[Mega-prostheses in revision knee arthroplasty]. / Megaprothesen in der Knierevision.

BACKGROUND: Due to a predicted increase in primary total knee arthroplasty (TKA), revision TKA will gain importance over the following years. Because the average age of patients receiving a TKA is decreasing the possible need for multiple revisions might increase as well. Despite efforts to minimize bone and soft tissue damage, the resulting bone and soft-tissue loss increases with each revision and will make the use of megaprostheses indispensable in the future. COMPLICATIONS: The implantation of a mega-prosthesis must be carefully considered and planned, since mega-prostheses in particular are associated with an increased risk of infection and loosening. Mechanical complications, patient-specific problems and periprosthetic infections can be either the cause for or the result of revision surgery of a mega-prosthesis. In the case of a complication, only a salvage procedure, namely an arthrodesis, amputation or-if necessary-the installation of a permanent fistula is commonly recommended.

Bone turnover and mineral metabolism in adult patients with hypophosphatasia treated with asfotase alfa.

There is limited understanding of how asfotase alfa affects mineral metabolism and bone turnover in adults with pediatric-onset hypophosphatasia. This study showed that adults with hypophosphatasia treated with asfotase alfa experienced significant changes in biochemical markers of bone and mineral metabolism, possibly reflecting enhanced bone remodeling of previously osteomalacic bone. INTRODUCTION: Hypophosphatasia (HPP), due to a tissue nonspecific alkaline phosphatase (TNSALP) deficiency, can cause impaired bone mineralization and turnover. Although HPP may be treated with asfotase alfa, an enzyme replacement therapy, limited data are available on how treatment with asfotase alfa affects mineral metabolism and bone turnover in adults with HPP. METHODS: ALP substrates, bone turnover and mineral metabolism markers, and bone mineral density (BMD) data from EmPATHY, a single-center, observational study of adults (≥ 18 years) with pediatric-onset HPP treated with asfotase alfa (NCT03418389), were collected during routine clinical care and analyzed from baseline through 24 months of treatment. RESULTS: Data from 21 patients showed significantly increased ALP activity and reduced urine phosphoethanolamine (PEA)/creatinine (Cr) ratios after baseline through 24 months of asfotase alfa treatment. There were significant transient increases in parathyroid hormone 1-84 (PTH), osteocalcin, and procollagen type 1 N-propeptide (P1NP) levels at 3 and 6 months and in tartrate-resistant acid phosphatase 5b (TRAP5b) levels at 3 months, with a significant decrease in N-terminal telopeptide of type 1 collagen (NTX) levels at 24 months. Lumbar spine BMD T scores continuously increased during treatment. CONCLUSION: Significant changes in bone turnover and mineral metabolism markers after asfotase alfa treatment suggest that treatment-mediated mineralization may enable remodeling and bone turnover on previously unmineralized surfaces. Urine PEA/Cr ratios may be a useful parameter in monitoring treatment during routine care.

Bone mineral density and fracture risk in adult patients with hypophosphatasia.

In adult hypophosphatasia (HPP) patients, elevated lumbar spine dual X-ray absorptiometry (DXA) values are associated with markers of disease severity and disease-specific fracture risk while femoral bone mineral density (BMD), being largely unaffected by the disease severity, may still be useful to monitor other causes of increased fracture risk due to low BMD. INTRODUCTION: Hypophosphatasia (HPP) is a rare inherited metabolic disorder due to deficient activity of the tissue-nonspecific alkaline phosphatase (TNAP). Clinical manifestation in adult HPP patients is manifold including an increased risk for fractures, but data regarding clinical significance of DXA measurement and associations with fracture risk and disease severity is scarce. METHODS: Retrospective single-center analysis of DXA scans in patients with confirmed HPP (documented mutation, clinical symptoms, low alkaline phosphatase activity). Further data evaluation included disease-related fractures, laboratory results (alkaline phosphatase, pyridoxalphosphate, phosphoethanolamine), and medical history. RESULTS: Analysis included 110 patients (84 female, mean age of 46.2 years) of whom 37.3% (n = 41) were harboring two mutations. Average T-Score level at the lumbar spine was - 0.1 (SD 1.9), and mean total hip T-Score was - 1.07 (SD 0.15). Both lower ALP activity and higher substrate levels (pyridoxalphosphate and phosphoethanolamine) were significantly correlated with increased lumbar spine T-Score levels (p < 0.001) while BMD at the hip was not affected by indicators of disease severity. Increased lumbar spine BMD was significantly associated with an increased risk for HPP-related fractures, prevalent in 22 (20%) patients (p < 0.001) with 21 of them having biallelic mutations. CONCLUSION: BMD in adult HPP patients is not systematically reduced. Conversely, increased lumbar spine BMD appears to be associated with severely compromised mineralization and increased risk for HPP-related fractures while BMD at the hip appears unaffected by indicators of disease severity, suggesting suitability of this anatomic location for assessing and discerning disorders with increased fracture risk owing to reduced BMD like osteoporosis. TRIAL REGISTRATION NUMBER: German register for clinical studies (DRKS00014022) DATE OF REGISTRATION: 02/10/2018 - retrospectively registered.

Structural studies on bioactive compounds. 30. Crystal structure and molecular modeling studies on the Pneumocystis carinii dihydrofolate reductase cofactor complex with TAB, a highly selective antifolate.

The crystal structure of the ternary complex of NADPH, the potent antifolate [2, 4-diamino-5-¿3-[3-(2-acetyloxyethyl)-3-benzyltriazen-1-yl]-4 -chloroph enyl¿-6-ethylpyrimidine] (TAB, 1) and Pneumocystis carinii dihydrofolate reductase (pcDHFR), refined to 2.1 A resolution, reveals that TAB binds similar to the antifolates trimethoprim and methotrexate. These data also reveal multiple conformations for the binding geometry of TAB with two preferred orientations of the acetyloxy and benzyl groups that results from a 180 degrees rotation about the N2-N3 triazenyl bond. The methyl of the acetyloxy and benzyl ring of TAB probes large hydrophobic regions of the p-aminobenzoyl folate binding pocket of the active site, in particular the region near Phe69, which is unique to the pcDHFR sequence. These results confirm prior molecular modeling investigations of the binding of TAB to pcDHFR that identified four low-energy binding geometries, two involving rotations about the terminal N(2)-N(3) triazenyl linkage and two involving atropisomerism about the pivotal pyrimethamine-phenyl bond. The primary differences in the molecular dynamics (MD) models and those observed in this crystal complex result from small conformational changes in active-site residues on energy minimization. However, two MD models place the acetyloxy and benzyl ring groups in a region of the active site between the cofactor-binding region and the p-aminobenzoyl folate pocket; an orientation never observed in any DHFR crystal structure to date. These conformers interact with solvent near the enzyme surface and are probably not observed due to the loss of specific hydrogen bonds with the enzyme. The high species pcDHFR selectivity of TAB could be the result of ligand flexibility that enables multiple binding orientations at the enzyme active site. Further modification of the acetyloxy region of TAB could increase its potency and selectivity for pcDHFR.

Ligand-induced conformational changes in the crystal structures of Pneumocystis carinii dihydrofolate reductase complexes with folate and NADP+.

Structural data from two independent crystal forms (P212121 and P21) of the folate (FA) binary complex and from the ternary complex with the oxidized coenzyme, NADP+, and recombinant Pneumocystis carinii dihydrofolate reductase (pcDHFR) refined to an average of 2.15 A resolution, show the first evidence of ligand-induced conformational changes in the structure of pcDHFR. These data are also compared with the crystal structure of the ternary complex of methotrexate (MTX) with NADPH and pcDHFR in the monoclinic lattice with data to 2.5 A resolution. Comparison of the data for the FA binary complex of pcDHFR with those for the ternary structures reveals significant differences, with a >7 A movement of the loop region near residue 23 that results in a new "flap-open" position for the binary complex, and a "closed" position in the ternary complexes, similar to that reported for Escherichia coli (ec) DHFR complexes. In the orthorhombic lattice for the binary FA pcDHFR complex, there is also an unwinding of a short helical region near residue 47 that places hydrophobic residues Phe-46 and Phe-49 toward the outer surface, a conformation that is stabilized by intermolecular packing contacts. The pyrophosphate moiety of NADP+ in the ternary folate pcDHFR complexes shows significant differences in conformation compared with that observed in the MTX-NADPH-pcDHFR ternary complex. Additionally, comparison of the conformations among these four pcDHFR structures reveals evidence for subdomain movement that correlates with cofactor binding states. The larger binding site access in the new "flap-open" loop 23 conformation of the binary FA complex is consistent with the rapid release of cofactor from the product complex during catalysis as well as the more rapid release of substrate product from the binary complex as a result of the weaker contacts of the closed loop 23 conformation, compared to ecDHFR.

Relation between cranial base flexure and position of the jaws.

Correlation between the cranial base flexure with the sagital and vertical positions of both jaws has been analysed on 180 radiographs of eugnathic probands and 256 radiographs of patients with various malocclusion forms. Radiographs were analysed by conventional cephalometric procedures determining maxillar rotation, mandibular rotation, sagittal position of the maxilla, sagittal position of the mandible, and cranial base flexure. A significant correlation between the degree of cranial base flexure and facial prognathism was found. The correlation coefficients were higher in eugnathic probands than in those with malocclusions. Regression analysis defined three basic types of sagittal bimaxillar relations: orthognatism, retrognatism and prognatism.

The need to be more efficient: lessons learned from a department of nursing reorganization.

The Department of Nursing at General Leonard Wood Army Community Hospital, Fort Leonard Wood, Missouri, recently reorganized to improve efficiency. Evening, night, and weekend supervisors were eliminated and a new "crisis nurse" role was established. Excess inpatient resources were shifted to outpatient clinics. The process of planning and implementing the reorganization is described. Evaluation was accomplished by reviewing objective criteria as well as outcomes of crisis nurse and middle management seminars and a comprehensive staff survey. The reorganization did not appear to adversely affect quality of patient care, but lessons were learned regarding staff morale, departmental communication patterns, clarification of newly established roles, and participation of middle managers in planning and decision making.

[The gnathometric evaluation of the effect of bionator in the treatment of Class II Division 1 malocclusions]. / Gnatometrijsko vrednovanje ucinka u tretmanu anomalija Klase II/1.

Treatment of class II division 1 malocclusion has a very important place in orthodontics because of the high frequency of this group of anomalies, as well as its special effect upon the face. The functional jaw orthopedics is of a special importance with its wide choice of orthodontic devices of which the Balter's Bionator can be put apart. The objective of this study was to gnatometrically check the efficiency of Bionator in the treatment of class II/division 1 malocclusions. Ten patients of both sexes aged from 10 to 12 years were examined and diagnosed in accordance with the clinical criterion. The following are conclusions: After twelve month of treatment, class I sagittal occlusal relation was established in all the patients. The normal values of the sagittal incisal scale were established. Bionator has shown the largest influence upon the sagittal jaw relation, whereas the effects of the transversal dimension could be neglected. Because of its obvious positive effects, the Bionator I can be recommended as the best method in the treatment of class II/division 1 malocclusion.

[Application of computerized teleroentgenographic analysis in orthodontic diagnosis]. / Primjena kompjutorizirane telerendgenske analize u ortodontskoj dijagnostici.

The rapid advancement of electronics and availability of inexpensive personal computers have resulted in analytical programs for metric evaluation and graphic presentation of cranial roentgenograms and made it possible to predict craniofacial growth. Hence, an increasing number of roentgen-cephalometric analyses is now based on computerized data processing. The objective of this paper was to cast light on various aspects of computerized latero-lateral teleroentgenographic analysis by presenting recent literature data pertaining to this subject. The following conclusions have been reached: despite the fact that the number of data processed is very large, the time of processing is ten times shorter compared to conventional data processing; most analytical errors refer to the location of roentgen-cephalometric points; elaboration of orthodontic treatment on the basis of computerized growth prognosis is not recommended; despite its systemic limitations, there are numerous arguments in favor of the routine use of computerized roentgeno-cephalometric analysis.

[Changes in the value of the mandibular angle and its segments during growth]. / Promjene vrijednosti mandibularnoga kuta i njegovih segmenata tijekom rasta.

The mandibular angle, an important roentgenocephalometric parameter, undergoes marked changes during growth and development. The dynamics of alterations of the entire mandibular angle and its two segments was studied in a sample of 200 roentgenograms of eugnathic subjects divided into homologous age groups at 10-year scale intervals to the adult age. For each age group, three roentgenocephalometric variables were statistically processed. Results, presented numerically and graphically, led to a conclusion that the size of the mandibular angle and its superior segment decreased considerably in a defined period of time. A decrease in the values of all variables was clearly seen in both adolescence and postadolescence.

[Cephalometric analysis in individuals with Class II/2 malocclusions]. / Analiza rendgenkefalometrijskih varijabli u ispitanika s pokrovnim zagrizom.

Various orthodontic anomalies class II/2, classified into several experimental groups, and eugnathic occlusion serving as controls, were studied by roentgencephalometry. The objective of the study was to detect possible distinctions in the quantitative values of the chosen variables and to select those which discriminate the group of class II/2 orthodontic anomalies most significantly. Attempts were made to ascertain whether or not there were sex-related differences. The teleroentgenograma of 241 examines, aged 10 to 18 years, of both sexes, were analyzed. The experimental group consisted of 61 examinees class II/2 orthodontic anomalies. The control group consisted of 180 examinees with eugnathic occlusion. Latero-lateral skull roentgenograms were taken according to the rules of roentgencephalometry. Using acetate paper, the drawings of profile teleroentgenograms were elaborated and the reference points and lineas were entered. A total of 38 variables were analyzed, of which 10 were linear, 19 angular, 8 variables were obtained by mathematical calculations, and the age variable was also analyzed. For statistical analyses and electronic computer was used. The results are presented in tables and graphs. The results obtained have shown: that, when compared to the findings in the control group, the subjects in the experimental groups manifested significant changes in the following craniofacial characteristics: retroposition and retroinclination of the upper incisors; increased difference of the position of the apical basis of the jaw; marked convexity of the osseous profile; mandibular retrognathism and increased proportion of the maxillary compared to mandibular base; that, with regard to the sex of the examines, only linear variables of significantly discriminating character were selected. Thus it could be concluded that there were no significant sex differences among the morphological characteristics of the viscerocranium.

[A cephalometric analysis of cases with open bite]. / Analiza rendgenkefalometrijskih varijabli u ispitanika s otvorenim zagrizom.

A cephalometric study of 46 cases of both sexes, with open bite (experimental group), aged 10 to 18 years, was performed. The control group consisted of 180 cases with normal occlusion. A total, of 38 linear and angular variables were analyzed. Age variable as well as sex-related differences were also estimated. Compared with the control group, experimental group demonstrated significantly higher mean values for the following variables: lower segment of the mandibular angle, mandibular angle, basal angle, Bjork's polygon, mandibular anterior cranial base planes angle and Y-axis angle. The proportion between the facial hights was significantly decreased in the experimental group. In addition, retroclination of the lower incisors was significantly higher in the experimental than in the control group. Only four linear variables showed significant sex-differences. It may be concluded that there are no significant sex difference for most of morphological characteristics of the viscerocranium.

[Roentgencephalometric evaluation of inclination and the position of incisors in orthodontic malocclusions and normal occlusion]. / Rendgenkefalometrijska procjena odnosa inklinacije i pozicije sjekutica kod ortodontskih nepravilnosti i eugnate okluzije.

The aims of the study were: --to determine sagittal differences in the position and inclination of incisors in defined orthodontic anomalies as compared to eugnathic occlusion; --to assess the importance of variable interrelationships for the evaluation of incisor orientation; and --to describe the distribution of compatibility of all linear and angular assessments of incisor orientation studied in relation to both jaws, direction of deviation and type of malocclusion. A sample of 436 roentgenograms taken in subjects of both sexes aged 10-18 years (180 with eugnathic occlusion and 256 with orthodontic anomalies) were analyzed. Five dentoalveolar variables were observed. Use of the 3 degrees = 1 mm principle allowed the inclination and position of incisors to be compared. The following conclusions were reached: --as compared to eugnathic subjects, dentoalveolar variables were changed in defined orthodontic malocclusions with clear differentiation according to type of anomaly; --a significant relationship was found for most variables used to assess the position and inclination of incisors; --a complete compatibility between the position and inclination was recorded in 16.7% and 15.7% of cases in the maxilla and mandible, respectively; --compatibility between the inclination and position was highest in subjects with eugnathic occlusion; and --inclination and position of incisors may be mutually independent or even contradirectional in one and the same subject, necessitating separate analytical evaluation.

[Roentgen cephalometric analysis of linear variables in a sample with normal occlusion]. / Analiza linearnih rendgenkefalometrijskih varijabli izdvojenog uzorka eugnate populacije.

Eight linear variables have been analysed in a sample of 200 persons with normal occlusion. Selected variables define the cranial base, basal planes of both jaws, anterior face height, upper and lower segment of the anterior face height, posterior face height and mandibular height. Particular aim of this investigation was to establish the differences according to age and sex, to describe the correlations as well as to define the proportional relations among the selected linear variables. From the results obtained the following conclusions were drawn: All variables increased by growing up; the greatest increase was found in posterior face height, and the smallest in cranial base length, The highest correlation was found between variables defining both facial heights. Index defining proportion between posterior and anterior face height (65.4) showed a horizontal growth tendency in the population investigated.

[Cephalometric analysis in cases with Class III malocclusions]. / Analiza rendgenkefalometrijskih varijabli u ispitanika s anomalijama progenijskog kompleksa.

Various orthodontic class III anomalies, classified into several experimental groups, and eugnathic occlusions serving as controls were studied by roentgencephalometry. The objective of the study was to detect possible distinctions in the quantitative values of two variables chosen and to select the variables which most significantly discriminate the group of class III orthodontic anomalies. Attempts were made to ascertain whether or not there were sex-related differences. The teleroentgenograms of 269 examines, aged 10-18 years, of both sexes were analyzed. The experimental group consisted of 89 examinees class III orthodontic anomalies. The control group consisted of 180 examines with eugnathic occlusion. Latero-lateral skull roentgenograms were taken observing the rules of roentgenocephalometry. Using acetate paper, the drawings of profile teleroentgenograms were elaborated and the reference points and lines were entered. A total of 38 variables were analyzed, of which there were 10 linear, 19 angular, and 8 variables were obtained by mathematical calculation; the age variable was also analyzed. In statistical analyses an electronic computer was used. The results are presented in tables and graphs. The results obtained showed that: --compared to the findings in the control group, the subjects in the experimental group displayed significant changes in the following craniofacial characteristics a negative difference in the position of the apical base of the jaw, manifest concavity of the osseous profile and diminished convexity of the profile of soft parts, retroinclination of the lower incisors, mandibular prognathism, increased mandibular angle and increased mandibular proportion compared to maxillary and the anterior cranial base; --with regard to the sex of the examinees, only four linear variables of significantly discriminating character were selected, so that in can be concluded that there were no significant sex differences among the morphological characteristics of the viscerocranium.

[X-ray examinations in orthodontic diagnostics as a source of ionizing radiation]. / Rendgenske pretrage u ortodontskoj dijagnostici kao izvor ionizirajuceg zracenja.

Orthodontics increasingly depends on X-ray examinations in the therapy and diagnosis of dento-facial anomalies. In the choice of roentgenologic diagnostic methods attempts are made to select a method that provides maximum information with the least irradiation of the patient. Insufficient knowledge of the biological effects of ionizing radiation may result in undue precaution by the doctor or utter indifference. Therefore, literature data were analyzed to cast more light on the risks of ionizing radiation. The following conclusions have been reached: orthodontists are obligated to expose their patients to a minimal possible radiation; it is not possible to define the safety threshold of X-ray radiation because of unpredictable stochastic effects, although the incidence of damage due to the lowest doses is negligible; the doses of radiation due to orthodontic X-ray examinations are within the range of natural, environmental doses. However, because of their cumulative effects, they should not be underestimated; stomatologic X-ray examinations account for 8 to 25% of all X-ray examinations, yet their contribution to genetically significant doses is the smallest; since the effects of genetically significant doses have not been scientifically elucidated to a sufficient extent, X-ray radiation should be maximally reduced, modern roentgenologic techniques should be used and the safety instructions should be strictly followed; if all safety measures are adhered to, it is not necessary to impose limitations with regard to the performance of orthodontic X-ray examinations; it is important to obtain from the patient history of his previous X-ray examinations; a favorable relationship should exist between medically warranted needs and possible damages to the patient; standardization of orthodontic X-ray diagnosis will facilitate recording of relevant data and the calculation of radiation doses.