Attributes of leadership skill development in high-performance pre-hospital medical teams: results of an international multi-service prospective study.

BACKGROUNDS: Team leadership skills of physicians working in high-performing medical teams are directly related to outcome. It is currently unclear how these skills can best be developed. Therefore, in this multi-national cross-sectional prospective study, we explored the development of these skills in relation to physician-, organization- and training characteristics of Helicopter Emergency Medicine Service (HEMS) physicians from services in Europe, the United States of America and Australia. METHODS: Physicians were asked to complete a survey regarding their HEMS service, training, and background as well as a full Leader Behavior Description Questionnaire (LBDQ). Primary outcomes were the 12 leadership subdomain scores as described in the LBDQ. Secondary outcome measures were the association of LBDQ subdomain scores with specific physician-, organization- or training characteristics and self-reported ways to improve leadership skills in HEMS physicians. RESULTS: In total, 120 HEMS physicians completed the questionnaire. Overall, leadership LBDQ subdomain scores were high (10 out of 12 subdomains exceeded 70% of the maximum score). Whereas physician characteristics such as experience or base-specialty were unrelated to leadership qualities, both organization- and training characteristics were important determinants of leadership skill development. Attention to leadership skills during service induction, ongoing leadership training, having standards in place to ensure (regular) scenario training and holding structured mission debriefs each correlated with multiple LBDQ subdomain scores. CONCLUSIONS: Ongoing training of leadership skills should be stimulated and facilitated by organizations as it contributes to higher levels of proficiency, which may translate into a positive effect on patient outcomes. TRIAL REGISTRATION: Not applicable.

Genetic ancestry in relation to the metabolic response to a US versus traditional Mexican diet: a randomized crossover feeding trial among women of Mexican descent.

BACKGROUND/OBJECTIVES: Certain populations with a large proportion of indigenous American (IA) genetic ancestry may be evolutionarily adapted to traditional diets high in legumes and complex carbohydrates, and may have a detrimental metabolic response to US diets high in refined carbohydrates and added sugars. We tested whether IA ancestry modified the metabolic response to a US versus traditional Mexican diet in a controlled dietary intervention. SUBJECTS/METHODS: First and second generation Mexican immigrant women (n=53) completed a randomized crossover feeding trial testing the effects of a US versus traditional Mexican diet. The metabolic response to the diets was measured by fasting serum concentrations of glucose, insulin, insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), adiponectin, C-reactive protein, interleukin-6 and computed homeostasis model assessment for insulin resistance (HOMAIR). Blood collected at baseline was used for genotyping, and estimation of African, European and IA ancestries with the use of 214 ancestry informative markers. RESULTS: The genetic ancestral background was 56% IA, 38% European and 6% African. Women in the highest IA ancestry tertile (>62%) were shorter in height, less educated and less acculturated to the US lifestyle, and tended to have higher waist-to-hip ratio compared with women in the middle and lowest IA ancestry tertiles, respectively. Compared with the US diet, the traditional Mexican diet tended to reduce glucose, insulin, IGF-1, IGFBP-3 and HOMAIR among women in the middle IA ancestry group (IA ancestry ⩽45-62%), whereas having no effect on biomarkers related to inflammation. CONCLUSIONS: We observed modest interactions between IA ancestry and the metabolic response to a US versus traditional Mexican diet among Mexican immigrant women.

[The organization of Jewish dentists in pre-Israel Palestine].

The first modern dental institutes were established in Europe and in the USA during the 1840s. At that period there wasn't a single qualified doctor in Palestine, not to mention a professional dentist. A couple of decades later, as the number of Christian pilgrims grew, some modern hospitals were established and a few non-Jewish dentists opened their clinics in Jerusalem, which was then and in the following decades, the region's largest city. In Europe, dentistry became a popular profession among Jews in general and among Jewish women in particular. The first Jewish dentist settled in Jerusalem in the mid-1880s. Other dentists were slow to arrive and their number began to grow only after the turn of the 20th century. Their professional education varied from those who were trained as apprentices by other dentists to those which studied a couple of years in an academic dental school. The devastation caused by WWI prompted American-Zionist organizations to send a special medical unit to Palestine in 1918. Along medical supplies it also brought a small group of doctors and dentists. The two American dentists that decided to remain in Palestine took upon themselves to spread their medical and scientific knowledge. They also organized the dentists, whose number grew considerably during the 1920s, and called the authorities to regulate the dental profession. In 1926 the British authorities issued a decree regulating all medical professions. It demanded that dental practitioners will be licensed after proving their previous studies and professional knowledge. In 1931, local dentists' organizations decided to establish the Palestine Dental Association. Five years later it was accepted as a member by the International Dental Federation (FDI) and was recognized by the local authorities. Since the 1930s, prominent Jewish dentists from abroad were invited to come to Palestine to lecture, and local dentists participated in international conferences. This prompted the first scientific publications. At the same time dentists published articles in the daily press in which they educated the public on dental hygiene and on modern dental techniques. This momentum was halted in the early 1940s as result of WWII and the Holocaust, but was quick to resume immediately thereafter. 1944 saw the publication of a professional dental Journal, which this issue is a continuation of. By the time the state of Israel was established in 1948, it had more than 900 active dentists, most of them organized in the Israel Dental Association. The only element which was still required to bridge the gap between the dentists in Israel and those in the rest of the modern world was an academic dental school. After more than 20 years in making, the school was opened in 1953 in Jerusalem. From that time on, Israel's dentistry enjoys a worldwide reputation and its dental school graduates teach and lecture in universities and in many dental forums around the globe.

An extreme value theory approach for the early detection of time clusters. A simulation-based assessment and an illustration to the surveillance of Salmonella.

We propose a new method that could be part of a warning system for the early detection of time clusters applied to public health surveillance data. This method is based on the extreme value theory (EVT). To any new count of a particular infection reported to a surveillance system, we associate a return period that corresponds to the time that we expect to be able to see again such a level. If such a level is reached, an alarm is generated. Although standard EVT is only defined in the context of continuous observations, our approach allows to handle the case of discrete observations occurring in the public health surveillance framework. Moreover, it applies without any assumption on the underlying unknown distribution function. The performance of our method is assessed on an extensive simulation study and is illustrated on real data from Salmonella surveillance in France.

Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol-induced atherosclerosis.

BACKGROUND AND PURPOSE: Erectile dysfunction correlates with cardiovascular disease and its common risk factors due to the development of endothelial dysfunction. Positive effects on endothelial and erectile function have been described for substances inhibiting the renin-angiotensin-system. Here, we investigated in an atherosclerosis model, whether telmisartan (angiotensin receptor blocker) and ramipril (angiotensin converting enzyme inhibitor) are equivalent or the combination of both is superior in improving endothelial function in the aorta and the corpus cavernosum and in reducing atherosclerosis. EXPERIMENTAL APPROACH: Wild-type (WT, C57/B6) and apolipoprotein-E-deficient (ApoE(-/-) ) mice were treated with a cholesterol-rich diet for 8 weeks. ApoE(-/-) mice were supplemented with either telmisartan (20 mg·kg(-1) ·day(-1) ), ramipril (2.5 mg·kg(-1) ·day(-1) ) or the combination thereof. KEY RESULTS: Systolic blood pressure significantly decreased in treatment groups (P < 0.001), with significantly smaller reduction under ramipril monotherapy (P < 0.05). Endothelial function (assessed by pharmacological stimulation of aortic rings and corpus cavernosum in organ bath chambers) was impaired in ApoE(-/-) mice compared to WT animals, which was improved by all three treatments to a comparable extent (P < 0.05). Atherosclerotic lesion size in the ascending aorta and aortic sinus (P < 0.001), the amount of lipid peroxides in cavernosal and aortic tissue (P < 0.05) and free radical load (dihydroethidium-stain) (P < 0.05) were enhanced in untreated ApoE(-/-) mice in comparison to WT animals and were significantly reduced by either treatment. In penile tissue, expression of eNOS could be restored by renin-angiotensin-aldosterone system blockade. CONCLUSIONS AND IMPLICATIONS: Telmisartan and ramipril significantly improved endothelial function of aortic and cavernosal tissues in ApoE(-/-) via reduction of oxidative stress. Combination of both agents does not enhance beneficial effects significantly.

Cardiovascular risk, drugs and erectile function--a systematic analysis.

AIMS: Erectile dysfunction is a major problem with an increasing prevalence in cardiovascular high-risk patients due to its association with cardiovascular risk factors. Drugs used for evidence-based treatment of cardiovascular diseases have been reported to decrease erectile function, but possible mechanisms are poorly characterised. METHODS: MEDLINE, EMBASE and Cochrane Registry search were performed including manuscripts until January 2010. Searching terms are: 'erectile dysfunction or impotence' in combination with 'ACE-inhibitors', 'angiotensin', 'beta-blockers', 'calcium antagonist' and 'diuretics'. Animal studies, letters, reviews, case-reports and manuscripts other than English language and trials dealing with combination treatment are excluded. RESULTS: Analysis of literature revealed five epidemiological trials evaluating the effect of different cardiovascular drugs on erectile function. There were eight trials evaluating the effect of beta-blockers, five trials evaluating the effect of ace-inhibitors or angiotensin-receptor-blockers and one trial evaluating the effect of diuretics on erectile function. Results of these trials demonstrate that only thiazide diuretics and beta-blockers except nebivolol may adversely influence erectile function. ACE-inhibitors, angiotensin-receptor-blockers and calcium-channel-blockers are reported to have no relevant or even a positive effect on erectile function. CONCLUSION: Inappropriate patients' concerns about adverse effects of cardiovascular drugs on erectile function might limit the use of important medications in cardiovascular high-risk patients. Knowledge about the effects of drug-treatments on erectile function and about the major role of the endothelium in penile function might improve patients' adherence to evidence based treatment of cardiovascular diseases.

Zetos: a culture loading system for trabecular bone. Investigation of different loading signal intensities on bovine bone cylinders.

The objective of this investigation was to test the effects of different intensities (1000, 1500, 2000, 3000, and 4000 microstrain) of a physiological loading signal (jumping) on trabecular bone stiffness and osteoid thickness using the ZETOS culture and loading system. Fourty eight bovine bone samples were randomised equally across 6 groups: 5 loading groups and 1 control group. The bone samples were cultured for 26 days (DMEM high glucose medium) and subjected to mechanical stress on 23 days. The stiffness of the samples was determined each day before loading in the loading groups and every 3rd day in the control group. The stiffness measurements in the loaded groups were significantly higher than in the control group. The degree of stiffness increased continuously throughout the observation period in the 1500, 2000, and 3000 microstrain groups. Maximum stiffness was achieved in the 4000 microstrain after a very short time (8th loading day) and then remained constant to the end of the investigation. The osteoid thickness in this group was, however, not higher than in the 2000 and 3000 microstrain groups. The 2000 microstrain group showed the highest proportion of newly formed osteoid. The amounts of osteoid deposited in the 2000, 3000 and 4000 microstrain groups were significantly greater than in the control group. Moreover, a correlation between increasing intensity of the signal and increase in osteoid deposition was observed. Histological investigations were conducted on non-decalcified bone and showed a well-preserved trabecular architecture and cell morphology.

Gamma irradiation. An effective procedure for bone banks, but does it make sense from an osteobiological perspective?

BACKGROUND: Bone grafts promote bone healing by supplying a three-dimensional structure that supports bone ingrowth. Autologous bone therefore still remains the "gold standard" for grafts. Unfortunately, autologous bone grafts are associated with an increased morbidity. In order to avoid such problems, intensive research has been carried out on alternative materials such as allogeneic bone. However, its use is dependent on bone banks and its availability is limited. Gamma irradiation is now becoming established as a procedure for inactivating bacteria, fungal spores and viruses. Its effects on the biomechanical properties of bone have been analyzed in numerous studies. However, the current literature provides little information as to the effects of gamma sterilization on the osteobiology of allogeneic bone grafts. PURPOSE: The purpose of this study was to evaluate the effect of gamma-sterilized bone grafts on immunocompetent cells by an in vitro model (a culture of human bone marrow cells). METHODS: We decided to use the model of human bone marrow cells in culture for the in vitro analysis because the physiological conditions in the human body can best be simulated in this model and the observed reactions are applicable to humans. RESULTS AND INTERPRETATION: In sum, we found a maximum immune response in gamma-irradiated bone grafts, which, interpreted as a sole result, must be seen as a negative biological effect. However, in view of the good clinical results for gamma-sterilized bone grafts other influences would seem to be the determining factors in clinical outcome. Further research is needed to gain a more exact understanding of these factors.

Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols.

OBJECTIVE: We investigated the serum phytosterol responses of heterozygous relatives of sitosterolemia patients to diets enriched in phytosterols or stanols. DESIGN: Randomized double-blind crossover design. SETTING: Muenster, Germany. SUBJECTS: Eight heterozygous and 13 control subjects were recruited. One heterozygote and three controls dropped out. INTERVENTIONS: Seven heterozygotes and 10 controls received daily portions of margarine containing 2 g of plant sterols, 2 g of stanols or a control margarine for 6 weeks each in a randomized order. These phases were intercepted by wash-out periods of 6 weeks each. RESULTS: Compared to the control period, serum phytosterol concentrations increased overall by more than 20% when subjects consumed the plant sterol margarine (F((1,15))=8.719, P=0.01), with no significant difference between heterozygotes (mean +14.5 (s.d. 17.2) micromol/l, +23.0%) and controls (+4.9 (9.9) micromol/l, +20.5%; F((1,15))=2.168, P=0.162), but decreased when subjects consumed the stanol-enriched margarine (F((1,15))=12.124, P=0.003), again to a similar extent in heterozygotes (-34.2 (41.2) micromol/l, -54.2%) and controls (-12.2 (9.2) micromol/l, -50.6%; F((1,15))=2.729, P=0.119). The lowest total serum concentrations of cholesterol and phytosterols were seen after the diet enriched in stanols. Serum stanol concentrations increased on this diet, but on a very low level and never exceeded 0.05% of serum cholesterol levels in any subject. CONCLUSIONS: Serum phytosterol concentrations increased only moderately in heterozygotes consuming a diet enriched in phytosterols, indicating that they retained considerable capacity to excrete phytosterols even at higher intakes.

[Comparative in vitro analysis of vacuum plasma-sprayed titanium implants--evaluation of OPG, Osteokalzin and AP expression]. / Vergleichende In-vitro-Analyse vakuum-plasmagespritzter Titanprobenkörper--Evaluation der OPG-, Osteokalzin- und AP-Expression.

INTRODUCTION: The purpose of this study was to evaluate the influence of different surface topographies on the expression of bone cell-associated proteins, such as osteoprotegerin (OPG), osteocalcin and alkaline phosphatase (AP), and the production of the extracellular matrix (ECM) in vitro. Another aspect was the question as to whether a hydroxyapatite (HA) coating offers additional advantages. Vacuum plasma-sprayed (VPS) pure titanium was used to generate different surface topographies. MATERIALS AND METHODS: The in vitro response of human bone marrow cells to VPS implants (porosity ranging from 25 to 50%, pore size ranging from 50 to 200 microm and roughness ranging from 0.191 to 0.547 mm) and cancellous structured titanium (cs-Ti) as a reference material (55% porosity, pore size of 500 microm, roughness 0.836 mm) were compared. The expression of bone cell-associated proteins, such as OPG, osteocalcin and alkaline phosphatase (AP), was evaluated. Scanning electron microscopy (SEM) was used to judge the production of ECM. RESULTS: All implant materials induced the release of OPG, osteocalcin and AP. Significant differences were evident between the cs-Ti and the different VPS-Ti surface structures. There was no difference in the response between the VPS-Ti surfaces. SEM showed a dense and increased production of ECM on the VPS-Ti surfaces. An additional HA coating caused a faster production of ECM and higher levels of OPG. CONCLUSIONS: The in vitro data presented here demonstrate the superiority of VPS-Ti surfaces over cs-Ti, which is already in clinical use. Differences between the VPS-Ti surfaces were not evident. Presumably, VPS-Ti surfaces offer good prerequisites for a successful integration of the implant in the surrounding tissue. An additional HA coating could influence these events positively.

[Biocompatibility testing of different sterilised or disinfected allogenous bone grafts in comparison to the gold standard of autologous bone grafts--an "in vitro" analysis of immunomodulation]. / Biokompatibilitätstestung unterschiedlich sterilisierter bzw. desinfizierter allogener Knochentransplantate im Vergleich zum Goldstandard der autologen Knochenspende--Eine "In-vitro"-Analyse der Immunmodulation.

INTRODUCTION: Repair of large skeletal defects using bone allografts has become a routine procedure in orthopaedic and trauma surgery. Different procedures of sterilisation (82.5 degrees C disinfection; 121 degrees C autoclaving; PES; Tutoplast; 25 kGy gamma irradiation) are available to inactivate bacteria and fungi, including their spores, as well as viruses in human bone allografts. The efficiency of these procedures has been proven. However, the effects on the cellular response are rarely investigated. This present in vitro study investigates the immunological answer of human bone marrow cells to human allogenous and autologous bone platelets which were sterilised by different methods. MATERIALS AND METHODS: Human bone marrow cells and the bone platelets were harvested from patients undergoing a total hip replacement. All patients provided informed consent. Human bone platelets, 10 mm in diameter, 3 mm in height, were produced from femoral heads which were removed within the scope of total hip replacements. They were sterilised by different procedures or were disinfected (gamma radiotherapy, PES/ethanol treatment, Tutoplast procedure, 121 degrees C autoclaving, > 82.5 degrees C thermodisinfection). In addition, an autologous in vitro bone donation was simulated and compared with the allogenous bone grafts. Endobon was evaluated as a bovine hydroxyapatite ceramic. As control a human bone marrow cell culture without bone platelets was used. Over a period of four weeks the changes of the immunogenic cell populations were analysed in vitro (FACS analysis). Light and scanning microscopy were done to reveal morphological differences. As a vitality test the trypan-blue staining was performed. RESULTS: Light and scanning microscopy demonstrated large differences between the various sterilisation and disinfection methods. After 4 weeks the autologous bone platelets were completely covered with homogenously distributed human osteoblast like cells. The heat-sterilised/disinfected transplants demonstrated similar effects compared to the autologous bone grafts while the irradiated bone platelets demonstrated less cell coverage. 2/3 of the cells were vital on average after four weeks, with the exception of the irradiated bone platelets. The FACS analysis revealed in comparison to the control group provable differences in the immunological answer for the autologous bone donation as well as for the differently sterilised or disinfected allogenous bone grafts. The heat sterilisation or, respectively, disinfection methods compared to the autologous bone donation demonstrated almost similar in vitro effects. By far the worst results, characterised by an excessively increased portion of cytotoxic T-cells and a decreased amount of viable cells, were seen in the 25 kGy gamma irradiation samples. CONCLUSIONS: The results demonstrate the influence of the different sterilisation and disinfection procedures on the differentiation of human marrow cells (host). Similar in vitro effects were seen for the autologous and heat-treated bone platelets. The treatment of allogenous bone grafts with PES/ethanol and the Tutoplast procedures showed, just as Endobon, only low differences in comparison with the control cultures. The worse results in the case of the irradiated bone platelets may be explained by the production of free radicals which led to an excessive cell death.

[Cell differentiation of a human bone marrow cell culture under the influence of UHMW-PE debris]. / Zelldifferenzierung einer humanen Knochenmarkzellkultur unter dem Einfluss von UHMW-PE Abriebpartikeln.

AIM: The purpose of the present study was to evaluate the influence of ultra-high-molecular-weight polyethylene (UHMW-PE), which is the major constituent of the material debris formed as a result of orthopaedic implant wear, on the cellular differentiation in a modified in vitro model. METHODS: UHMW-PE particles (Ø < or = 7.5 microm) were suspended in soluble collagen type I and subsequently solidified in different concentrations (10(5), 10(6) and 10(7) particles per well) on the bottom of the wells. Human bone marrow cells in a concentration of 3 x 10(6) cells per well were seeded on the collagen-particle substrate and maintained for up to 72 h. The response of the cells to the particles was examined by light microscopy, scanning electron microscopy and FACS analysis compared to cells on control collagen surfaces without any particles. RESULTS: Light and scanning microscopic evaluation revealed that the UHMW-PE particles, which had built large conglomerates (Ø 7.5 microm), were mainly surrounded by the cells and less phagocytosed. The results of the FACS analysis revealed significant differences in CD3/CD4 positive, CD14 positive and CD19 positive cells (p < 0.05). A significant elevation of CD3/CD4 positive and CD14 positive cells (p < 0.05) was observed after the period of culture (72 h) whereas a significant decrease could be detected in the case of CD19 positive cells. CONCLUSION: The results demonstrate that the particle-induced response by UHMW-PE limits itself not only to the particle macrophage contact but influences also the differentiation of the bone marrow. Moreover, the results confirm that the present method is useful to evaluate the in vitro effects of UHMW-PE wear particles with direct particle cell contact. Although the particles built large conglomerates, it could be shown that a change of the immune-competent cells also occurred.

[Cytokine profile of a human bone marrow cell culture under the influence of UHMW-PE wear particles]. / Zytokinprofil einer humanen Knochenmarkzellkultur unter dem Einfluss von UHMW-PE Abriebpartikeln.

There is considerable evidence that orthopaedic wear debris plays a crucial role in the pathology of aseptic loosening of joint prostheses. The purpose of the present study was to evaluate the influence of ultra-high-molecular-weight polyethylene (UHMW-PE) on the cytokine response in a modified in vitro model. UHMW-PE particles (psi < 7.5 microm) were suspended in soluble collagen type I and subsequently solidified in different concentrations (105,106 and 107 particles per well) on the bottom of the wells. Human bone marrow cells in a concentration of 3 x 106 cells per well were seeded on the collagen-particle substrata and maintained for up to 12 days. The cytokine response (IL-1_, IL-6 and TNF-_) of the cells to the particles were examined by ELISA compared to cells on control collagen surfaces without any particles. Assays for viability using LDH activity were done immediately. Light and scanning microscopic evaluation revealed that the UHMWPE particles, which have built large conglomerates (psi7.5_m), were mainly surrounded by the cells and less phagocytosed. The results of the cytokine release revealed significant differences in interleukin (IL)6, tumor necrosis factor (TNF)- _ and IL-1beta. The cell viability was not affected by the UHMW-PE particles. The results demonstrate that the particle induced cytokine response by UHMW-PE is mainly by the release of Interleukin 6 and TNF- _. Moreover the results confirm that the present method is useful to evaluate the in vitro effects of UHMW-PE wear particles with direct particle cell contact.

Dietary cholesterol, atherosclerosis and coronary heart disease.

As early as at the beginning of the last century, animal studies have pointed to a causal role of dietary cholesterol in atherogenesis. In humans, however, most observational studies have not provided convincing evidence for an impact of cholesterol intake on coronary heart disease (CHD). Rather, these studies have consistently established a close association between a certain eating pattern and the risk of CHD. This eating pattern has usually been characterized by a high intake of total fat, saturated fatty acids (SFA) and cholesterol, and a low intake of fiber and polyunsaturated fatty acids (PUFA). In typical western diets the amounts of total fat, SFA, and cholesterol are strongly correlated with each other, while they are negatively related to the intake of fiber and PUFA. Thus, it has not been possible to determine whether the association between the above mentioned eating pattern and CHD is due to the high consumption of SFA, cholesterol, both, or an insufficient supply of one or more protective factors such as fiber or PUFA. As the consumption of eggs leads to a high intake of cholesterol without necessarily resulting in high uptake levels of SFA and total fat, several groups have tried to elucidate the effect of cholesterol by investigating the relationship between the consumption of eggs and the development of CHD. Based on these studies, the association between dietary cholesterol and CHD risk is, if anything, minor in nature. This is consistent with the finding that an increase in dietary cholesterol intake results in only a minimal increase in the total/high-density lipoprotein cholesterol ratio. Taken together these studies suggest that the association between dietary cholesterol and CHD is small, as most subjects can effectively adapt to higher levels of cholesterol intake. Nevertheless, lowering dietary cholesterol content might reduce the risk of CHD considerably in a subgroup of individuals who are highly responsive to changes in cholesterol intake.

Role of protein kinase C-epsilon (PKCepsilon) in isoflurane-induced cardioprotection.

BACKGROUND: Volatile anaesthetics precondition the heart against infarction, an effect partly mediated by activation of the epsilon isoform of protein kinase C (PKCepsilon). We investigated whether cardioprotection by activation of PKCepsilon depends on the isoflurane concentration. METHODS: Anaesthetized rats underwent 25 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups (n=10 in each group): isoflurane preconditioning induced by 15 min administration of 0.4 minimal alveolar concentration (MAC) (0.4MAC), 1 MAC (1MAC) or 1.75 MAC (1.75MAC) followed by 10 min washout before ischaemia. Each protocol was repeated in the presence of the PKC inhibitor staurosporine (10 microg kg(-1)): 0.4MAC+S, 1MAC+S and 1.75MAC+S. Controls were untreated (CON) and additional hearts received staurosporine without isoflurane (S). In a second set of experiments (n=6 in each group) hearts were excised before the infarct inducing ischaemia, and phosphorylation and translocation of PKCepsilon were determined by western blot analysis. RESULTS: Isoflurane reduced infarct size from a mean of 61(SEM 2)% of the area at risk in controls to 20(1)% (0.4MAC), 26(3)% (1MAC) and 30(1)% (1.75MAC) (all P<0.01 vs CON or S). This protection was partially reversed by administration of staurosporine in the 0.4MAC+S group (30[2]%; P<0.05 vs 0.4MAC) group, but not after administration of 1 MAC or 1.75 MAC isoflurane (26[2]% and 31[2]%, respectively). Thus 0.4MAC increased PKCepsilon phosphorylation, and this effect was blocked by staurosporine. Higher concentrations of isoflurane did not change PKCepsilon phosphorylation. PKCepsilon was translocated to the membrane fraction after administration of 0.4 MAC isoflurane, but not after 1.0 or 1.75 MAC. CONCLUSIONS: Although isoflurane preconditioning resulted in a reduction in infarct size at all concentrations used, the protection was mediated by phosphorylation and translocation of PKCepsilon only at 0.4 MAC.

[Histomorphometric evaluation of bone ingrowth of porous titanium by a computer-assisted analyzing system]. / Histomorphometrische Evaluation poröser Titanprobenkörper anhand eines computergestützten Bildanalysesystems.

The objective of this study was to evaluate the bone ingrowth of a new vacuum plasma sprayed titanium surface (vps-ti) in comparison to cs-titanium implants in a göttinger minipig model. Fifteen göttinger minipigs each received the two implants, vacuum plasma sprayed titanium with a porosity of 50% and a pore size of 200 microm (vps-ti) and an implant with a similar porosity but a different pore size 500 microm (cs-ti), at the proximal femur metaphysis by press-fit technique. The pigs were euthanized at three different postsurgical periods: 4, 8 and 12 weeks. Each femur was harvested and qualitative (macroscopic and microscopic) and quantitative (histomorphometric) histological analysis was done on histological slides. The results indicated that there was a difference in bone ingrowth between the two implants, whereas the bone ingrowth of vps-ti was superior to cs-ti after 4 and 8 weeks healing time. 12 weeks post implantationem no statistiscal difference was evident. The pore size of 200 microm seemed superior to a pore size of 500 microm. Whether or not these effects lead to a better mechanical stability remains unanswered.

[Biocompatibility testing of various biomaterials as dependent on immune status]. / Biokompatibilitätstestung verschiedener Biomaterialien in Abhängigkeit vom Immunstatus.

INTRODUCTION: This study deals with the ingrowth behaviour of biomaterials (hydroxyapatite, cp-titanium, cobalt-chromium-molybdenum and PAEK) in relationship to the immunological competence in an animal model. Measured were the production of extracellular matrix (ECM) after implantation in non-immunocompetent naked mice and immunocompetent wild mice. Intention of the trial was to find out if either the immunological competence or the duration of implantation influences the quantity of produced ECM. In addition, the ingrowth behaviour was investigated under these conditions by using four different biomaterials. MATERIAL AND METHODS: Biomaterials (hydroxyapatite, cp-titanium, cobalt-chromium-molybdenum and PAEK) were implanted for 14 or 60 days, respectively. CLSM, SEM and SEM-EDX were used for analysis of the ECM and for measuring the distance between ECM and the biomaterials. CLSM was also used for the detection of collagen I and III as a parameter of the quality of osteointegration. RESULTS: In all cases a matrix grew on the surface of the biomaterials. The CLSM detected a co-localisation of collagen I and III. In the case of hydroxyapatite collagen I and III were found at a distance of 1 micro m over the surface. The largest space between the surface of the implant and the ECM was found in the case of PAEK. The smallest space was in the case of hydroxyapatite. In all investigated biomaterials the proportion of collagen I to collagen III varied through the duration of implantation. DISCUSSION: As is known from the literature we found different ingrowth behaviours on using different biomaterials. Furthermore, we found a statistically significant influence of the immunological competence of the host with regard to ECM production. We draw the conclusion that immunological competence improves the ingrowth behaviour of biomaterials.