Analgesics and Sedatives in Critically Ill Newborns and Infants: The Impact on Long-Term Neurodevelopment.

Inadequate pain and/or stress management in preterm- and term-born infants has been associated with increased morbidity and even mortality. However, exposure to analgosedatives during early infancy may also be one of the risk factors for subsequent neurodevelopmental impairment, at least in animal studies. Because infants admitted to neonatal or pediatric intensive care units may receive high amounts of these drugs for prolonged periods of time and the majority of these infants nowadays survive to discharge, this is of major concern. A balanced approach that incorporates the assessment and quantification of both wanted effects as well as unwanted side effects is therefore needed. In this article, the optimal dose determination of commonly used analgosedative drugs as well as their potential long-term effects on the developing human brain and neuropsychological functioning are reviewed.

Atom probe tomography study of Mg-doped GaN layers.

Atom probe tomography studies on highly Mg-doped homoepitaxial GaN (0001) layers with concentrations of 5 × 10(19) cm(-3) and 1 × 10(20) cm(-3) were performed. Mg cluster formation was observed only in the higher doped sample whereas in the lower doped sample the Mg distribution was homogeneous. CL measurements have shown that the emission normally attributed to stacking faults was only present in the lower doped layers (with Mg concentration of ∼5 × 10(19) cm(-3) or less), but absent in the higher doped layer, where Mg clusters were detected. Mg clusters are proposed to produce a screening effect, thereby destroying the exciton binding on the SFs and thus rendering them optically inactive.

Protection of quality and innovation in radiation oncology: the prospective multicenter trial the German Society of Radiation Oncology (DEGRO-QUIRO study). Evaluation of time, attendance of medical staff, and resources during radiotherapy with IMRT.

BACKGROUND: A number of national and international societies published recommendations regarding the required equipment and manpower assumed to be necessary to treat a number of patients with radiotherapy. None of these recommendations were based on actual time measurements needed for specific radiotherapy procedures. The German Society of Radiation Oncology (DEGRO) was interested in substantiating these recommendations by prospective evaluations of all important core procedures of radiotherapy in the most frequent cancers treated by radiotherapy. The results of the examinations of radiotherapy with intensity-modulated radiation therapy (IMRT) in patients with different tumor entities are presented in this manuscript. PATIENTS, MATERIAL, AND METHODS: Four radiation therapy centers [University Hospital of Marburg, University Hospital of Giessen, University Hospital of Berlin (Charité), Klinikum rechts der Isar der Technischen Universität München] participated in this prospective study. The workload of the different occupational groups and room occupancies for the core procedures of radiotherapy were prospectively documented during a 2-month period per center and subsequently statistically analyzed. RESULTS: The time needed per patient varied considerably between individual patients and between centers for all the evaluated procedures. The technical preparation (contouring of target volume and organs at risk, treatment planning, and approval of treatment plan) was the most time-consuming process taking 3 h 54 min on average. The time taken by the medical physicists for this procedure amounted to about 57%. The training part of the preparation time was 87% of the measured time for the senior physician and resident. The total workload for all involved personnel comprised 74.9 min of manpower for the first treatment, 39.7 min for a routine treatment with image guidance, and 22.8 min without image guidance. The mean room occupancy varied between 10.6 min (routine treatment without image guidance) and 23.7 min (first treatment with image guidance). CONCLUSION: The prospective data presented here allow for an estimate of the required machine time and manpower needed for the core procedures of radiotherapy in an average radiation treatment with IMRT. However, one should be aware that a number of necessary and time-consuming activities were not evaluated in the present study.

Correlación artroscópica interobservador entre la clasificación Outerbridge e ICRS en lesiones condrales de rodilla / Knee chondral lesions: is there a relation between the Outerbridge and the ICRS classifications?

Purpose: To determine if there is a correlation between the Outerbridge and ICRS classifications for chondral lesions. Materials and Methods: 145 patients with MRI diagnosis of at least 1 knee chondral lesion were prospectively included. Each cartilage injury found at arthroscopy was classified and recorded in a database independently and blindly by two surgeons, after each procedure. One surgeon used the Outerbridge, and the other one used the ICRS classification to record the findings. Chondrallesions were grouped in 1 of the 4 ICRS major types (i.e., types 1 a and 1 b were grouped as type 1). Results: 212 chondral lesions were found in 145 patients. The level of correlation between both classifications was 84.9% (p = 0.00). The strongest correlation was found in patellar lesions (95.7%). Conclusions: There is a high correlation between the Outerbridge and the major types of 'the ICRS classification of chondral lesions in knee arthroscopic surgery.

El objetivo de este estudio es determinar la correlación que existe entre la clasificación de Outerbridge e ICRS para las lesiones condrales en cirugía artroscópica de rodilla. Ciento cuarenta y cinco pacientes sometidos a artroscopía de rodilla, con al menos una lesión condral, fueron evaluados prospectivamente por 2 cirujanos. Uno de los cirujanos registró las lesiones con la clasificación de Outerbridge y el otro según JCRS, de manera independiente y en bases de datos separadas. Las lesiones de ICRS fueron agrupadas en uno de los 4 grandes grupos (ej: la y 1b como 1). Finalmente se registraron 212 lesiones condrales, siendo el grado de correlación entre ambas clasificaciones de un 84,9% (p = 0,00). Estos resultados deben ser tomados con cautela. Sólo pretende reportar una alta coincidencia entre los diferentes grupos de una clasificación simple (Outerbridge), con una más completa (ICRS), sin pretender reemplazar una por otra.

Poly(D,L-lactide) coating is capable of enhancing osseous integration of Schanz screws in the absence of infection.

Pin loosening is a major complication in external fixation. Biological and mechanical conditions play an important role in the maintenance and enhancement of the implant-bone interface in fracture fixation. It is thought that biodegradable coatings may be capable of preventing pin track infection and pin loosening. The goal of this study was therefore to analyze the influence of a biodegradeable coating on the osseous integration of Schanz' screws during fracture treatment. Standardized osteotomies (3-mm fracture gap) of the right tibiae were performed on 16 sheep and stabilized by an AO mono-lateral external fixator. Additional, mechanically less loaded Schanz' screws were also mounted. All screws were randomly coated with biodegradable poly(D,L-lactide). The sheep were sacrificed after 9 weeks. All screws were removed and rolled on blood agar plates for microbiological analysis. Histological sections of the pin tracks were histochemically and morphometrically analyzed. Clinically, no signs of severe infection were visible. Microbiological analysis revealed 14.8% colonization by Staphylococcus aureus in the coated and 29% in the uncoated screws. Histomorphometry of the bone surrounding the Schanz' screws revealed that significantly more osseous integration had occurred on poly(D,L-lactide)-coated screws in the absence of bacterial colonization. Significantly more bone remodeling and a higher osteoclastic activity was seen near the screw-bone interface in the uncoated screw group. Up to a threefold increase in new bone formation and more severe remodeling was observed around the screw entry compared to the pin exit in all groups. Loaded screws showed significantly more callus formation around the exit sites than their less loaded counterparts. In the present study, poly(D,L-lactide) coating of Schanz' screws was found to enhance osseous integration in the absence of bacterial colonization in sheep by causing less cortical remodeling and less osteoclastic activity in the cortices compared to uncoated screws. Additionally, the coating appeared to reduce the instances of pin track infections. Mechanical loading showed an adverse effect on bone formation and remodeling. It has been shown that both biological and mechanical factors play an important role in the maintenance of osseous integrity of the pin-bone interface. Poly(D,L-lactide) coating of Schanz' screws does not prevent osseous destruction and severe bacterial colonization along the pin tracts, but can improve osseous integration of Schanz' screws in the absence of infection.

[Incidence of transmission of pathogens in intensive care units. Results of the SIR 3 study]. / Inzidenz der Ubertragung von Infektionserregern von einem Intensivpatienten zum anderen. Ergebnisse der SIR-3-Studie.

The objective of this study was to determine the incidence of episodes of transmission of nosocomial pathogens and of those pathogens leading to nosocomial infections. Over a period of 18 months all patients from 5 intensive care units (ICUs) who stayed for more than 2 days were included in this study. Surveillance of nosocomial infections was carried out and all isolates of 10 of the most frequent pathogens in ICUs (indicator pathogens) were collected and typed. A total of 28,498 patient days and 431 nosocomial infections were observed (incidence density 15.1 per 1,000 patient days), among them 278 caused by 1 of the selected indicator pathogens. A total of 141 episodes of transmissions were identified, corresponding to an incidence of episodes of transmission of 5.0 per 1,000 patient days and 41 nosocomial infections were transmission-associated, corresponding to 14.5% of all nosocomial infections. The data of this study demonstrate that even in ICUs with average nosocomial infection rates, some nosocomial infections could be avoided.

Systemic versus local application of gentamicin in prophylaxis of implant-related osteomyelitis in a rat model.

Administration of perioperative antibiotic prophylaxis is a routine procedure in orthopedic surgery. Besides systemic prophylaxis, only few techniques are established for local application of antibiotics to reduce infection related to orthopedic implants. The aim of this study was to evaluate the efficacy of locally versus systemically applied gentamicin in a rat model (n = 60). For local application, the antibiotic was delivered from a biodegradable poly(D,L-lactide) (PDLLA) coating of titanium implants. The efficacy of local prophylaxis was compared to a systemic single shot application of gentamicin as well as a combination of both administrations. Half of the animals received a weight-adopted single shot application of gentamicin 30 min prior to surgery. At surgery, the medullary cavities of the tibiae were contaminated with Staphylococcus aureus (10(2) colony forming units /CFU) and titanium Kirschner wires were implanted into the medullary canals. The implants were either uncoated, PDLLA coated, or coated with PDLLA + 10% w/w gentamicin. The animals were followed up for 42 days. X-ray examinations were performed; body weight, temperature, and the clinical condition were determined. After sacrifice, infection was evaluated by histological and microbiological analysis. All animals treated with uncoated or PDLLA-coated Kirschner wires without systemic application of the antibiotic developed osteomyelitis and all cultures of implants were tested positive on S. aureus. Implant-related osteomyelitis could be prevented by prophylaxis of systemically applied gentamicin in 15% of animals. In contrast, local application of gentamicin delivered from a PDLLA coating was more effective. Onset of infection could be prevented in 90% of animals treated with gentamicin coated Kirschner wires, and in 80% of the animals that were treated with a combination of local and systemic application. The local application from PDLLA-coated implants might support systemic antibiotic prophylaxis in preventing implant-associated osteomyelitis.

A new model of implant-related osteomyelitis in rats.

Infection related to osteosynthesis often has dramatic consequences for the patient. Prolonged hospitalization with systemic antibiotic therapy, several revision procedures, possible amputation, and even death may occur. To investigate the pathology of infection in orthopedic surgery, a new rat model of implant related osteomyelitis was developed. Three different concentrations (10(6), 10(3), and 10(2) colony-forming units (CFU)/10 microl) of Staphylococcus aureus were inoculated into the tibial medullary cavity with simultaneous insertion of a titanium Kirschner wire. Controls received phosphate-buffered saline (PBS). Each group consisted of 10 animals. Animals were followed for 4 weeks until sacrifice. X-rays of the tibiae were taken weekly, blood counts were analyzed, and body temperature and weight were determined. After sacrifice, infection was evaluated by histological and microbiological investigations. All animals inoculated with Staph. aureus in either concentration developed microbiological, histological, and radiological signs of osteomyelitis in correlation to the amount of inoculated bacteria. X-rays clearly revealed osseous destruction after 14 days with progression of osteomyelitis during the following weeks. CFU/g bone and bone weight after sacrifice showed dependence on the amount of inoculated CFU. The histological results confirmed the radiological findings. No significant changes in blood counts, body weight, and body temperature between the groups could be observed. The results demonstrate that it is possible to develop a model of implant-related osteomyelitis in rats with dependence on the amount of inoculated bacteria. No other promoters of infection besides intramedullary insertion of titanium Kirschner wires were used in this model.

Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats.

Antibiotic prophylaxis is a routine procedure in orthopedic surgery. Various local antibiotic delivery techniques are used to reduce bone- and soft tissue-related infection. The objective of this study was to evaluate the efficacy of a new biodegradable, gentamicin-loaded poly(D,L-lactide) (PDLLA) coating of orthopedic devices in preventing implant-related osteomyelitis. The medullary cavities of tibiae in 30 Sprague Dawley rats were contaminated with Staphylococcus aureus (10(3) colony forming units). Simultaneously titanium Kirschner wires, uncoated (group II), coated with PDLLA (group III), or coated with PDLLA + 10% gentamicin (group IV), were implanted. Ten animals that received phosphate-buffered saline and uncoated Kirschner wires served as controls (group I). Follow-up was 6 weeks. In weekly intervals X-rays of the tibiae were performed, blood counts were taken, and body temperature and weight were determined. After sacrifice infection was evaluated by histological and microbiological analysis. All animals of groups II and III developed microbiological, histological, and radiological signs of infection, including osseous destruction and soft tissue swelling. All animals of the control group remained sterile. Cultures of implants of group IV showed significantly reduced bacterial growth compared to cultures of groups II and III, and three implants of group IV remained sterile. Further radiological and histological signs of infection were significantly reduced in the gentamicin-coated group compared to groups II and III. No significant differences in body weight, body temperature, and blood parameters between all groups were observed. Local application of antibiotic-coated orthopedic devices containing PDLLA and 10% gentamicin significantly reduced implant-related infection in this animal model.

3-Phenyl-5-acyloxymethyl-2H,5H-furan-2-ones: synthesis and biological activity of a novel group of potential antifungal drugs.

3-(Substituted phenyl)-5-acyloxymethyl-2H,5H-furan-2-ones related to the natural product (-)incrustoporine were synthesized and their in vitro antifungal activity evaluated. The compounds with halogen substituents on the phenyl ring displayed much higher antifungal effect against Aspergillus fumigatus than selected representatives of azole antifungal drugs. In particular, the activity (1.34 microg/mL) of the most promising derivative, 3-(3,4-dichlorophenyl)-5-pivaloyloxymethyl-2H,5H-furan-2-one, was comparable to that of amphotericin B (0.5 microg/mL). Preliminary evaluation of the toxicity of the compound was carried out as well. Considering the size and properties of these molecules in comparison with those of amphotericin B, further development of this novel group of antifungals may lead to substances with better pharmacological profiles than that of the standard anti-Aspergillus drug.

Prediction of a surface state and a related surface insulator-metal transition for the (100) surface of stochiometric EuO.

We calculate the temperature and layer-dependent electronic structure of a 20-layer EuO(100) film using a combination of first-principles and model calculation based on the ferromagnetic Kondo-lattice model. The results suggest the existence of a EuO(100) surface state which can lead to a surface insulator-metal transition.

Single-stage revision using an uncemented, porous-coated, anatomic endoprosthesis in two dogs: case report.

OBJECTIVE: To describe the clinical and radiographic features of septic and aseptic failure of two femoral endoprostheses and their successful revision. STUDY DESIGN: Case report. ANIMALS OR SAMPLE POPULATION: Two skeletally mature male research dogs. METHODS: An uncemented porous-coated anatomic (PCA) endoprosthesis was implanted in a single-stage revision procedure after thorough debridement and lavage of the femoral canal. An autogenous cancellous bone graft was used in dog 2 (aseptic loosening). Serial clinical and radiographic examinations were performed postoperatively. The dogs were euthanatized 1 year (dog 1) and 2 years (dog 2) after revision surgery, and necropsy was performed. High-resolution contact radiographs and histopathologic evaluation of femoral sections were obtained. RESULTS: The cause of implant failure was septic loosening in dog 1 and aseptic loosening in dog 2. In both dogs, clinical function returned to normal after revision. Serial radiographic assessment after revision documented disappearance of the bone pedestal and the periprosthetic lucency. Cancellous hypertrophy seen adjacent to the proximal porous-coated region of the implants provided radiographic evidence of bony fixation. Histological evaluation of femoral sections documented successful implant integration with bone and fibrous tissue. CONCLUSION: Revision with an uncemented implant in a single-stage procedure was successful in the two dogs described in this report. CLINICAL RELEVANCE: This report provides a detailed description of the clinical course and serial radiographic assessment of septic and aseptic loosening of two femoral endoprostheses. Single-stage revision is a potential treatment for either condition as demonstrated by the successful outcome in these two dogs.

Anion-selective membrane electrodes based on metalloporphyrins: The influence of lipophilic anionic and cationic sites on potentiometric selectivity.

The role of lipophilic anionic and cationic additives on the potentiometric anion selectivities of polymer membrane electrodes prepared with various metalloporphyrins as anion selective ionophores is examined. The presence of lipophilic anionic sites (e.g. tetraphenylborate derivatives) is shown to enhance the non-Hofmeister anion selectivities of membranes doped with In(III) and Sn(IV) porphyrins. In contrast, membranes containing Co(III) porphyrins require the addition of lipophilic cationic sites (e.g. tridodecylmethylammonium ions) in order to achieve optimal anion selectivity (for nitrite and thiocyanate) as well as rapid and reversible Nernstian response toward these anionic species. These experimental results coupled with appropriate theoretical models that predict the effect of lipophilic anion and cation sites on the selectivities of membranes doped with either neutral or charged carrier type ionophores may be used to determine the operative ionophore mechanism of each metalloporphyrin complex within the organic membrane phase.

Radiographic assessment of a canine uncemented porous-coated anatomic total hip prosthesis.

Thirty uncemented porous-coated anatomic total hip prostheses in 24 dogs were evaluated radiographically at 6 months, 12 months, or 18 months after arthroplasty. All dogs were fully weight bearing and free of lameness at the time of follow-up. Radiographs were assessed for prosthetic component alignment, percentage of femoral canal fill, resorptive and formative bony changes, and changes at the implant bone interface. No evidence of infection, loosening, or failure of component fixation was seen. Settling of the acetabular component and subsidence of the femoral stem was seen early after surgery. Cortical atrophy was seen in all femurs and was the most significant bony remodeling change. Early results of clinical and radiographic evaluation of uncemented total hip arthroplasty in dogs have been encouraging.

Quantitative ingrowth analysis of a porous-coated acetabular component in a canine model.

Histomorphometric analysis of bone ingrowth into a porous-coated acetabular component was evaluated in a canine model. A total of nine prostheses were evaluated, 3 at 6 months, 3 at 12 months, and 3 at 24 months after implantation. All implants were grossly stable at the time of retrieval. The mean percentage of bone ingrowth was 12% at 6 months, 24% at 12 months, and 24% at 24 months. Narrow radiolucent lines noted on microradiographs were more evident at the 6 month time period than at the 12 or 24 month time periods. Bone ingrowth into a porous-coated acetabular component in a weight-bearing model may continue beyond the 6 month time period, and early evaluation of bone ingrowth may underestimate final bone ingrowth.

Association between Staphylococcus aureus nasopharyngeal colonization and septicemia in patients infected with the human immunodeficiency virus.

In an attempt to identify risk factors for Staphylococcus aureus septicemia, 136 consecutive HIV-infected patients were investigated for the presence of nasopharyngeal colonization with Staphylococcus aureus and subsequent Staphylococcus aureus infection. Sixty of 136 (44.1%) HIV-infected patients had staphylococci which were detected in the nasopharynx on initial culture compared to 12 of 39 (30.8%) patients with chronic diseases and 11 of 47 (23.4%) healthy hospital staff. Another 12 HIV-infected subjects proved to be Staphylococcus aureus carriers on follow-up cultures. Patients with full-blown AIDS had a higher carriage rate compared to subjects who were only HIV-positive (p < 0.05), indicating that Staphylococcus aureus colonized patients were more severely ill. Eight patients with Staphylococcus aureus septicemia were observed, all of whom were carriers; no septicemia occurred in the non-colonized patients (p < 0.01). Colonized patients with neutropenia (< 1000/microliters) were significantly more likely to develop septicemia (p < 0.01). Nasopharyngeal colonization with Staphylococcus aureus and the presence of an indwelling catheter were established to be factors that help identify patients at risk of acquiring subsequent Staphylococcus aureus infection.

Radiographic criteria for evaluation of uncemented total hip replacement in dogs.

A zonal analysis system and corresponding nomenclature were developed to describe the location and nature of radiographic changes in canine uncemented total hip arthroplasties. Criteria to assess prosthetic component alignment, percentage of femoral canal fill, resorptive and formative bony changes, and alterations in the bone at the implant-bone interface were derived by studying serial radiographs of 100 consecutive canine uncemented total hip arthroplasties for up to 30 months after surgery.