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Biomedical subjects

H P Weber

Publications and source records attributed to H P Weber.

At least 19 recordsLinked to original sources

Advantages and dangers of erbium laser application in stapedotomy.

Among different types of lasers, the erbium laser exhibits particularly favourable characteristics for ear surgery. Experiments with application of erbium laser pulses to the isolated stapes connected to an inner ear model confirmed that there was virtually no thermal effect to the inner ear liquid and that the border damage zone on the stapes footplate perforation did not exceed 5-10 microm. Erbium laser pulses, however, produce pressure waves due to the explosive ablation of tissue. Pulses of 10 to 17 J/cm2 producing pressure waves between 140 and 160 dB appear to be a limit for clinical application. With these criteria, an in-house built erbium YAG laser with a fiberoptic delivery device was used in 15 patients for stapedotomy. A special microhandpiece, where a zirconium fluoride fiber was connected to a quartz tip, was developed. In addition, three patients had stapedotomy with a commercially available Zeiss (Opmi TwinER) microscope equipped with a micromanipulator-operated erbium laser beam. One year after surgery, the air-bone gap was closed in all patients to within 20 dB between 0.5 and 3 kHz with only minor permanent bone conduction threshold losses (< 20 dB). However, we observed an immediate postoperative middle and high frequency loss of up to 75 dB on bone conduction threshold measurements 2 h after surgery, suggesting an acoustic traumatization by the erbium laser. This threshold shift recovered close to preoperative values within 6 h. These observations prompted us to discontinue the clinical use of erbium laser for stapedotomy until the problem of temporary acoustic traumatization is resolved.

Adult

Microbiota of successful osseointegrated dental implants.

BACKGROUND: The long-term survival of dental implants depends, in part, on control of bacterial infection in the peri-implant region. Periodontal pathogens colonized implants symptomatic through infection, whereas the microbiota of successful implants was similar to that of periodontal health. This study examined the impact on the peri-implant microbiota of crown restorations; implant type; length of time of loading; history of implant or periodontal infections; and whether implants replaced single or multiple teeth. It was of particular interest to evaluate implant colonization by species in a newly described red complex of periodontal pathogens, Porphyromonas gingivalis and Bacteroides forsythus. METHODS: This study sampled 43 partially edentulous subjects with successfully osseointegrated titanium root-form dental implants. Eighty-one (81) non-submerged and 20 submerged asymptomatic implants, 83 crowned, and 36 uncrowned teeth were sampled from peri-implant or subgingival sites. The microbiota of samples was evaluated using whole genomic DNA probes in a checkerboard assay to 23 subgingival species. RESULTS: Implants were colonized principally by oral streptococci, capnocytophagae, Veillonella parvula, Peptostreptococcus micros, and Fusobacterium nucleatum. The periodontal species, P. gingivalis, B. forsythus, Prevotella intermedia, Prevotella nigrescens, and Campylobacter rectus were detected in a few subjects. The microbiota around crowned implants and crowned teeth was similar. Streptococcus oralis, P. intermedia, and Selenomonas noxia were elevated in samples from uncrowned teeth compared to crowned teeth and implants. Microbial complexity increased as loading time increased, but colonization by periodontal pathogens, including red complex species, was higher in subjects with previous periodontal disease. No differences were observed in the microbiota of 1- and 2-stage implants, or between implants supporting single or multiple restorations. CONCLUSIONS: While presence of crowns had only a minor impact on the peri-implant microbiota, microbial changes were observed the longer the implants had been in function and in those patients with a history of periodontal or peri-implant infections. A history of periodontitis had a greater impact on the peri-implant microbiota than implant loading time. The major influence on the peri-implant microbiota was, however, the microbiota on remaining teeth. P. gingivalis and B. forsythus, red complex periodontal pathogens, colonized several implants, although all implants were successfully osseointegrated.

Adult

A radiographic evaluation of bone healing around submerged and non-submerged dental implants in beagle dogs.

BACKGROUND: The rehabilitation of the oral cavity with dental implants has become a predictable treatment modality. However, there have been only a few direct comparisons evaluating the submerged and nonsubmerged placement techniques. The purpose of this study was to characterize radiographic peri-implant bone changes following the insertion of submerged and nonsubmerged implants in the beagle dog. METHODS: At the end of the extraction healing phase, 19 submerged and 19 nonsubmerged implants were randomly placed in a split-mouth study design and observed over an 18-week period. For submerged implants, a second stage surgery and transmucosal abutment attachment was performed at week 12. Standardized dental radiographs taken at baseline, week 12, and week 18 were used to measure peri-implant bone changes. The radiographs were analyzed with a simple computer assisted method. RESULTS: A total of 43 standardized radiographs were exposed to evaluate the 38 implants. During the study period, all submerged and nonsubmerged implants demonstrated peri-implant bone loss. At baseline, both submerged and nonsubmerged implants had similar bone levels (P > or = 0.05). When the mean peri-implant bone levels for submerged and nonsubmerged implants were compared from baseline to week 12, nonsubmerged implants had a significantly greater amount and rate of bone resorption than submerged implants (P < or = 0.05). Following week 12, the initially submerged implant had a significantly higher rate and amount of peri-implant bone loss than the nonsubmerged implants (P < or = 0.05). However, by the end of the study period, week 18, both submerged and nonsubmerged implants had comparable bone levels (P > or = 0.05). CONCLUSIONS: The study indicates that, although the temporal patterns of peri-implant bone resorption differed, there were no differences between submerged and nonsubmerged implants in the overall amount and rate of peri-implant bone loss.

Alveolar Process

Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations.

T-cell immunosuppressant-based therapies efficiently control early graft rejection in allotransplantation settings. They fail, however, to prevent those rejection events which are mediated by transplant-induced antibody (Ab) responses such as those involved in xenograft and chronic allograft rejection. This is mainly due to their inability to block T-cell-independent Ab production against the transplanted organs. The bioactive metabolite 2(Z) of leflunomide (1) inhibits the formation of such Ab, but the drug has pharmacokinetic properties and a therapeutic window incompatible with transplantation indications. Pyrazole 3, a constrained analogue of 2(Z), was designed and shown to be conformationally and biologically similar to 2(Z). Further investigations with derivatives of 3 demonstrated that the pyrazoles had very tight structure-activity relationships, the only equipotent compound being 3o. However, in contrast to 2(Z), both 3 and 3o were inactive in vivo due to short half-life and drug concentrations lower than the in vitro obtained IC50 values. Compound 3o inhibits T-cell-independent Ab production by a different biochemical mechanism from that of 2(Z) and 3 and may therefore represent a valuable tool for the identification of new targets for B-cell inhibition.

Administration, Oral

Laser catheter coagulation of normal and scarred ventricular myocardium in dogs.

BACKGROUND AND OBJECTIVE: Larger lesions would increase success rates of catheter ablation of ventricular arrhythmias. Therefore, improved radio frequency current application techniques, but also alternative energy sources, are being investigated. The purpose of this study was to determine morphology and dimensions of ventricular lesions induced by transcatheter application of laser energy. MATERIAL AND METHODS: A total of 244 lesions were produced by Nd:YAG laser pulses, 1,064 nm, 10-30 W, 15-60 s, percutaneously (endocardial approach, n = 124) and under visual control (epicardial approach, n = 120) in the left ventricular walls of 24 anesthetized dogs. RESULTS: Dimensions of lesions increased with the amount of energy applied. Maximal values were obtained at 20 W, 60 s: depth = 12.6 +/- 1.1 mm (transmural); width = 15.0 +/- 2.8 mm; volume = 1,582 +/- 777 mm3. Volumes of lesions did not change significantly when induced through previously scarred myocardium. Histologically, lesions were clear-cut, without crater or thrombus formation. Procedures and follow-up periods of up to 22 months were without complications. CONCLUSION: Nd:YAG laser pulses at 10-20 W and 15-60 s produce homogeneous myocardial lesions of coagulation necrosis of reproducible sizes, in a controllable manner, without unwanted effects on the ventricular walls, in normal and through scarred myocardium of dogs. The laser method is a promising alternative for ablation of ventricular arrhythmias including candidates with ischemic heart disease.

Animals

Computer-assisted milling of dental restorations using a new CAD/CAM data acquisition system.

BACKGROUND: Recent technologic innovations have created possibilities for restorative dentistry, such as computer-aided design and computer-aided manufacturing (CAD/CAM). PURPOSE: This article presents a new CAD/CAM process that has been developed for the fabrication of dental restorations. METHODS: This process uses an improved imaging technique, successfully applied in other industries. Imaging is accomplished with 2-dimensional line grids projected onto an object, which allows for a mathematical reproduction of prepared and unprepared tooth surfaces, including those that are outside the direct line of light. The relative position of the sensor to the surface of the object is controlled automatically. CONCLUSIONS: This system, which is undergoing clinical testing, allows the generation of various types of highly accurate dental restorations (inlays, onlays, crown, and fixed partial dentures) from a number of different materials. Acquired digitized data points are directly translated from the sensor to the electronic controls of the milling machine to provide various manufacturing possibilities, including copy milling and accurate reproduction of occlusal tooth surfaces in various materials.

Computer-Aided Design

The soft tissue response to osseointegrated dental implants.

The use of dental implants in the treatment of fully edentulous patients has become an important addition in oral/dental rehabilitation. The fact that these implants penetrate the oral mucosa can lead to the assumption that peri-implant tissues, similar to the periodontal tissues, are fulfilling an important function as a barrier to protect the bony anchorage underneath. It has been shown that insufficient plaque removal may lead to peri-implant tissue disease with bone loss similar to teeth. However, it is unclear how important this cause is as a source of implant failure compared with other factors, such as inadequate bone healing, unfavorable quantity and quality of bone, or (bio)mechanical and functional problems. It is also not understood if peri-implant epithelium and connective tissue are equally needed and/or qualified to slow down or prevent tissue breakdown as their periodontal counterparts. The scientific work focusing on peri-implant soft tissues has dramatically increased in the past few years. Most studies to date have examined and described their structure but little data exist on their true biologic function. This review analyzes the current understanding of morphologic and clinical features of the peri-implant soft tissues. Furthermore, evidence shall be provided that peri-implant soft tissues do not interfere with the current favorable results obtained when treating the edentulous patient with osseointegrated implants.

Alveolar Bone Loss

Transcatheter endomyocardial laser revascularization: a feasibility test.

By means of a special catheter system, a total of 76 endomyocardial laser channels were percutaneously produced in a controllable manner at selected sites in 6 beating canine hearts. Acute patency of channels (length = 4-11 mm, diameter = 0.5-1.2 mm) was documented angioscopically and histologically. This minimally invasive method might be useful for revascularising certain patients with ischemic heart disease without resorting to open-chest surgery.

Angioscopy

Guided bone regeneration utilizing expanded polytetrafluoroethylene membranes in combination with submerged and nonsubmerged dental implants in beagle dogs.

Treatment of partial and total edentulism with submerged and nonsubmerged dental implants which follows the concept of osseointegration has become an accepted treatment modality. With compromised implant sites, practitioners have begun to combine one-stage implants with established techniques including guided bone regeneration. However, the clinical evaluation of this technique is limited. Therefore, the purpose of this study was to evaluate osseointegration and bone regeneration around nonsubmerged or submerged implants placed directly into surgically created osseous defects with or without expanded polytetrafluoroethylene (ePTFE) membranes. A total of 24 implants were placed in the mandibles of 4 beagle dogs and randomly assigned to 1 of 3 treatment groups. In group A, nonsubmerged implants were placed into osseous defects and treated with a poncho style ePTFE membrane. These membranes had a hole punched into the center and were slipped over the nonsubmerged implants. In group B, nonsubmerged implants were placed into osseous defects without an ePTFE membrane. In group C, submerged implants were placed into osseous defects and covered with an ePTFE membrane. Histometric measurements of each treatment group were made to determine percent bone gain or loss along the implant surface. Although a number of membrane removals occurred during the healing period, histological analysis indicated osseous ingrowth and osseointegration around nonsubmerged and submerged implants. An overall comparison of the treatment groups with ANOVA revealed that there were no significant differences between treatment groups, P > or = 0.05. However, when the data were stratified into sites which retained or lost the ePTFE membrane, the percent of bone regeneration was reduced in group A. Therefore, it may be recommended that nonsubmerged implants be placed with a submerged or "semi-submerged" protocol when utilized in conjunction with ePTFE membranes.

Animals

Dental implant infections.

Dental implants provide a restorative tool to support crowns, bridge abutments, and removable dentures. Osseointegrated implants are titanium posts that are surgically implanted in alveolar bone. A tight immobile bond (osseointegration) forms between bone and titanium, and prosthetic and restorative fixtures are attached to the implants. Titanium implants differ from natural teeth, which may make them more susceptible to mechanical stress. A small proportion of implants are not successful and may fail due to infection. The microbiota of implants is similar to that of teeth in similar clinical states. Implants that fail because of mechanical stress are colonized by species associated with healthy teeth. Infected implants are colonized by subgingival species, including Porphyromonas gingivalis, Bacteroides forsythus, Fusobacterium nucleatum, Campylobacter gracilis, Streptococcus intermedius, and Peptostreptococcus micros. Different patients may be colonized by different microbial complexes, indicating that optimal treatment should be directed to the specific infection.

Bacterial Infections

Laser catheter coagulation of atrial myocardium for ablation of atrioventricular nodal reentrant tachycardia. First clinical experience.

A new technique for ablation of atrioventricular nodal reentrant tachycardia, using catheter-directed continuous wave Nd-YAG laser light, 1064 nm, via a novel pin-electrode laser catheter, was applied in 10 patients aged 15-63 years (mean 43 years). A total of 22 laser pulses, 1-5 per patient, at 20 or 30 W, of 10-45 s (mean 27 s) were aimed at the postero-inferior aspect of the tricuspid annulus. In all patients the tachycardia was rendered non-inducible at baseline as well as during orciprenaline administration. The amplitudes of the local atrial potentials diminished from 2.0 +/- 0.5 before to 0.4 +/- 0.4 mV after ablation, atrio-His intervals increased from 73 +/- 7 to 157 +/- 36 ms. Anterograde atrioventricular nodal refractory periods (212 +/- 31 vs 238 +/- 31 ms) and Wenckebach rate (174 +/- 8 vs 167 +/- 8 beats.min-1) did not change significantly (P > 0.05). There were no complications or recurrent arrhythmias in a follow-up of 12-35 (mean 27) months. Anatomically guided laser catheter coagulation of the postero-inferior aspect of the tricuspid valve ring is a safe and effective method for the cure of patients with common atrioventricular reentrant tachycardia.

Adult

The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients.

OBJECTIVES: To further define the clinical spectrum of the disease for pediatric and metabolic specialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde dehydrogenase (SSADH) deficiency in the differential diagnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative organic acid analysis in such patients. PATIENTS: The clinical features of 23 patients (20 families) with SSADH deficiency (4-hydroxybutyric acid-uria) are presented. The age at diagnosis ranged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families. OUTCOME MEASUREMENTS: The following abnormalities were observed (frequency in 23 patients): motor delay, including fine-motor skills, 78%; language delay, 78%; hypotonia, 74%; mental delay, 74%; seizures, 48%; decreased or absent reflexes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; neonatal problems, 26%; and electroencephalographic abnormalities, 26%. Associated findings included psychoses, cranial magnetic resonance or computed tomographic abnormalities, and ocular problems in 22% or less of patients. Therapy with vigabatrin proved beneficial to varying degrees in 35% of the patients. Normal early development was noted in 30% of patients. CONCLUSIONS: Our data imply that two groups of patients with SSADH deficiency exist, differentiated by the course of early development. Our recommendation would be that accurate, quantitative organic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, motor, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis can be confirmed by determination of enzyme activity in white cells from whole blood. We think that increased use of organic acid determination will lead to increased diagnosis of SSADH deficiency and a more accurate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metabolic and clinical profiles of SSADH deficiency.

Adolescent

Clinical trials on placement of implants in existing bone.

The use of dental implants has become a predictable and frequently used treatment modality in partially and fully edentulous patients. In 1987, the United States Food and Drug Administration (FDA) classified dental implants as class III medical devices. In 1989, a proposed rule was published by the FDA calling for a Premarket Approval Application (PMA) for dental implants. A PMA requires the demonstration of safety and effectiveness through clinical trials. Although the effective date for Premarket Approvals and detailed information on study requirements have not been announced, many implant manufacturers have already initiated multi-center clinical trials. Despite these initiatives, several aspects regarding appropriate study designs, outcome criteria, and success or failure analysis still need clarification. Trials should be designed to minimize bias and variability. The cornerstone of the experimental design is set by the study objective. It will determine which of many possible clinical trial parameters are essential to enable the presentation of data to a regulatory body on which basis the safety and effectiveness of a device can be judged. With the multiplicity of patient characteristics, implant types, supported prostheses, study designs, evaluation parameters, and statistical analyses, it is a difficult task to design an optimal trial. It is the purpose of this paper to propose designs and components for implant clinical trials with various objectives.

Clinical Trials as Topic

Hard-tissue augmentation for the placement of anterior dental implants.

Dental implants have become a popular alternative for replacing missing teeth in every region of the oral cavity. In the anterior zone, special esthetic concerns require not only a stably anchored implant for long-term success, but also the presence of adequate hard and soft peri-implant tissues. Anterior tooth loss is often accompanied by considerable loss of alveolar bone, so augmenting hard tissue before or in combination with implant placement becomes a critical part of therapy. One of the most successful augmentation techniques is guided bone regeneration (GBR). Thus far, augmentation procedures using expanded polytetrafluoroethylene membranes (ePTFEa) have proved to be the most efficient and predictable surgical technique to enhance deficient bone sites. This article discusses some critical biological and clinical/technical aspects of GBR and describes techniques for anterior hard-tissue augmentation with the photographic documentations of three clinical cases.

Alveolar Bone Loss

Evaluation of ERCP- and endoscopic sphincterotomy-induced pancreatic damage: a prospective study on the time course and the significance of serum levels of pancreatic secretory enzymes.

In the present study the time courses of serum lipase, serum amylase and serum elastase 1 after ERCP/ES as indicators for pancreatic damage were prospectively analysed in 46 cases. The elevations of pancreatic enzymes after ERCP/ES scattered in a wide range and elevations occured which were greater than one hundred times the upper limit of normal. A moderate increment was seen as early as 5 minutes after intubation of the papilla. Elevations above the upper limit of normal were still seen at 24 hours after the procedure. The maxima occurred about 6 hours after the procedure. Lipase was the most sensitive among the parameters tested, nearly 50% of the cases with previously normal values revealed elevated lipase after the procedure. For daily clinical routine a single lipase measurement at 2 hours after the beginning of the ERCP/ES provides valuable information for planning further surveillance. Younger age and high calcium levels seem to be risk factors for ERCP/ES-induced pancreatic damage. The time course of serum lipase seems to be a more reliable criterion for ERCP/ES-induced pancreatic damage than the poorly defined complication of post-ERCP pancreatitis . The high incidence of a measurable pancreatic injury after ERCP/ES provides a sensitive tool for the testing of drugs claimed to be protective for the pancreas and for evaluating new ERCP/ES techniques. Measurement of the serum lipase before, 8 and 24 hours after the procedure, and a detailed description of degree and duration of pain, are necessary for such studies.

Adult

The 3D-structure of a natural inhibitor of cell adhesion molecule expression.

The three-dimensional structure of cyclopeptolide HUN-7293, a naturally-occurring inhibitor of cell adhesion molecule expression, has been determined from nuclear magnetic resonance data recorded in solution and from X-ray diffraction analysis of single crystals. The backbone conformation of HUN-7293 is characterized by two cis-peptide bonds in both the solution and crystalline state. Differences between the solution and crystal structure are visible for the orientation of some side chains and the strength of two transannular hydrogen bonds. Such structural information helps to provide insight into the molecular architecture of HUN-7293 on the atomic level and opens the way for structure-based modifications of this novel inhibitor of cell adhesion molecule expression.

Amino Acid Sequence

Temperature and pressure effects during erbium laser stapedotomy.

BACKGROUND AND OBJECTIVES: Laser-assisted stapedotomy has become a well-established alternative to the mechanical drilling method. The goal of this study is to quantify the mechanical and thermal tissue effects and to determine optimum erbium laser parameters for safe clinical treatment. STUDY DESIGN/MATERIALS AND METHODS: On an inner ear model, time-resolved pressure measurements and Schlieren optical flash photography were performed during the perforation of the stapes foot plate using an erbium laser at 2.79 microns. The laser radiation was transmitted via an optical zirconium fluoride fiber. The laser-treated foot plates were investigated by light microscopy and scanning electron microscopy to visualise the laser-induced tissue effects. RESULTS: Perforation of the stapes foot plate can be performed with a few erbium laser pulses with high precision and a thermal damage zone of < 10 microns. Strong pressure transients were found to be generated by the bone ablation process and the collapse of a vapor channel created in the perilymph after fenestration. CONCLUSION: From the comparison of the laser-induced pressure with the limit graph to avoid hearing defects published by Pfander, an unobjectionable use of the erbium laser is deduced for fluences < 10 J/cm2. The erbium laser seems to represent an ideal instrument for middle ear surgery with all the advantages (precision, fiber optic transportable, high ablation efficiency, safety) desired for clinical application.

Erbium