information about spatial conditions. This is carried out via procedures of registration and referencing, by means of which the relative position of reference markers at the head of the patient is correlated with the image data. The equipment is calibrated in the same way. Headsets, headbands and bone-anchored adapters are available for the fixation of the markers in the patient's head. Whereas the use of a headband or headset requires considerably less time, bone-anchored referencing increases the precision of the navigation system. The surgeon must be able to manage the different methods. In order to reduce the time required for preoperative preparation and to enhance the handling of the navigation processor for the surgeon, it is essential to have a clear menu. The surgeon is able to plan the steps involved in the surgery using the processor, define the access to the surgical site and control the surgery intraoperatively. Preoperative segmentation of functionally and clinically relevant structures enables minimally invasive surgery to be carried out, such as procedures with the aim of acquiring biopsy tissue and the search for foreign bodies. Following the technical development of the systems, the manufacturers are endeavouring to simplify their handling in close coordination with the users. The next step has to be the clinical evaluation of the navigation systems in accordance with the EBM standard, in order to establish this assistive method as routine clinical practice while applying meaningful medical criteria.


Subject(s)
Evidence-Based Medicine , Otorhinolaryngologic Diseases/surgery , Skull Base/surgery , Surgery, Computer-Assisted , Endosonography , Fluoroscopy , Humans , Magnetic Resonance Imaging , Surgery, Computer-Assisted/instrumentation , Tomography, X-Ray Computed , Ultrasonography
20.
Laryngorhinootologie ; 75(1): 59-62, 1996 Jan.
Article in German | MEDLINE | ID: mdl-8851123

ABSTRACT

BACKGROUND: Surgeons should thoroughly consider the clinical implications of elective surgery such as septorhinoplasty for functional and cosmetic improvement of the appearance of the nose. Complications may jeopardize the intended result of this surgery. CASE REPORT: We report on the rare complication of devitalization of two incisors in the maxilla with disturbing discoloration after performing a septorhinoplasty in a 23-year-old woman. The patient underwent a serial hydrogen peroxide bleaching and a root canal procedure. CONCLUSION: The osteotomy of a huge basal crista that compromised neurovascular dental supply could be a possible mechanism of this event. Even though such a complication after septorhinoplasty is extremely rare, patients should be informed of this eventually prior to surgery, if only for legal reasons.


Subject(s)
Nasal Septum/surgery , Postoperative Complications/etiology , Rhinoplasty , Tooth Discoloration/etiology , Adult , Female , Humans , Incisor/blood supply , Incisor/innervation , Ischemia/etiology , Postoperative Complications/therapy , Tooth Bleaching , Tooth Discoloration/therapy
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