The rat myosin myr 5 is a GTPase-activating protein for Rho in vivo: essential role of arginine 1695.

myr 5 is an unconventional myosin (class IX) from rat that contains a Rho-family GTPase-activating protein (GAP) domain. Herein we addressed the specificity of the myr 5 GAP activity, the molecular mechanism by which GAPs activate GTP hydrolysis, the consequences of myr 5 overexpression in living cells, and its subcellular localization. The myr 5 GAP activity exhibits a high specificity for Rho. To achieve similar rates of GTPase activation for RhoA, Cdc42Hs, and Rac1, a 100-fold or 1000-fold higher concentration of recombinant myr 5 GAP domain was needed for Cdc42Hs or Rac1, respectively, as compared with RhoA. Cell lysates from Sf9 insect cells infected with recombinant baculovirus encoding myr 5 exhibited increased GAP activity for RhoA but not for Cdc42Hs or Rac1. Analysis of Rho-family GAP domain sequences for conserved arginine residues that might contribute to accelerate GTP hydrolysis revealed a single conserved arginine residue. Mutation of the corresponding arginine residue in the myr 5 GAP domain to a methionine (M1695) virtually abolished Rho-GAP activity. Expression of myr 5 in Sf9 insect cells induced the formation of numerous long thin processes containing occasional varicosities. Such morphological changes were dependent on the myr 5 Rho-GAP activity, because they were induced by expression the myr 5 tail or just the myr 5 Rho-GAP domain but not by expressing the myr 5 myosin domain. Expression of myr 5 in mammalian normal rat kidney (NRK) or HtTA-1 HeLa cells induced a loss of actin stress fibers and focal contacts with concomitant morphological changes and rounding up of the cells. Similar morphological changes were observed in HtTA-1 HeLa cells expressing just the myr 5 Rho-GAP domain but not in cells expressing myr 5 M1695. These morphological changes induced by myr 5 were inhibited by coexpression of RhoV14, which is defective in GTP hydrolysis, but not by RhoI117. myr 5 was localized in dynamic regions of the cell periphery, in the perinuclear region in the Golgi area, along stress fibers, and in the cytosol. These results demonstrate that myr 5 has in vitro and in vivo Rho-GAP activity. No evidence for a Rho effector function of the myr 5 myosin domain was obtained.

[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.

Cytotoxicity of phenol to musculoskeletal tumours.

Local treatment with phenol is often used after intralesional excision of chondroblastomas and giant-cell tumours which involve bone near joints, and has been shown to reduce the rate of recurrence. The ideal concentration of phenol is uncertain, but may be important because of the high rate of absorption and toxicity. We have studied the effectiveness of different concentrations on standard sarcoma cell lines. Our results suggest that a 5% solution of phenol is effective against dispersed single cells, and that higher concentrations give no significant advantage, but create problems due to lack of homogeneous mixing, temperature and safety.

Magnesium treatment of torsade de pointes--a case report.

An eighty-one-year-old woman received quinidine in order to convert atrial fibrillation to a sinus rhythm. The patient developed a prolonged QT interval on the EKG, as well as episodes of torsade de pointes. With the administration of intravenous magnesium sulfate, the abnormal rhythm was suppressed within minutes. Thus, magnesium should be the first drug used in patients with torsade de pointes and prolonged QT interval on the electrocardiogram.

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.

The intergenerational transmission of corporal punishment: a comparison of social learning and temperament models.

This family study examined two models regarding the intergenerational transmission of corporal punishment. The model based on social learning assumptions asserted that corporal punishment influences aggressive child behavior. The model based on temperament theory suggested that aggressive child behavior impacts upon parental use of corporal punishment. Participants were 1,536 parents of 983 college students. Corporal punishment was assessed from father, mother, and child perspectives. Path analyses revealed that the social learning model was most consistent with the data.

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.

Child provocativeness and gender as factors contributing to the blaming of victims of physical child abuse.

This study was an investigation of factors contributing to blame attributions directed toward victims of physical child abuse. The total sample consisted of 897 college undergraduates. Subjects read eight vignettes describing physically abusive parent-child interactions, and indicated their attributions of responsibility toward parent and child. We predicted that: (a) aggressively provocative children (compared to nonprovocative) would be ascribed greater blame; (b) male subjects would be more likely to blame the child; (c) in situations in which the abusive parent is male (compared to female), the child would be blamed more; and (d) male children (compared to females) would receive greater blame. The results supported all hypotheses. The data also suggested several interaction effects. Significance tests were supplemented with effect size analyses.

[Management strategy in severe craniocerebral trauma in a general surgical department]. / Versorgungsstrategie beim schweren Schädel-Hirn-Trauma in der allgemeinchirurgischen Abteilung.

Emergency treatment of severe head injury combined with multiple trauma in most cases must be performed in regional hospitals and in general surgical units. Especially in acute intracranial hemorrhage (epidural hematoma) with the urgent indication to craniotomy the transmission of the patient in a special neurosurgical department is not possible in an adequate time. Therefore general surgeons should be trained in emergency trepanation of the skull and in basic treatment of severe head injury including measuring of intracranial pressure. The tactics of treatment of severe cranio-cerebral trauma is demonstrated on 46 cases out of 869 patients with head injury treated in our hospital from 1981 to 1984.

Computer-based patient information. Legal basis, concept and 10 years' experience.

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.

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.

[Risk of hip endoprostheses in the aged--incidence of complications in patients over 70 years of age in a comparative study]. / Das Risiko der Hüftendoprothetik im Alter--Die Komplikationshäufigkeit bei über 70jährigen im Vergleich.

567 patients of more then 70 years old (average age 75 years) who underwent hip arthroplasty, were compared with a control group (average age 52 years). The incidence of risks differed in cardiovascular complications, fatality, confusional state and the occurrence of decubital ulcers. The differences were in the range of about 2%.

[Analysis and assurance of complete medical documentation]. / Analyse und Sicherung der ordnungsgemässen ärztlichen Dokumentation.

A written report on the findings of the examination forms the basis for the further procedure in the treatment of a patient--not merely in the area of orthopaedics. The examination findings should, therefore, be legible, readily understandable and complete. On the basis of 600 individual findings established at admission in the case of inpatients with diseases of the spine and hip, stemming from a total of three hospitals, the behaviour pattern of the individual examiner is analysed along with deficiencies in documentation. For a number of significant deficits, differences in the particular emphasis applied by individual physicians during the examination, the fact that the time available for such examinations is usually limited, and the lack of documentation system, are probably responsible.

[Bone transplantation and AIDS]. / Knochentransplantation und AIDS.

The necessary obligation to carefulness at homogeneous transplantation of bone in concern of the AIDS epidemiology are being presented. According to the actual state of the HIV epidemiology a single examination of femur head donors contains an almost unmeasurable small risk of a virus transmission. Prior condition to an examination of the donor and to the usability of bones is the informed consent of the donor. Also important is the education of the recipient about the remaining risk, a provable documentation and a continuous observation of the HIV epidemiology.

[Spondylitis in the aged]. / Die Spondylitis im Alter.

The spondylitis of the old patient is often late recognizable because of superposition with senile degeneration. The treatment is conform to the classical rules of musculoskeletal infections, after securing the diagnosis. The high risk of immobilisation in the age can be reduced by the operative therapy, but on the other hand must be an acceptance of the operative risk. Last named is very small, if the team is good acquainted with his work, accordingly short length of operation-time and without big histological lesions.

[Periarthropathia humeroscapularis]. / Periarthropathia humeroscapularis.

Degeneration of the rotator cuff causes the painful periarthritis humeroscapularis. Especially the supraspinatus tendon is afflicted. 90-95% of patients with acute affection of supraspinatus tendon get free from symptoms with conservative treatment. Impingement syndrome of the rotator cuff will also get free from symptoms with conservative treatment. When the symptoms persist in spite of treatment, the operative enlargement of the acromiocoracoidal passage is indicated. Periarticular soft tissue calcification often becomes painful during spontaneous absorption of calcium deposits. Conservative treatment is in the foreground.

[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.