Effects of Degree of Surgical Correction for Flatfoot Deformity in Patient-Specific Computational Models.

A cohort of adult acquired flatfoot deformity rigid-body models was developed to investigate the effects of isolated tendon transfer with successive levels of medializing calcaneal osteotomy (MCO). Following IRB approval, six diagnosed flatfoot sufferers were subjected to magnetic resonance imaging (MRI) and their scans used to derive patient-specific models. Single-leg stance was modeled, constrained solely through physiologic joint contact, passive soft-tissue tension, extrinsic muscle force, body weight, and without assumptions of idealized mechanical joints. Surgical effect was quantified using simulated mediolateral (ML) and anteroposterior (AP) X-rays, pedobarography, soft-tissue strains, and joint contact force. Radiographic changes varied across states with the largest average improvements for the tendon transfer (TT) + 10 mm MCO state evidenced through ML and AP talo-1st metatarsal angles. Interestingly, 12 of 14 measures showed increased deformity following TT-only, though all increases disappeared with inclusion of MCO. Plantar force distributions showed medial forefoot offloading concomitant with increases laterally such that the most corrected state had 9.0% greater lateral load. Predicted alterations in spring, deltoid, and plantar fascia soft-tissue strain agreed with prior cadaveric and computational works suggesting decreased strain medially with successive surgical repair. Finally, joint contact force demonstrated consistent medial offloading concomitant with variable increases laterally. Rigid-body modeling thus offers novel advantages for the investigation of foot/ankle biomechanics not easily measured in vivo.

A population of patient-specific adult acquired flatfoot deformity models before and after surgery.

Following IRB approval, a cohort of 3-D rigid-body computational models was created from submillimeter MRIs of clinically diagnosed Adult Acquired Flatfoot Deformity patients and employed to investigate postoperative foot/ankle function and surgical effect during single-leg stance. Models were constrained through physiologic joint contact, passive soft-tissue tension, active muscle force, full body weight, and without idealized joints. Models were validated against patient-matched controls using clinically utilized radiographic angle and distance measures and plantar force distributions in the medial forefoot, lateral forefoot, and hindfoot. Each model further predicted changes in strain for the spring ligament, deltoid ligament, and plantar fascia, as well as joint contact loads for three midfoot joints, the talonavicular, navicular-1st cuneiform, and calcaneocuboid. Radiographic agreement ranged across measures, with average absolute deviations of <5° and <4 mm indicating generally good agreement. Postoperative plantar force loading in patients and models was reduced for the medial forefoot and hindfoot concomitant with increases in the lateral forefoot. Model predicted reductions in medial soft-tissue strain and increases in lateral joint contact load were consistent with in vitro observations and elucidate the biomechanical mechanisms of repair. Thus, validated rigid-body models offer promise for the investigation of foot/ankle kinematics and biomechanical behaviors that are difficult to measure in vivo.

[Are complaints an element for health-care monitoring? Analysis of the user statistics of the federal commissioner for patient issues between 2004 and 2007]. / Beschwerden als Baustein eines gesundheitlichen Versorgungsmonitorings? Eine Nutzeranalyse des Amtes der Bundespatientenbeauftragten für den Zeitraum 2004 bis 2007.

BACKGROUND: The inclusion of patient perceptions in the assessment of health-care quality has gained in importance in recent years. The main instruments applied for this purpose are different types of patient interviews. Complaint data have rarely been used thus far. METHODS: On the basis of 19 117 complaints and inquiries to the office of the federal government commissioner for patient issues, this article examines to what extent this data source can be systematically used in health-care research and describes which groups of persons addressed their concerns to the commissioner for patient issues between the years 2004 and 2007. In this context, an investigation is done to determine whether reported or reconstructed data on sociodemographic characteristics are sufficient for analysis. A comparison with population-wide data also indicates to what extent the results can be considered representative for the concerns of patients or insurants in Germany. The letters and inquiries were subjected to a quantitative content analysis. RESULTS: The terms "gender", "region" and "insurance status" can be consistently encoded in a high percentage of those who make complaints and inquiries. The items "age" and "employment status" can be reconstructed to a lesser degree. However, a structural comparison of "responders" and "non-responders" shows that the results from the sample with these characteristics can be generalised for all concerns addressed. Data on the education and migration background were insufficient for analysis. Compared to the general population, a disproportionately high number of older and/or retired people (EM/EU pension) as well as unemployed persons and persons from Berlin and the new federal states contact the commissioner for patient issues. However, changes over time show a successive approach to population-wide distributions. CONCLUSIONS: The results recommend this unique data source for continuous coverage. The data documentation should thus be further standardised and integrated into a complaint management system that includes all relevant complaint offices in Germany.

Mechanisms underlying endothelial dysfunction in diabetes mellitus.

Incubation of endothelial cells in vitro with high concentrations of glucose activates protein kinase C (PKC) and increases nitric oxide synthase (NOS III) gene expression as well as superoxide production. The underlying mechanisms remain unknown. To address this issue in an in vivo model, diabetes was induced with streptozotocin in rats. Streptozotocin treatment led to endothelial dysfunction and increased vascular superoxide production, as assessed by lucigenin- and coelenterazine-derived chemiluminescence. The bioavailability of vascular nitric oxide (as measured by electron spin resonance) was reduced in diabetic aortas, although expression of endothelial NOS III (mRNA and protein) was markedly increased. NOS inhibition with N:(G)-nitro-L-arginine increased superoxide levels in control vessels but reduced them in diabetic vessels, identifying NOS as a superoxide source. Similarly, we found an activation of the NADPH oxidase and a 7-fold increase in gp91(phox) mRNA in diabetic vessels. In vitro PKC inhibition with chelerythrine reduced vascular superoxide in diabetic vessels, whereas it had no effect on superoxide levels in normal vessels. In vivo PKC inhibition with N:-benzoyl-staurosporine did not affect glucose levels in diabetic rats but prevented NOS III gene upregulation and NOS-mediated superoxide production, thereby restoring vascular nitric oxide bioavailability and endothelial function. The reduction of superoxide in vitro by chelerythrine and the normalization of NOS III gene expression and reduction of superoxide in vivo by N:-benzoyl-staurosporine point to a decisive role of PKC in mediating these phenomena and suggest a therapeutic potential of PKC inhibitors in the prevention or treatment of vascular complications of diabetes mellitus. The full text of this article is available at http://www.circresaha.org.

Effects of long-term nitroglycerin treatment on endothelial nitric oxide synthase (NOS III) gene expression, NOS III-mediated superoxide production, and vascular NO bioavailability.

Long-term nitroglycerin (NTG) treatment has been shown to be associated with cross-tolerance to endothelium-dependent vasodilators. It may involve increased production of reactive oxygen species (such as superoxide, O(2)(.-)) that rapidly inactivate the nitric oxide (NO) released from the endothelial cells. It remains to be elucidated, however, whether long-term treatment with NTG alters the activity and expression of the endothelial NO synthase (NOS III) and whether this enzyme can contribute to O(2)(.-) formation. We studied the influence of long-term NTG treatment on the expression of NOS III as assessed by RNase protection assay and Western blot. Tolerance was measured ex vivo in organ chamber experiments with rat aortic rings. O(2)(.-) and NO formation were quantified using lucigenin- and Cypridina luciferin analog-enhanced chemiluminescence as well as electron spin resonance (ESR) spectroscopy. Treatment of Wistar rats with NTG (Alzet osmotic minipumps, NTG concentration 10 microg x kg(-1) x min(-1)) for 3 days caused marked tolerance, cross-tolerance to the endothelium-dependent vasodilator acetylcholine, and a significant increase in O(2)(.-)-induced chemiluminescence. Tolerance was associated with a significant increase in NOS III mRNA to 236+/-28% and NOS III protein to 239+/-17%. In control vessels, the NOS inhibitor N(G)-nitro-L-arginine (L-NNA) increased the O(2)(.-)-mediated chemiluminescence, indicating that basal production of endothelium-derived NO depresses the baseline chemiluminescence signal. In the setting of tolerance, however, L-NNA decreased steady-state O(2)(.-) levels, indicating the involvement of NOS III in O(2)(.-) formation. Likewise, A23187-induced, NOS III-mediated O(2)(.-) production was more pronounced in tolerant than in control vessels. Vascular NO bioavailability as assessed with ESR spectroscopy using iron-thiocarbamate as a trap for NO was significantly reduced in tolerant vessels. Pretreatment of tolerant tissue in vitro with the protein kinase C (PKC) inhibitors reduced basal and stimulated NOS III-mediated O(2)(.-) production and partially reversed vascular tolerance. These findings suggest that NTG treatment increases the expression of a dysfunctional NOS III gene, leading to increased formation of O(2)(.-) and decreased vascular NO bioavailability. Normalization of NOS III-mediated O(2)(. -) production and improvement of tolerance with PKC inhibition suggests an important role for PKC isoforms in mediating vascular dysfunction caused by long-term NTG treatment.

Performance of an intravenous gas exchanger (IVOX) in a venovenous bypass circuit.

To analyze quantitatively the performance of the intravenacaval blood gas exchanger (IVOX), we developed a right atrium-pulmonary artery venovenous extracorporeal bypass circuit. Oxygen transfer and carbon dioxide removal were calculated at different blood flow rates, different hemoglobin levels, and during permissive hypercapnia. Oxygen transfer increased linearly with blood flow up to 41 mL/min. Likewise, O2 transfer increased linearly with hemoglobin levels up to 7.5 g/dL, but no further increases were achieved above this level. Carbon dioxide removal increased linearly as flow increased from 1.0 to 3.0 L/min but did not increase further for higher flows. Carbon dioxide removal was 45 mL/min at blood carbon dioxide tension of 42 mm Hg but increased to a maximum of 81 mL/min at a carbon dioxide tension of 90 mm Hg. We conclude that IVOX is a diffusion-limited device dependent on blood flow, hemoglobin content, and the gas pressure gradient across the membrane. Further engineering improvements are needed to improve the gas exchange performance of IVOX.