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Biomedical subjects

U Meyer

Publications and source records attributed to U Meyer.

At least 91 records · Page 5Linked to original sources

Use of a mandibular fracture score to predict the development of complications.

PURPOSE: Mandibular fractures are common facial injuries. Classifications are diverse and sometimes correlated with specific treatment modalities. Osteosynthesis using plate and screws is the standard method of fracture treatment. To evaluate the outcome of such fracture management in our clinic, we developed a numeric scoring system for mandibular fractures and investigated the relationship between the scoring of the fracture being treated and the incidence of complications after surgical treatment. PATIENTS AND METHODS: Seventy-six adult patients treated over a 2-year period were evaluated, and the fractures were classified using the mandibular trauma score. This score was based on clinical and radiologic evaluation of each fracture line and ranks from 0 to 15 points. Osteosynthesis was performed using the AO plate systems. Patients were followed-up postoperatively for the presence of complications. RESULTS: During the 2-year period, 76 patients with 134 fractures underwent plate osteosynthesis. Fracture scoring indicated a homogeneous distribution between uncomplicated and severe fractures. The incidence of complications increased with the fracture severity, assessed by the fracture score index. Severe fractures showed fewer complications when treated with a rigid plate system, whereas low-score fractures showed better results when treated with less rigid systems. CONCLUSIONS: The numeric scoring system for mandibular fractures allows an objective and standardized assessment of the degree of severity of a fracture and may facilitate decisions about the use of specific treatment modalities.

Adult↗

The effect of magnitude and frequency of interfragmentary strain on the tissue response to distraction osteogenesis.

PURPOSE: Bone regeneration is believed to be partially controlled by the applied local mechanical strain. To test whether the magnitude or frequency of discontinuous traction regulates the tissue response, defined daily strains were applied on mandibular osteotomies using an implanted mechanical distractor. MATERIALS AND METHODS: Unilateral mandibular osteotomies were performed in skeletally immature rabbits (n = 36). and distraction was done by applying 2,000, 20,000, 200,000, or 300,000 microstrains once or 10 times (2,000, 20,000 microstrains) per day, respectively. Sham-operated animals (n = 6), serving as controls, underwent frame application and osteotomy without distraction. At the end of the distraction process, the newly formed tissue was evaluated histomorphometrically by the use of a well-defined scoring system of bone-forming indices. RESULTS: The highest bone-forming indices were detected in the osteotomized, nondistracted group and in samples exposed to a physiologic strain (2,000 microstrains). Application of hyperphysiologic strains (200,000 and 300,000 microstrains) resulted in the formation of fibrous tissue and decreased bone-forming indices. Using Kruskal-Wallis tests, a statistically significant relationship was found between the bone-forming indices and the applied strain magnitudes. Scanning and transmission electron microscopic examinations showed osteoblastic differentiation and early mineral deposition in samples distracted up to 20,000 microstrains, whereas higher strain magnitudes led to the formation of fibroblast-like cells surrounded by collagen fibrils and only slight mineralization. Multiple strain applications (10 cycles/d vs 1 cycle/d) did not alter the histomorphometric indices or ultrastructural morphology significantly but increased the amount of newly formed tissue. CONCLUSIONS: These results suggest that the magnitude and not the frequency of mechanical loading controls the differentiation of bone cells and the subsequent formation of bone tissue.

Analysis of Variance↗

Decreased expression of osteocalcin and osteonectin in relation to high strains and decreased mineralization in mandibular distraction osteogenesis.

In a rabbit model of mandibular distraction osteogenesis, high strains resulted in a substantial reduction in the expression rate of the two osteogenic marker proteins, osteocalcin and osteonectin. In non-distracted samples and mandibles exposed to 2000 microstrains, staining for osteocalcin in the osteotomized area was detected in osteoblasts and diffusely dispersed in the mineralized matrix of the surrounding bone. However, in osteotomized mandibles distracted at strains above physiological levels (200,000 and 300,000 mustrains, respectively) the majority of osteoblast-like cells failed to express immunodetectable amounts of osteocalcin. Similarly, in the extracellular matrix of the distraction area the expression of osteonectin decreased by applying higher strains. Ultrastructural analyses of mandibular samples exposed to hyperphysiological strains revealed that the reduced expression rate of osteocalcin and osteonectin was paralleled by a significant loss of crystal formation, suggesting a functional role of both proteins related to mechanical loading.

Animals↗

Strain-related bone remodeling in distraction osteogenesis of the mandible.

Distraction osteogenesis has become a mainstay in craniofacial surgery. However, there are several unresolved problems concerning the biology of bone regeneration. We investigated the biomechanical effects of mandibular lengthening in 32 rabbits on a cellular and histologic level. The mandible was subjected to a corticotomy, held in a neutral position for 4 days, and then lengthened at various strain rates and frequencies for 10 days. Radiographic, histologic, and electron microscopic examinations showed a strain-related bone regeneration. Application of physiologic strain rates (2000 microstrains or 0.2 percent) led to a bridging of the artificial fracture exhibiting woven ossification, whereas at 20,000 microstrains trabecular bone formation was demonstrated. In contrast, hyperphysiologic strain magnitudes (200,000 microstrains and 300,000 microstrains) showed a fibrous tissue formation. Multiple strain applications (10 cycles/day versus 1 cycle/day) increased the width of the distraction gap without changing the stage of bone regeneration. The gradual distraction of bone in physiologic magnitudes at higher frequencies seems to be desirable for a bony differentiation and may help to improve clinical applications.

Animals↗

Violence against caregivers in nursing homes. Expected, tolerated, and accepted.

Violence against caregivers is not a new phenomenon. Caregivers have experienced verbal and physical assaults from nursing home residents for many years. However, because much of the violence has been associated with demented or mentally ill residents, the word aggression was used in lieu of violence. This study found that the caregivers and nursing directors considered the assaults to be violence. The study suggests that such violence occurs frequently and is of concern to caregivers and nursing directors. The study also suggests that nursing homes may not have policies or procedures in place for preventing, monitoring, and controlling violence in their workplaces. In 1996, OSHA published violence prevention guidelines for health are facilities. These guidelines support OSHA's mandate that employees are entitled to a safe and healthy workplace (OSHA, 1996b). Although it is not possible to prevent all violence against caregivers in this unique setting, nursing home directors and administrators have a legal and moral responsibility to develop an action plan to minimize the violence and plan interventions for its effects. Violence against caregivers in nursing homes no longer can be thought of as expected, tolerated, and accepted. Quality of care and employee well-being depend on it.

Adult↗

Differential stress gene expression during the development of Neurospora crassa and other fungi.

Stress genes are differentially expressed during the development of Neurospora crassa and other fungi. Large amounts of constitutive heat shock protein 70 (HSC70) are found in dormant conidia of N. crassa, whereas little mRNA of the related glucose-regulated protein (grp78) is detected. It is, however, not generally clear whether heat shock protein or mRNA is preferentially stored in dormant spores. Germinating spores of N. crassa increase the level of grp mRNA. During this developmental stage, the induction of inducible heat shock protein (hsp) genes can be elicited by heat shock only at certain times after the beginning of germination. Exponential growth (proliferation) is paralleled by increased levels of HSCs. The stationary state is characterized by decreased levels of some HSCs and increased levels of others. Conidiation in N. crassa is accompanied by a strong enhancement of the synthesis and levels of HSCs but also of HSPs after heat shock. This increase may serve a need for additional rounds of replication, for the expression and transport of sporulation-specific proteins or for stabilization of macromolecules in the spores and their preservation for germination. The control mechanisms involved in the differential expression of hsc genes are currently not known.

Gene Expression Regulation, Fungal↗

[Prospective study of the pathology of radiation-induced mucositis].

One of the most severe early side effects of radiation in head and neck cancer patients is mucositis. Inflammation of the oral mucose may lead to an extreme subjective burden, restricting the patients' well-being and even leading to an interruption of radiotherapy. The aim of our prospective study was to investigate the pathological alterations of the oral mucosa during irradiation. Therefore, samples from head and neck cancer patients were taken before radiation and a 30-G and a 60-G radiation dose. Pathogenetic alterations were determined by immunohistochemical staining of various cell surface molecules known to be involved in the pathogenesis of inflammation. Staining was performed with antibodies against ICAM 1, VCAM 1, ELAM, 25F9, 27E10, and RM3-1. Our study demonstrates the expression rates of the various surface molecules during inflammation. Expression of RM3-1 and ICAM 1 showed a steep increase during the time of radiation, whereas expression of ELAM reached a low constant value. Therefore, we conclude that distinct cell surface molecules demonstrate a characteristic time-dependent expression during radiation. Better insight into the pathogenesis of radiation-induced mucositis may help to develop a pathological classification of mucositis and to improve therapeutic strategies.

Aged↗

Cloning of glucocorticoid receptor and mineralocorticoid receptor cDNA and gene expression in the central nervous system of the tree shrew (Tupaia belangeri).

The glucocorticoid (GR) and the mineralocorticoid (MR) receptor mediate corticosteroid actions in the mammalian brain. Here, we report the sequence and distribution of both receptor subtype mRNAs in the central nervous system of the tree shrew Tupaia belangeri, a non-rodent mammal, phylogenetically located between insectivores and primates. The specific glucocorticoid and mineralocorticoid receptor cDNAs were cloned, employing polymerase chain reaction (PCR) based methods. The GR cDNA and MR cDNA encode the 776-amino acid (aa) and 977-aa receptor, respectively. Comparisons of both GR and MR with corresponding cDNA-sequences of other species revealed the highest homology to the human equivalents (GR: 90%, MR: 89% nucleotide sequence identity of the coding regions). The localization of GR and MR mRNA in tree shrew brain was investigated by in situ hybridization using 35S-labeled riboprobes. The GR mRNA is widely distributed throughout all observed brain areas, with high signal intensities in the dentate gyrus, piriform cortex, cerebellum, anterior pituitary, subfornical organ and pineal gland. Whereas, moderate expression of GR mRNA was noted in region CA1 of the hippocampus, region CA3 displayed only low signal intensity. MR mRNA hybridization is mainly restricted to the strongly labeled hippocampal formation, but in contrast to the localization pattern found in rat, higher signal intensities are detected in field CA1 than in CA3. These data indicate that both GR and MR mRNAs are highly expressed in tree shrew brain with a species-specific expression pattern.

Amino Acid Sequence↗

Morphological investigations of the myocardium of cardiomyopathic hamsters during the postnatal development and experimental hypoxia. A quantitative ultrastructural study.

The hereditary cardiomyopathy of the Syrian hamster (strain BIO 8262) as a model of human cardiomyopathy was investigated during postnatal development using ultrastructural morphometric analysis. The aim of the study was to establish basic ultrastructural morphometric data of cardiomyocytes of this model during all stages of the disease in comparison to corresponding stages of normal development, and to compare the ultrastructural resistance of normal and myopathic myocardium against acute hypoxic stress. The postnatal development of this cardiomyopathy is characterized by focal myolytic lesions already in the first postnatal days, extended myofibrillic and mitochondrial damage developing after the 1st month, and features of hypertrophy, disarray of myofibrils, thickening, and clumping of z-lines after the 4th month. Morphometric parameters of myopathic cardiomyocytes differing from those of the control are diminished volume density of myofibrils by about 10% of the control values in middle age, slightly increased volume density of sarcoplasmic reticulum and t-tubules in the 1st months, significant increase of them after the 3rd month, and significant alterations of many mitochondrial parameters indicating degenerations (numeric density, volume density, average volume, volume density of cristae, and of destroyed areas, and ratio of surface to volume density of mitochondrial cristae). Acute isobaric hypoxia was applied to myopathic and healthy hamsters of corresponding age (at day 100). Evaluation of ultrastructural morphometric parameters of cardiomyocytes revealed that especially mitochondria were more affected by hypoxia in the myopathic animals. The average mitochondrial volume was significantly more increased in the myopathic condition, the ratio of surface to volume density of cristae significantly diminished. Our ultrastructural - morphometric study has shown, that morphometric parameters in general can be assigned to the stages of cardiomyopathy, and that the ultrastructural differences are best expressed about the 4th month.

Animals↗

Attachment kinetics, proliferation rates and vinculin assembly of bovine osteoblasts cultured on different pre-coated artificial substrates.

Primary bovine osteoblasts were used to study in-vitro effects of attachment on vinculin assembly in cells cultured on various artificial substrates. Materials coated with fibronectin and bovine serum albumin (BSA) as well as untreated materials (tissue culture polystyrene and Aclar foils) were chosen to investigate substrate-dependent proliferation during the first 3 days of culture. Proliferation was highest on fibronectin-coated substrates, followed by BSA-coated and untreated substrates. During the first 24 h of cultivation, cell attachment kinetics revealed no significant difference between the various substrates. After 24 h detachment rates obtained by calcium depletion with ethylenediaminetetraacetic acid were highest on uncoated materials, followed by BSA- and fibronectin-coated substrates. Phase contrast microscopy revealed typical osteoblast morphology after cell adhesion for 24 h. The dynamic attachment process was concomitant with the reassembly of vinculin into streak-like focal contacts clustered on the ventral side of cells. The kinetics of vinculin reassembly were independent of the underlying coating. Thus, fibronectin coating of artificial substrates increased the attachment strength and proliferation rate of osteoblasts. While the reassembly of vinculin in focal contacts seems to be a prerequisite of osteoblast attachment in vitro, it does not seem to have profound effects on the subsequent cell behaviour on artificial substrates.

Journal Article↗

Immunophenotypic and clinical features of T-cell receptor gammadelta+ T-lineage acute lymphoblastic leukaemia.

The immunophenotypic and clinical features of TCR-gammadelta+ T-lineage acute lymphoblastic leukaemia (T-ALL) were prospectively analysed in 52 children with membrane CD3+ T-ALL. We observed a relatively high incidence of TCR-gammadelta+ T-ALL (26/52 patients). Leukaemic blasts from 22 children demonstrated TCR-alphabeta positivity, and simultaneous expression of the TCR-beta and -delta chain was found in four children. Clinical and haematological features of TCR-alphabeta and gammadelta+ T-ALL did not differ significantly, except that haemoglobin levels were significantly lower in TCR-gammadelta+ cases. Event-free survival at 4 years was significantly better in TCR-gammadelta+ compared with TCR-alphabeta+ T-ALL, but expression of TCR molecules did not emerge as an independent prognostic factor in multivariate analysis.

Acute Disease↗

Neural interfaces for regenerated nerve stimulation and recording.

A class of implantable, regeneration-type neural interfaces (NI's) for mammalian peripheral nerve recording and stimulation were developed using different fabrication processes and integrating purposely designed components. A typical NI comprises three main components: 1) a microfabricated silicon die incorporating a microelectrode array on multiple through-holes, 2) a polymer guidance channel housing the die, and 3) a flexible flat cable connecting the die to an external electronic circuitry. The design and fabrication of the NI's were aimed at achieving long term, reliable implants by taking into careful account the biological, electrical, and mechanical requirements of the specific implant site. Different versions of the NI were fabricated and implanted between the severed ends of the sciatic nerve in a mammalian animal model (rabbit). Morphological and histological evidence showed that nerves regenerated through the NI's and electrophysiological results demonstrated the recovery of electrical functionality. Moreover, the NI's allowed stimulation of the regenerated nerve producing a visible leg/foot contraction. The NI's presented in this paper are being further improved in the authors' laboratories with the ultimate goal of allowing the control of nerve motor and sensory functions in future prosthetic devices.

Action Potentials↗

Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin.

A genetic polymorphism in the metabolism of the anticonvulsant drug S-mephenytoin has been attributed to defective CYP2C19 alleles. This genetic polymorphism displays large interracial differences with the poor metabolizer (PM) phenotype representing 2-5% of Caucasian and 13-23% of Oriental populations. In the present study, we identified two new mutations in CYP2C19 in a single Swiss Caucasian PM outlier (JOB 1) whose apparent genotype (CYP2C19*1/CYP2C19*2) did not agree with his PM phenotype. These mutations consisted of a single base pair mutation (G395A) in exon 3 resulting in an Arg132-->Gln coding change and a (G276C) mutation in exon 2 resulting in a coding change Glu92-->Asp. However, the G276C mutation and the G395A mutation resided on separate alleles. Genotyping tests of a family study of JOB1 showed that the exon 2 change occurred on the CYP2C19*2 allele, which also contained the known splice mutation in exon 5 (this variant is termed CYP2C19*2B to distinguish it from the original splice variant now termed CYP2C19*2A). The exon 3 mutation resided on a separate allele (termed CYP2C19*6). In all other respects this allele was identical to one of two wild-type alleles, CYP2C19*1B. The incidence of CYP2C19*6 in a European Caucasian population phenotyped for mephenytoin metabolism was 0/344 (99% confidence limits of 0 to 0.9%). Seven of 46 Caucasian CYP2C19*2 alleles were CYP2C19*2B(15%) and 85% were CYP2C19*2A. The Arg132Gln mutation was produced by site-directed mutatgenesis and the recombinant protein expressed in a bacterial cDNA expression system. Recombinant CYP2C19 6 had negligible catalytic activity toward S-mephenytoin compared with CYP2C19 1B, which is consistent with the conclusion that CYP2C19*6 represents a PM allele. Thus, the new CYP2C19*6 allele contributes to the PM phenotype in Caucasians.

Alleles↗

Anorexia nervosa and sudden death in childhood: clinical data and results obtained from quantitative neurohistological investigations of cortical neurons.

A crude rate of mortality of 5.9% has been quoted for Anorexia nervosa (AN) in recent studies. There are different causes of death ranging from suicide to sudden death. Autopsy data are extremely rare about brain alterations in deceased AN patients. Reported in this study is a female patient, aged 13.5 years, who died of acute AN. Quantitative neurohistological investigation post mortem was performed on her brain. Results were compared with data obtained from a girl of the same age with no contributory neuropsychiatric findings. In the cortex of the anorexia case beside typical pyramidal neurons, a slim neuron type with one extremely long basal dendritic field was found to occur more frequently than normal. In the neurons of the AN case, the ramification pattern of single basal dendritic fields was found to be reduced and changes in the spine morphology, as well as reduction in spine density, were observed. However, a simultaneous lengthening of the terminal dendrites of higher order gave some evidence for repair mechanisms and neuronal plasticity. The AN-specific implications of these findings are discussed. The conclusion is that all AN deaths should be reported together with descriptions of causes and cerebral alterations.

Adolescent↗

[Oral manifestations of acute leukemia].

It is well known that non-specific mucosal alterations can occur during diseases of the leukopoetic system. In most cases they are an early sign and therefore provide the opportunity for timely diagnosis of the disease. In this clinical study type and frequency of oral lesions, gingival and periodontal indices, and hematologic status were examined at the time of diagnosis of the different types of acute leukemia. The results showed a significant difference in the frequency of oral lesions between acute myelogenous and acute lymphoblastic forms, irrespective of age and sex of the patient. There was no correlation between type and frequency of lesions and hematologic status.

Adult↗

[Oral manifestations in patients with systemic lupus erythematosus].

Forty-six patients with systemic lupus erythematosus underwent thorough dental examination to determine the frequency and severity of oral lesions and periodontal diseases. According to clinical criteria, disease was classified as severe (n = 26) or less severe (n = 20). The overall rate of mucosal involvement in the studied patients was 48%-from 54% in patients with severe disease, 40% in those with less severe disease. Patients with severe disease were found to have a higher rate of tooth loss and an increased rate of gingival inflammation. The severity of periodontal lesions correlated with alterations in the immunoglobulin pattern, particularly with an increase in gamma-immunoglobulins. Thus it is suspected that complex immunodysregulation in combination with immunosuppressive therapy is responsible for the high rate of oral and periodontal lesions in patients with systemic lupus erythematosus.

Adult↗

Expression of intercellular adhesion molecule 1 (ICAM-1) in childhood acute lymphoblastic leukaemia: correlation with clinical features and outcome.

To investigate whether expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in childhood acute lymphoblastic leukaemia (ALL) has an impact on the biological behaviour of the disease, we evaluated 751 children of the ALL-BFM 90 trial with B-cell precursor- (n = 677) or T-cell-ALL (n = 74) for CD54 expression within immunological subgroups, its correlation to certain clinical features, and therapy outcome. The highest percentage of patients expressing CD54 was found in common- and pre-B-ALL (76.1% and 61.4%, respectively). There was intermediate expression in pre-pre-B-ALL (47.8%), and the lowest expression was detected in T-ALL (12.2%). A significant positive correlation could be demonstrated between low CD54 expression (< 20% stained blasts) and high peripheral leucocyte counts, central nervous system (CNS) involvement, and splenomegaly at the time of diagnosis (P < 0.01). In addition, CD54 expression was a favourable but not independent prognostic factor. Event-free survival estimate at 4.5 years was 86% for CD54+ patients (n = 463), compared with 78% for CD54- patients (n = 241) (P < 0.01). These findings demonstrate that CD54 expression has an impact on dissemination patterns and outcome of childhood ALL, and emphasizes the potential relevance of adhesion mechanisms in influencing clinical characteristics and prognosis of haematological malignancies.

Child↗