Biomedical subjects
Publications and source records attributed to H Siebert.
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BACKGROUND: Restrictions in the bone structure of the craniomandibular region caused by malformation, traumata or malignant tumours are currently of interest in reconstructive oral and maxillofacial surgery. Methods of autologous bone transplantation are well established for reconstruction of those defects. The reconstruction and remodeling of contour-shaping defects is more difficult due to atrophy and resorption of free-transplantable tissues. Artificially induced harmful effects have been reported on harvesting in the donor area. Further available methods of alloplastic reconstruction are computer-assisted design and manufacturing systems (CAD/CAM). The advantages of individual design and fabrication are obvious in the manufacturing of defect-specific implants. MATERIAL AND METHODS: In the present study the application of individual CAD-based reconstructed bioceramic implants made of Bioverit II was evaluated in the region of the facial skull. Clinical results, patient acceptance and the analysis of the postoperative observation period of 30 months are reviewed. RESULTS: Altogether 25 individual Bioverit ceramics were implanted in the facial region. All patients were satisfied with the aesthetic results of the implantations after primary surgery. Three patients developed a need for further correction during the observation period; one implant fracture was observed. CONCLUSION: Finally, it can be stated that the preoperative expenditures in time, experts, technology and fabrication of individual CAD/CAM planned and manufactured implants are justified by the following advantages: fixed volume, reduced operating time, lack of donor morbidity, easy subsequent treatment of the material and the aesthetic results achieved.
OBJECTIVE: Hand injuries are not life threatening but crucial in multiple trauma because of their long-term functional results. The goal of this systematic review was to derive recommendations for diagnostic and treatment procedures from a systematic review of the literature. METHODS: Articles on hand injuries in multiple trauma and articles on clinical trails for isolated hand injuries were systematically collected (MEDLINE, Cochrane, and hand searches) and classified into evidence levels (1 to 5 according to the Oxford system). RESULTS: The special management of hand injuries in multiple trauma requires accurate diagnostic procedures, differentiated therapy strategies, and adequate timing. Depending on type and extent of the injury, there are substantial differences for primary or secondary operative treatment. CONCLUSION: Hand injuries represent important lesions in multiple trauma. Due to the life-threatening situation they may be overlooked in the beginning of the treatment. Because of their long-term consequences for function and health-related quality of life, hand injuries require an early and accurate diagnosis and a differentiated treatment strategy.
We set out to clarify whether in hospitals with a large volume morbidity and mortality rates after total knee arthroplasty (TKA) can be improved, whether the effects are consistent, and whether minimum recommendable caseloads can be inferred. We conducted a systematic review using MEDLINE, EMBASE, CENTRAL, and CINAHL and performed a hand search without restrictions on language or publication types. We identified 1406 citations, of which 13 studies including 1,110,962 patients met our inclusion criteria. Of these, six studies explored the same administrative data source. Five studies enrolling 448,897 were eligible for quantitative analysis. All studies corresponded to evidence level 2b (prospective or retrospective cohort study with >80% follow-up). We found homogeneous results about hospital mortality. Between 2551 and 821 TKA must be performed by high-volume rather than by low-volume providers to prevent 1 extra death. Absolute event rates are notably small.
The introduction of the DRG system in Germany-optional since 1 January 2003 and mandatory for all hospitals as of 1 January 2004-has resulted in great uncertainty, particularly on the part of hospitals, since apprehension prevails that the diagnostic and therapeutic measures practiced in Germany will not be appropriately represented and remunerated by a DRG system. The G-DRG version 1.0 prepared within the framework of substitutive execution is largely identical to the Australian AR-DRG version 4.1. Adjustments that do justice to the realities of German treatment modalities were at most insignificant. It is therefore essential that stock be taken for each medical specialty to determine to what extent treatment procedures commonly followed in Germany are adequately reflected in this G-DRG system or whether adjustments are necessary to make allowances for German realities. To be able to provide qualified statements on the problems involved, scientific analysis of possible problems is necessary utilizing German data. Thus, we undertook an evaluation of how the special fields of orthopedics and accident surgery are represented in the G-DRG system. The resultant data form the basis for evidence of presumable deficits in the representation of orthopedic and accident surgery cases in the G-DRG system. The German Association for Trauma Surgery and the German Association for Orthopedics and Orthopedic Surgery have undertaken a DRG evaluation project together with the Organization of Directors for Accident Surgery (chairperson: Professor Dr. Mischkowsky, Kempten), the Organization of Directors for Orthopedics (chairperson: Professor Dr. Puhl, Ulm), the DRG Working Group of the German Association for Accident Surgery, and the Joint Commission of the Professional Association of German Surgeons and the German Association for Surgery in cooperation with the DRG Research Group of the University Clinic Muenster, the German Hospital Association, and the German Medical Association with the goal of examining the medical and economic homogeneity of the case groups. A total of 12,645 orthopedic and trauma surgery cases were collected from 23 clinics-11 university hospitals and 12 non-university hospitals-and assessed. On the basis of this database and when too few cases were evaluable also based on clinical considerations, 14 adjustment proposals were formulated and submitted on schedule on 31 March 2003 to the Institute for Hospital Remuneration. The results of the DRG evaluation project illustrated the problems involved in representing the exceedingly heterogeneous and complex activities of orthopedic and trauma surgery departments in a flat rate financing system that is not attuned to the realties of German treatment procedures. Version 1.0 of the G-DRG system is not sufficiently differentiated to represent the multifaceted diagnostic and therapeutic services provided by trauma surgery and orthopedic departments in Germany.
Wallerian degeneration of a peripheral nerve is mainly characterized by axon and myelin degradation and is paralleled by a massive invasion of peripheral macrophages into the nerve. These cells enter the nerve attracted by a cascade of chemokines and cytokines but require proteolytic and enzymatic factors which enables them to cross the blood-nerve barrier. Here we investigated whether alpha-naphthyl (alpha-NA) esterases -- which have been shown to be exclusively expressed in human monocytes -- play a role during Wallerian degeneration. These enzymes were blocked by the specific inhibitor bis(4-nitrophenyl)-phosphate (BNPP) in an established in vitro model of Wallerian degeneration. Sciatic nerve segments of mice were co-cultured with peritoneal macrophages and BNPP was added to the cultures in various concentrations and at different timepoints. The macrophage numbers and myelin density in the nerve segments and the myelin load of macrophages were evaluated. After BNPP treatment the macrophage number within the nerve was significantly diminished and the myelin load within the macrophages was decreased, resulting in elevated levels of preserved myelin within the nerves. These experiments clearly showed a double effect of the alphaNA esterase inhibitor BNPP on macrophages. First, it suggests a role for alphaNA esterases on the migratory potential of macrophages since their invasion into the nerves was diminished. Second, the reduced myelin uptake is due to the inhibition of phagocytic capacity of these cells by BNPP. The therapeutical use of this inhibitor for treatment of autoimmune diseases such as multiple sclerosis or Guillain-Barré syndrome remains to be investigated.
The present study investigated the fate of macrophages in peripheral nerves undergoing Wallerian degeneration, especially their disappearance from the injured nerves after phagocytosis of axonal and myelin debris. Wallerian degeneration was induced in adult male C57Bl/6 mice by transecting the right sciatic nerve. Five days after transection, the male sciatic nerves were transplanted into female recipient mice by placing them exactly parallel to the host sciatic nerves. Nerves of the female recipient mice were also transected to induce breakdown of the blood-nerve barrier in the host animal. Apoptosis was assessed by morphological, immunohistochemical (activated caspase-3), and molecular (DNA fragmentation) methods in transplanted, recipient, and in control nerves. A subpopulation of macrophages within the degenerating nerves died locally by apoptosis in each experiment. The fate of the male macrophages within the transplanted nerves and the host organism was investigated by in situ hybridization with a Y-chromosome-specific DNA probe (145SC5). In situ hybridization specifically stained cells within the transplanted male nerve. Y-chromosome-positive cells were detected not only inside the transplanted nerve, but also inside the female host nerve, the perineurial tissue, the local perineurial blood vessels, draining lymph nodes and the spleen of the female host, suggesting hematogenous as well as lymphatic elimination of macrophages from the injured nerve. These data indicate that local apoptosis and systemic elimination via circulation to the local lymph nodes and the spleen are involved in the disappearance of macrophages from the injured peripheral nervous system.
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Wallerian degeneration after peripheral nerve transection leads to the phagocytosis of degenerated myelin and axon components by macrophages. These phagocytes are recruited from the systemic circulation and Wallerian degeneration may therefore be used as a model for myelin removal by hematogenous macrophages, a feature that is also a hallmark of demyelinating diseases of the central and peripheral nervous system. The immunomodulator linomide has been shown to be effective in the treatment of experimental demyelinating diseases although the exact mode of its action is not yet defined. The present study investigated the effect of linomide on monocyte invasion and myelin phagocytosis after sciatic nerve transection. Linomide had a dual effect in Wallerian degeneration. Monocyte migration from the circulation to the damaged nervous system was significantly reduced. Additionally, the myelin phagocytic capacity of macrophages was impaired, finally resulting in a significant delay in the removal of myelin. The present experiments may provide an explanation for the effects of linomide during the course of demyelinating diseases of the nervous system.
Wallerian degeneration is characterized by breakdown of myelin and axons with subsequent macrophage infiltration and removal of the degenerating nerve components. Proteinases of the matrix metalloproteinase (MMP) family seem to play an important role in demyelinating processes, since some of their members have been shown to cleave myelin basic protein. In the present study we investigated the expression of MMP-2 and MMP-9 (gelatinases A and B) during myelin removal after peripheral nerve trauma. After transection of the sciatic nerve an upregulation of MMP-2 and MMP-9 with a first peak 12 h and a second peak 48 h after axotomy was observed by zymography. These peaks correlate with the breakdown of the blood-nerve barrier, the accumulation of granulocytes, and the invasion of macrophages into the damaged nerves, respectively. Furthermore, MMP-2 was found to be upregulated in the contralateral nontransected nerves. Immunocytochemistry for MMP-9 and in situ zymography identified MMP-reactive cells within the distal nerve stump. Chloracetate esterase staining was used to detect granulocytes, which accumulated at the transection site and were colocalized with the in situ zymography signal. Wallerian degeneration of the transected nerve could be delayed either by intraperitoneal injections of hydroxamate (Ro 31-9790), a nonspecific MMP inhibitor, or by local application of an MMP-9-specific antibody. Following these treatment strategies, a decreased number of invading macrophages was seen in the nerves associated with an increased amount of preserved myelin sheaths. These results suggest that the invasion of macrophages into a transected peripheral nerve is accompanied by an increased expression of MMPs, particularly MMP-9. Thus, MMPs may seem to play an important role in the breakdown of the blood-nerve barrier and subsequent cell recruitment from the systemic circulation into the damaged nerve.
Wallerian degeneration is one of the most elementary reactions of the nervous system after transection of axons, leading to the recruitment of mononuclear cells from the systemic circulation. However, the exact mechanisms regulating this cell invasion have not yet been clarified in detail. Chemokines and their receptors play a central role in leukocyte trafficking, in particular the chemokine MCP-1 has been strongly implicated in macrophage recruitment to the injured nervous system. The present study investigates the course of Wallerian degeneration after transection of the sciatic nerve in mice deficient in two chemokine receptors: CCR2, the main receptor for MCP-1, and CCR5, a marker for Th1 T lymphocytes but also present on macrophages. The number of invading macrophages was determined by immunocytochemistry for three typical macrophage antigens (F4/80, Mac-1, LFA-1). The chemokine receptor CCR2 was expressed by infiltrating cells in the transected nerve stumps. Macrophage invasion was significantly impaired in CCR2-knockout mice when compared with wildtype controls and CCR5-deficient mice. Subsequently, there was a corresponding decrease in myelin phagocytosis due to the reduced invasion of phagocytic macrophages. These data demonstrate the involvement of the chemokine receptor CCR2 in macrophage recruitment to the injured nervous system.
The role of TNF-alpha in the course of Wallerian degeneration of the sciatic nerve was studied in control and TNF-alpha deficient mice. In control animals, the characteristic phenomena of Wallerian degeneration such as axon and myelin degeneration as well as macrophage recruitment with subsequent myelin removal were observed. In TNF-alpha deficient mice, in contrast, macrophage recruitment into the degenerating nerves was impaired resulting in a delayed myelin removal. However, the myelin phagocytic capacity of macrophages was not affected as it could be demonstrated by a similar myelin load of control and TNF-alpha deficient macrophages. These data indicate that the main function of TNF-alpha during Wallerian degeneration is the induction of macrophage recruitment from the periphery without affecting myelin damage or phagocytosis.
BACKGROUND AND OBJECTIVE: The evaluation of the appropriateness of hospital admissions and hospital stays has become an increasingly important issue in Germany. Evaluations by the German Physicians Review Organizations (MDS, MDK) demonstrated the need for a standardized, valid and reliable assessment tool for inappropriate hospital use. Objective of this study was to test the reliability of a German adaptation of the "Appropriateness Evaluation Protocol" (AEP). PATIENTS AND METHODS: From the 2317 admissions to medical wards of a teaching hospital in Hessia in 1997 we randomly selected 52 patients to test the inter-rater-reliability (54% female, mean age = 66 years +/- 18). Another 49 patients were randomly selected to test the intra-rater-reliability of the AEP (53% female, mean age = 61 years +/- 20). We estimated general agreement, specific agreement and Kappa statistics for the agreement of the evaluation of hospital admissions and hospital days. 95% confidence intervals were reported. RESULTS: The German adaptation of the AEP showed an inter-rater-agreement of 92% (88-96%) for hospital admissions and 76% (73-80%) for hospital days. Correspondingly, we observed an intra-rater-agreement of 96% (88-100%) for hospital admissions and 93% (91-95%) for hospital days. The high agreement was independent of the length of hospital stay and independent of the proportion of inappropriate hospital days. CONCLUSION: A standard instrument for the assessment of the appropriateness of hospital care with known metric properties may be useful for quality management in hospitals and provide competitive advantages in a consolidating health care market. The AEP could be such an instrument.
During the past years, the assessment of the appropriateness of hospital utilization has become increasingly important in the German health care system. Previous evaluations by regional review organizations in several states demonstrated the need for a standardized, reliable, and valid instrument to evaluate the appropriateness of inpatient care. Objective of the study is to test the reliability of a German adaptation of the "Appropriateness Evaluation Protocol" (AEP). Among all 2672 admissions from the department of surgery of a regional medical center during one calendar year, 54 patients were randomly selected to evaluate the inter-rater reliability and 51 patients to test intra-rater reliability. Overall agreement, specific agreement and Kappa statistics were estimated for every hospital admissions and all consecutive hospital days. The German AEP showed an inter-rater agreement of 74% (62-86%) for hospital admissions (Kappa = 0.44) and 84% (79%-88%) for all hospital days (K = 0.55). Intra-rater reliability was 88% (79%-97%) for hospital admissions (K = 0.60) and 88% (85%-92%) for all hospital days (K = 0.70). The observed agreement is independent of length of hospital stay and proportion of appropriate days. A standardized instrument with known metric properties is essential for quality management in hospitals to prepare for an increasingly consolidating health care market in Germany. The German AEP is a reliable instrument, which will allow to identify inefficiencies in the management of surgical inpatients.
BACKGROUND AND PURPOSE: Since the availability of a German adaptation of the "appropriateness Evaluation Protocol" (AEP) for hospital utilization review, physicians and health care managers were concerned about a potential overestimation of the extent of inappropriate hospital use in a retrospective assessment. The objective was to assess the agreement of concurrent and retrospective assessment of inappropriate hospital use. METHODS: The appropriateness of 42 admissions to surgical wards in a teaching hospital was tested concurrent to the admission. In 25 hospitalized patients the appropriateness of hospital days was assessed. Results were compared with the retrospective testing of the same patients after three months. RESULTS: Agreement between concurrent and retrospective assessment within the same reviewer was 86% of admissions (95% CI = 75%-96%) and 96% of hospital days (88%-100%). Kappa showed values of 0.85 and 0.78, which can be described as excellent. A comparison of two different reviewers, one testing concurrently, the other retrospectively showed agreements of 86% and 90%. The proportion of inappropriate days was the same in both designs. CONCLUSIONS: The results refute prior concerns that a retrospective assessment of the appropriateness of hospital use is impossible because in a retrospective design important clinical information would remain unconsidered or clinical information not yet available at that time would be used for the evaluation. The possibility of an incorrect assessment due to a retrospective design is within the variability inherent to the instrument. Despite the strong agreement, the small sample of surgical patient limits the generalizability of results.
OBJECTIVES: The purpose of this prospective cohort study was to determine the extent and determinants of hospitalization in a population sample of older disabled people. DESIGN: A longitudinal cohort study. SETTING: Noninstitutionalized disabled people in the region of Augsburg, South Germany. PARTICIPANTS: The study population included 2427 persons, aged 60 years and older, who, between 1991 and 1993, applied for benefits from the statutory health insurance system provided to the most severely handicapped noninstitutionalized persons. MEASUREMENTS: Baseline variables were derived from a standardized medical examination. Information about hospitalization and mortality until June 30, 1996, was extracted from records of the pertinent health insurance plan. Rate ratios (RRs) of hospitalization were derived from a multivariable Poisson regression model corrected for the correlation of multiple hospitalizations for each person. RESULTS: The overall absolute hospitalization rate was 6.7 hospitalizations per 10 person-years at risk, with a mean length of stay per hospitalization of 19.2 days. Multivariable analysis showed an inverse association of age and hospitalization. Persons cared for primarily by their children had a lower rate of hospitalization (RR = 0.83) than persons relying mainly on professional home care. Medical causes of disability and dependency with respect to activities of daily living were unrelated to the hospitalization rate. A total of 1415 persons (58.3%) died during follow-up. The rate of hospitalization was twice as high among these subjects compared with others. The hospitalization rate increased rapidly during the last year of life, with a peak increase in the last 3 months. CONCLUSIONS: This study expands the current inadequate database on hospitalization in Europe. Further expansion is necessary for the efficient allocation of medical resources to older people, a group steadily increasing in numbers.
The prion protein (PrP(C)) is a copper-binding protein of unknown function that plays an important role in the etiology of transmissible spongiform encephalopathies. Using morphological techniques and synaptosomal fractionation methods, we show that PrP(C) is predominantly localized to synaptic membranes. Atomic absorption spectroscopy was used to identify PrP(C)-related changes in the synaptosomal copper concentration in transgenic mouse lines. The synaptic transmission in the presence of H(2)O(2), which is known to be decomposed to highly reactive hydroxyl radicals in the presence of iron or copper and to alter synaptic activity, was studied in these animals. The response of synaptic activity to H(2)O(2) was found to correlate with the amount of PrP(C) expression in the presynaptic neuron in cerebellar slice preparations from wild-type, Prnp(0/0), and PrP gene-reconstituted transgenic mice. Thus, our data gives strong evidence for the predominantly synaptic location of PrP(C), its involvement in the regulation of the presynaptic copper concentration, and synaptic activity in defined conditions.
This study was undertaken to examine whether unilateral injury to one optic nerve (ON) elicits a response in the microglia, neuroglia and ganglion cells of the retina and ON of the contralateral site as well. Bilateral activation of the transcription factor c-jun could be immunohistochemically detected in the ganglion cell layer 2 days after crush and later. Microglial cells were detected with the activation-specific antibodies MUC 102 and OX-42. They showed an immediate and clear pattern of activation within the contralateral ON and retina, although this response was less pronounced than in the directly lesioned site. Astrocytes and Müller cells showed a typical up-regulation of glial fibrillary acidic protein in the lesioned retina and only focal but virtually no generalized up-regulation in the contralateral eye. Ganglion cells whose axons had been crushed responded with vigorous axonal growth after 2 days in culture, in addition to exhibiting in situ reactions. However, ganglion cells of the contralateral retina responded with a moderate regeneration, too. Growth was less pronounced than in the crushed retina but significantly better than in retinas on untreated animals. The results suggest that unilateral lesion of the optic nerve elicits a defined response in the major cell types of the contralateral retinofugal system. The findings suggest that it is advisable to maintain caution in the use of the contralateral optic nerve and retina as a control in experiments dealing with cellular processes of de- and regeneration.