Just compensation? GAO investigating executive pay at not-for-profits.
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Biomedical subjects
Publications and source records attributed to Mark Taylor.
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BACKGROUND: Although the short-term performance of modern resurfacing hip arthroplasty is impressive, the long-term performance is still unknown. It is hypothesised that bone remodelling and the resulting changes in stress/strain distribution within the resurfaced femur influence the risk of fixation failure. METHOD: Three-dimensional finite element models and adaptive bone remodelling algorithms have been used to predict long-term changes in bone density following cemented femoral head resurfacing. Applied loading conditions include normal walking and stair climbing. The remodelling simulation was validated by comparing the results of an analysis of a proximal femur implanted with a Charnley femoral component with known clinical data in terms of bone density adaptations. FINDINGS: Resurfacing caused a reduction of strain of 20-70% in the bone underlying the implant as compared to the intact femur, immediately post operative. Elevated strains, ranging between 0.50 and 0.80% strain, were generated post-operatively around the proximal femoral neck regions, indicating a potential risk of neck fracture. However, this strain concentration was considerably reduced after bone remodelling. After remodelling, bone resorption of 60-90% was observed in the bone underlying the implant. Reduction in bone density of 5-47% occurred in the lateral femoral head. Bone apposition was observed in the proximal-medial cortex, around the inferior edge of the implant. Hardly any changes in bone density occurred in the distal neck or the femoral diaphysis. INTERPRETATION: Although resurfacing has produced encouraging clinical results, bone remodelling within the femoral head might be a concern for long-term fixation. Regions of strain concentration at the head-neck junction, which may increase the initial risk of femoral neck fracture, are reduced with bone remodelling. In order to reduce this risk of femoral neck fracture, patients should avoid activities which induce high loading of the hip during the early rehabilitation period after surgery.
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ATP has high- and low-affinity effects on the sodium pump and other P-type ATPases. We have approached this question by using 2',3'-O-(trinitrophenyl)-8-azidoadenosine 5'-diphosphate (TNP-8N(3)-ADP) to photoinactivate and label Na,K-ATPase, both in its native state and after covalent FITC block of its high-affinity ATP site. With the native enzyme, the photoinactivation rate constant increases hyperbolically with a K(D(TNP-8N)3(-)(ADP)) of 0.11 microM; TNP-ATP and ATP protect the site with high affinities. The inactivation does not require Na(+), but K(+) inhibits with a K(K)' of 12 microM; Na(+) reverses this effect, with a K(Na) of 0.17 mM. This pattern suggests that Na(+) and K(+) are binding at sites in their "intracellular" conformation. It was known that FITC did not abolish the reverse phosphorylation by P(i), or the K(+)-phosphatase activity, and that TNP-8N(3)-ADP could subsequently photoinactivate the latter with >100-fold lower affinity; in that case, the cation sites acted as if facing outward [Ward, D. G., and Cavieres, J. D. (1998) J. Biol. Chem. 273, 14277-14284, 33759-33765]. Native and FITC-modified enzymes have now been photolabeled with TNP-8N(3)-[alpha-(32)P]ADP and alpha-chain soluble tryptic peptides separated by reverse-phase HPLC. With native Na,K-ATPase, three labeled peaks lead to the unique sequence alpha-(470)Ile-Val-Glu-Ile-Pro-Phe-Asn-Ser-Thr-Asn-X-Tyr-Gln-Leu-Ser-Ile-His-Lys(487), the dropped residue being alphaLys480. With the FITC enzyme, instead, two independent labeling and purification cycles return the sequence alpha-(721)Ala-Asp-Ile-Gly-Val-Ala-Met-Gly-Ile-Ala-Gly-Ser-Asp-Val-Ser-Lys(736). These results suggest that Na,K-ATPase also has a low-affinity nucleotide binding region, one that is under distinctive allosteric control by Na(+) and K(+). Moreover, the cation effects seem compatible with a slow, passive Na(+)/K(+) carrier behavior of the FITC-modified sodium pump.
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The Supreme Court's ruling upholding Oregon's assisted-suicide law is good news for the rights of physicians, patients and states, and further reinforces the doctor-patient relationship. But physicians working in Oregon hospitals don't expect the decision to affect their operations much. "Very few assisted suicides have occurred in hospitals," says Gwen Dayton, left, of the state hospital association.
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Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS), dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(s)VEGFR-3]). Lymphedema patients were additionally monitored for stage (grade) of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with the mean stage of lymphedema in the doxycycline-treated patients being significantly lower compared to placebo patients 12 mo after treatment. The reduction in the stages manifested as better skin texture, a reduction of deep folds, and fewer deep skin folds. In conclusion, a 6-wk regimen of antifilarial treatment with doxycycline against W. bancrofti showed a strong macrofilaricidal activity and reduction in plasma levels of VEGF-C/sVEGFR-3, the latter being associated with amelioration of supratesticular dilated lymphatic vessels and with an improvement of pathology in lymphatic filariasis patients.
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In states without CON laws, some local governments have been instituting their own control over hospital construction. Now a federal judge has struck down a CON ordinance in Morgan County, Ind., clearing the way for a $40 million hospital expansion project. "This experiment of trying to do (CON) at the local level won't work," says Joseph Chappelle, left, the attorney for Morgan County.