Peri-implant reactivity and osteoinductive potential of immobilized rhBMP-2 on titanium carriers.

Recombinant human BMP-2 (rhBMP-2) was immobilized non-covalently and covalently as a monolayer on plasma vapour deposited (PVD) porous commercially pure titanium surfaces in amounts of 5-8 µg cm(-2), providing a ca. 10-fold increase vs. previously reported values. Dissociation of the immobilized [125I]rhBMP-2 from the surface occurred in a two-phase exponential decay: a first rapid phase (ca. 15% of immobilized BMP-2) with a half-life of 1-2 days and a second slow sustained release phase (ca. 85% of immobilized BMP-2) with a half-life of 40-60 days. Dissociation rate constants of sustained release of k(-1)=1.3-1.9 x 10(-7)s(-1) were determined, allowing an estimation of the binding constants (K(A)) for the adsorbed rhBMP-2 monolayer, to be around 10(12) M(-1). The rhBMP-2-coated surfaces showed a high level of biological activity, as demonstrated by in vitro epifluorescence tests for alkaline phosphatase with MC3T3-E1 cells and in vivo experiments. In vivo osteoinductivity of rhBMP-2-coated implants was investigated in a gap-healing model in the trabecular bone of the distal femur condylus of sheep. Healing occurred without inflammation or capsule formation. The calculated concentration of released rhBMP-2 in the 1mm gap ranged from 20 to 98 nM--well above the half-maximal response concentration (K(0.5)) for inducing alkaline phosphatase in MC3T3-E1 cells. After 4, 9 and 12 weeks the bone density (BD) and bone-to-implant contact (BIC) of the explanted implants were assessed histomorphometrically. Implants with immobilized rhBMP-2 displayed a significant (2- to 4-fold) increase in BD and BIC values vs. negative controls after 4-9 weeks. Integration of implants by trabecular bone was achieved after 4 weeks, indicating a mean "gap-filling rate" of ∼250 µm week(-1). Integration of implants by cortical bone was observed after 9 weeks. Control implants without rhBMP-2 were not osseointegrated. This study demonstrates the feasibility of enhancing peri-implant osseointegration and gap bridging by immobilized rhBMP-2 on implant surfaces which may serve as a model for future clinical applications.

[Therapy of enchondroma in long bones]. / Die Therapie des Enchondroms im langen Röhrenknochen.

The treatment of enchondroma in long tubular bones has been the subject of controversial discussions for several years. Whereas secondary malignancy is very rare when the enchondroma is located in a hand, a position near to the trunk represents a high risk of transformation into a chondrosarcoma. For an enchondroma in long tubular bones, authors recommend a whole variety of approaches ranging from regular controls to radical en bloc resection. Between 1989 and 2001 we followed a concept of intralesional resection and cement filling. After an interval without recurrences, the cement was extracted and replaced by a spongiosaplasty. Of 16 patients 12.5% suffered from an intralesional fracture in the course of the treatment, and 25% complained of persistent pain and loss of function after surgery. These complications led us to change our concept. Though there were two cases of secondary transformation into chondrosarcoma G1, we now prefer to keep the patients under close clinical and radiological control without performing surgery.

In vitro and in vivo performance of Ti6Al4V implants with plasma-sprayed osteoconductive hydroxylapatite-bioinert titania bond coat "duplex" systems: an experimental study in sheep.

To evaluate the in vivo performance of "duplex" hydroxylapatite top coat/TiO(2) bond coat systems, cylindrical Ti6Al4V rods of 130 mm in length and 11-13 mm in diameter were coated by atmospheric plasma spray (APS) technique with both a standard hydroxylapatite (HAp) layer and a HAp+TiO(2) bond coat "duplex" layer. In this pilot study coated and uncoated rods serving as controls were implanted into the femur of sheep so that their distal ends were freely suspended in the medulla of the femur. After an observation time of six months it was found that bone apposition and bone ingrowth were considerably increased in the presence of a osteoconductive coating. In particular, in vivo spalling and delamination frequently observed with HAp coatings was virtually absent in duplex coatings owing to the strong adhesion of the bond coat to the HAp top coat that anchored the latter solidly to the metallic surface of the implant. Some tentative mechanisms leading to this improved coating adhesion will be discussed.

[Primary hip- and knee arthroplasty--comparison of the actual costs with the Australian diagnosis related groups (DRG)-]. / Primäre Endoprothetik am Hüft- und Kniegelenk--Vergleich der Ist-Kosten mit den australischen Diagnosis Related Groups (DRG)

AIM: With the introduction of the Australian DRG system in Germany the question arises which current procedures remain reasonable in cost. The present study compares the actual costs with the expected DRG reimbursement. PATIENTS AND METHODS: Prospective analysis of 23 patients with primary hip and 26 with knee arthroplasty was performed to identify all cost factors during the hospitalization period including all applied measures. Retrospective analysis was carried out of the additional costs of relevant concomitant diseases (liver transplantation, haemophilia). RESULTS: Expenses of 6231 euro; for hip and 6453 euro; for knee implants were covered by the DRG reimbursement. Although a special reimbursement was paid, the additional costs of the concomitant diseases resulted in a financial loss. CONCLUSION: To cover the current costs for patients free of complications, an enormous reduction of the length of stay is required. Otherwise complicated cases may result in a loss of quality or selection of patients. The present cost analysis outlines a guideline for an individual calculation and assessment of the necessary DRG reimbursement.

[Unusual course of sacrococcygeal chordoma]. / Ungewöhnlicher Verlauf eines sacrococcygealen Chordoms.

Observation of a sacrococcygeal chordoma with exceptional long survival of now 17 years after incomplete surgery with following additional resection and adjuvant radiotherapy. Local recurrence occurred after more than 10 years, metastases after 15 years.

[Effect of graduate education on complication rate and costs of hip prosthesis implantation]. / Einfluss der Weiterbildung auf Komplikationsdichte und Kosten einer Hüftendoprothese.

PURPOSE: We studied the effect of surgical experience with regard to complications and costs after 3290 primary total hip arthroplasties (diagnosis: osteoarthritis). METHODS: We retrospectively analysed duration of clinical treatment and anaesthesia, blood loss, number of banked blood and perioperative complications (fractures of the shaft and acetabulum, dislocations, peripheral nerve injuries, thrombosis of the deep veins, embolism and deep wound infections) related to the experience of the surgeon (junior surgeons in comparison to the consultant) after 3290 primary THA's from 1974 to 1997. Cost analysis was performed by measurement of time and material expenditure. RESULTS: 39.2% of all operations were performed by junior surgeons. This number emphasizes the realisation of the order of education in our clinic. Both groups showed just few differences in number of duration of clinical treatment, banked blood, nerve leasions and embolism. We found statistically not significant increased rates of fractures and dislocations in the THA's performed by an unexperienced surgeon, however the rates decreased the last 14 years. Significantly higher rates of deep wound infection at the beginning decreased in the last 9 years to the level of experienced surgeons. Due to longer operation times, we calculated higher expenses of DM 85 per case in the group of junior surgeons. CONCLUSIONS: Using an educational program, carried out with an experienced surgeon, there is nearly no additional risk for the patient regarding the complication rates in THA's. However, there are higher financial expenses that have to be calculated.

[Survival rate of a cement-free cup of titanium with laser structured surface]. / Uberlebensrate einer zementfreien Pfanne aus Reintitan mit laserstrukturierter Oberfläche.

PURPOSE: So far no clinical results concerning the survival rates of cementless pure titanium cups with laser-structured surfaces exist. This study was performed to evaluate our results for the Alphasegment acetabular component (Alphanorm). METHOD: Retrospective analysis of 50 cups in 45 patients was performed (operations performed between November 1995 and January 1998). The average age at the time of the implantation was 65.1 years. Dysplastic hips and revisions were excluded. The survival rate was calculated according to the Kaplan-Meier analysis with the end point defined as the revision surgery of the cup. RESULTS: The average follow-up period was 2.9 (0.6-4.0) years. Two patients (i.e., two implants) died during the observation period, none were lost for follow-up. Six of the cups had to be revised due to aseptic loosening. The survival rate at 3.2 years after implantation was 87%. None of the stems had to be revised. CONCLUSIONS: Further use of the cementless hemispherical pure titanium cup with laser-structured surface cannot be recommended. The observed prevalence of loosening for the Alphasegment acetabular components was higher than for other cups. Close follow-up of patients with this type of implant is necessary.

[Value of digital subtraction arthrography and radionuclide arthrography in determination of indications and planning of revision surgery in total hip replacement]. / Stellenwert der digitalen Subtraktionsarthrografie und Arthroszintigrafie in der Indikationsstellung und Planung der Hüft-TEP-Wechseloperation.

PURPOSE: Clinical and radiographic findings are of little value in the diagnosis of hip endoprothesis loosening. Refined contrast and radionuclide arthrographic techniques are more precise in predicting endoprothesis loosening. Here we compare both techniques with respect to the surgical result. MATERIAL AND METHODS: 68 patients with hip pain after various arthroplasty procedure were investigated by clinical examination, X-ray, DSAr and AS. Surgical proof was obtained in 73.5%. RESULTS: An acetabular component loosening was detected in 89% by DSAr and in 86% by AS with a specificity for both methods of 93%. The femoral component loosening was seen with a sensitivity of 89% by DSAr and 100% by AS, respectively. Specificity of DSAr in the femoral compartment was 94%, of AS 88%. CONCLUSIONS: DSAr and AS are useful tools in the diagnosis of hip endoprothesis loosening and in planning surgical treatment. Both methods are comparable concerning the acetabular component, whereas AS is more sensitive in detecting femoral stem loosening. Combination of both methods is not recommended for routine diagnosis.

HPV16 L1E7 chimeric virus-like particles induce specific HLA-restricted T cells in humans after in vitro vaccination.

Cervical cancer has been shown to be highly associated with human papillomavirus (HPV) infection. The viral oncogenes E6 and E7 are constantly expressed by the tumor cells and are therefore targets for immunotherapy. In the present study we investigated the potential of HPV16 L1E7 chimeric virus-like particles (CVLP) to activate specific cytotoxic T lymphocytes in human blood donors. CVLP were expressed by recombinant baculovirus and purified. Direct incubation of freshly isolated peripheral blood lymphocytes (PBL) with CVLP resulted in induction of proliferation and growth of T cell lines. To enhance antigen presentation we also loaded dendritic cells with CVLP and used them to activate naive T cells. Growing cell lines were mainly CD3 positive (>95%) with a predominant CD4-positive and a minor CD8-positive component. Analysis of Tcell specificity was carried out by an interferon-gamma ELISpot assay. Dendritic cells pseudoinfected with CVLP or pulsed with human leukocyte antigen (HLA)-A*0201-restricted peptide E7(11-20) or with a newly identified HPV16 peptide L1(323-331) were used as stimulator cells. T cells responsive to CVLP were found in the cultures with frequencies of 0.5%-0.7%. Frequencies to peptides were around 0.1%. These T cells had cytolytic activity toward autologous B-lymphoblastic cell lines either pseudoinfected with CVLP or pulsed with HLA-A*0201-restricted peptides. They also lysed the HPV16- and HLA-A*0201-positive cervical cancer cell line CaSki, whereas HLA-A*0201-negative SiHa cells were not lysed. We conclude from our data that CVLP show promise for a therapeutic vaccine in patients with HPV16-positive cervical intraepithelial neoplasia lesions or cervical cancer.

[Cost analysis of hip and knee prostheses as the basis for cost-benefit evaluation]. / Kostenanalyse von Hüft- und Knieprothesen als Grundlage einer Kosten-Nutzen-Bilanz.

INTRODUCTION: The diagnosis-related reimbursement for total hip- and knee arthroplasty is often interpreted as a claim for cost reduction and thus influences increasingly the surgeon's choice of treatment. With regard to further planned budget reductions the following questions arise: Remains quality payable? Where are cost savings possible? PATIENTS AND METHODS: Prospective analysis of 21 patients with primary hip- and 26 with knee arthroplasties to identify all cost factors during the hospitalization period including the implantation technique and quality improvement measures. RESULTS: Expenses of 18,763.26 DM for hip- and 18,649.40 DM for knee implants were covered by the diagnosis-related reimbursement. Compared to cemented implants, the average total costs of cementless prostheses were usually less expensive. CONCLUSION: Although the current costs are covered, a further reduction of the diagnosis-related reimbursement may result in a loss of quality. The present cost analysis outlines a guideline for an individual calculation and assessment of possible saving effects.

[Implant positioning in epiphysiolysis capitis femoris. Sequelae of poor outcome and consequences]. / Zur Implantatpositionierung bei der Epiphysiolysis capitis femoris. Folgen des schlechten Verlaufs und Konsequenzen.

Which consequences can be ascribed to the intraarticular position of devices in the operative treatment of a slipped capital femoral epiphysis? Which steps are to define as a standard of a careful procedure? The clinical and radiological results of five cases of a pin or nail penetration after the operative treatment of a slipped capital femoral epiphysis are described, a possible connection of casualties is investigated. The intraarticular position of devices in most cases goes along with an unfortunate clinical outcome and leads to a higher risk of developing chondrolysis. Because of the radiologic overprojection with the femoral head it is possible to oversee the malposition of the pin. Any operative treatment of a slipped capital femoral epiphysis requires a careful intraoperative X-ray examination combined with documentation. With this procedure the bad results of an intraarticular implant position must be ascribed to the reminding risk of a fateful development.

Social support, attachment, and psychopathology in high risk formerly maltreated adults.

OBJECTIVE: The aim of this study was to examine the relationships among social support, attachment security, and psychopathology in an adult sample of high risk abuse survivors. Attachment security was conceptualized in terms of two underlying dimensions, the working models of self and other. METHOD: Sixty-six participants (24 men and 42 women) who met conditions for physical or sexual abuse were recruited from the greater Boston area. They completed the "Record of Maltreatment Experiences." the "Relationship Scales Questionnaire," the "Norbeck Social Support Questionnaire," and multiple measures of psychopathology. RESULTS: When multiple risk and protective factors were examined concurrently (e.g., social support, attachment, abuse history, IQ, SES), a negative view of self (one of the attachment poles) was the strongest predictor of overall psychopathology. Social support did not emerge as a significant direct predictor of psychopathology, once the effects of negative view of self were accounted for. However, among participants low on social support, in comparison to those who are high, a negative view of self was more highly correlated with some psychopathology measures. CONCLUSIONS: These findings indicate that among maltreatment survivors, negative view of self emerges as the most substantial predictor of psychopathology when examined in combination with other relevant risk factors.

Relationship between attachment style and posttraumatic stress symptomatology among adults who report the experience of childhood abuse.

This study examines the relationship between adult attachment style and posttraumatic stress symptomatology in a volunteer sample of adults who reported the experience of childhood abuse. Sixty-six individuals completed measures of abuse history, attachment style, and posttraumatic stress symptomatology. Results indicated that 76% of participants endorsed one of the three insecure attachment styles (dismissing, fearful, or preoccupied). Analyses of variances revealed that those who displayed fearful and preoccupied attachment styles, which represent a negative view of the self, had the highest mean scores on posttraumatic symptoms. Correlational analyses revealed a significant positive relationship between negative view of self and posttraumatic stress symptomatology, but not between negative view of other and posttraumatic stress symptomatology. Regression analyses indicated that having a negative view of self was most highly associated with posttraumatic stress symptoms, followed by a history of physical abuse. The regression analysis further indicated that negative view of other was unrelated to posttraumatic stress symptoms.

Social support and the relationship between family and community violence exposure and psychopathology among high risk adolescents.

OBJECTIVE: The objective of this study was to examine the protective effect of social support in the relationship between exposure to violence and psychopathology. Exposure to violence in the family and exposure to violence in the community were examined separately. Exposure to violence was further divided according to whether violence was experienced as a victim or as a witness. Internalizing and externalizing forms of psychopathology, as well as post-traumatic stress symptomatology were examined. METHOD: Participants consisted of 65 high-risk adolescents admitted consecutively to psychiatric inpatient units. Data were collected by means of individual interviews, self-report questionnaires, and hospital charts. RESULTS: Social support emerged as a protective factor with respect to the maladaptive effects of family violence, experienced as either a victim or as a witness. In contrast, social support did not appear to buffer the maladaptive effects of community violence, regardless of whether violence was experienced as a victim or as a witness. In fact, the relationship between community violence and psychopathology was found to be generally nonsignificant regardless of social support status. CONCLUSIONS: These findings suggest that exposure to family violence may affect development differently than exposure to community violence, allowing social support to effectively buffer the effects of family, but not community violence. This finding highlights the importance of examining violence exposure that occurs within the family separately from violence exposure that occurs within the community.

[Complete dislocation of the polyethylene inlay after internal hemipelvectomy and individually fitted tumor endoprosthesis]. / Komplette Luxation des PE-Inlays nach innerer Hemipelvektomie und individueller Tumorendoprothese.

We report about an exceptional complication after internal hemipelvectomy and replacement of the defect with a custom-made endoprosthesis. A complete luxation of the PE-inlay out of the metal cup occurred. Radiologically we assumed a luxation of the femoral head in dorsal direction. Revision after a failed attempt of closed reposition showed a complete luxation of the inlay, which was caused by deficient fixation in the acetabular component. The absence of a contrast wire in the PE-inlay delayed the right diagnosis and made it difficult to find the dislocated inlay in the large wound.

[Early loosening of a cemented hip endoprosthesis stem of titanium]. / Frühlockerungen eines zementierten Hüftendoprothesenstiels aus Titan.

Up to now there are no facts concerning the loosening rate of the cemented titanium stem (Trios). The central guiding canula and the longitudinal drilled stem shall ensure a symmetric cement mantle. In order to estimate the risk of aseptic loosening all Trios prostheses implanted in our clinic (n = 67; operations 1/95-11/96; max. follow-up: 3.1 years) were examined in a retrospective study and compared with a conventional femoral component (n = 141; Müller special; CoCr; operations 1977-1982). We used survivorship analysis to assess the results (Kaplan-Meier method; end point: revision). Compared to the conventional femoral stem the survival rate of the Trios prostheses was significantly worse (p = 0.0001). The probability of no revision after 3 years was 72% (conventional femoral component: 96%). Preoperative x-rays showed radiolucent lines surrounding the cement mantle. These findings as well as the loosening at the cement metal interface were confirmed intraoperatively. The explanted stems showed corresponding signs of abrasion on the surface. Our results prove that the application of cemented titanium stems might be problematic. With regard to the Trios prosthesis we recommend close routine check-ups to keep the chance of an early revision.

Shear strength of the cement metal interface--an experimental study.

The shear strength of the cement-metal interface using rods with different surface treatments and a clinical standardized cementing technique was studied. Under "dry" conditions, a low interface shear strength can be obtained with polished and smooth CoCrMo surfaces (peak-to-valley height Rt: 1 microm, average 0.2 MPa; 5 microm, 0.38 MPa). Grit-blasted and polymethylmethacrylate (PMMA)-precoated surfaces achieved higher values (PMMA precoat: average 5.16 MPa; CoCrMo peak-to-valley height Rt: 20 microm, average 8.61 MPa: 60 microm, average 7.8 MPa). After immersion in physiological saline solution for 60 days, the PMMA-precoated rods kept their initial stability whereas all the other test rods had lost their stability completely. A microscopic analysis of cross-sections revealed gap formations at the cement-metal interface to varying degrees (1-16 microm). PMMA-precoated rods rarely showed any gap formation at all. The above-mentioned gap formation was seen independently of the porosity at the cement-metal interface and corresponds to the clinical and postmortem observed debonding of the interface.

[Nerve lesions after hip prosthesis implantation--fate or treatment error?]. / Nervenläsionen nach Hüftprothesenimplantation--Schicksal oder Behandlungsfehler?

INTRODUCTION: Nerve lesions after hip arthroplasty are common complications which may imply the reproach of a treatment mistake. Thus, the decisive question to the expert runs: fate or treatment mistake? METHODS: Retrospective analysis of all cases dealt with at the medical expert commission of the General Medical Council Nordrhein during 1977-1997 in respect of the damage mechanisms and expert judgments. RESULTS: As long as diagnosis and therapy were set on time, nerve lesions after hip arthroplasty due to extension, pressure or placement of the leg were evaluated as fateful (81%). Delayed treatment as well as incorrect operation technique, -indication, or inadequate documentation were judged as a treatment mistake (19%). CONCLUSION: Nerve lesions after hip arthroplasty cannot always be avoided and thus do not directly imply a treatment mistake. Immediate therapy and precise documentation are important to minimize the damage.

[Computer-based patient information. Legal bases, concept and 10-year experience]. / Computergestützte Patientenaufklärung. Rechtliche Grundlagen, Konzept und Erfahrungen über 10 Jahre.

Culpable deficits of the preoperative information cause a complete illegality of the whole medical intervention and lead to liability for any resulting damage. In cases of controversy it's the physician's due to prove the correct preoperative information. To reduce these liability-risks a computer based information system has been developed. With its help an working sheet is provided which is individually adjusted for the patient. Based upon this record the real preoperative information takes place. After the patient signed the record the physician keeps it at his disposal for proving the contents of the preoperative information. The conception's use over many years shows that overlooking essential aspects and misunderstanding can grossly be excluded for the patient and a high quality of information can be reached.