Q-vector measurements: physical examination versus magnetic resonance imaging measurements and their relationship with tibial tubercle-trochlear groove distance.

PURPOSE: An increased lateral quadriceps vector has been associated with lateral patellar dislocation. Surgical correction of this increased vector through tibial tubercle medialization is often recommended when the quadriceps vector is "excessive". This can be evaluated by physical examination measurements of Q-angle and/or tubercle sulcus angle (TSA), as well as the magnetic resonance imaging (MRI) measurement of tibial tubercle-trochlear groove (TT-TG) distance. This study examined the relationship between three objective measurements of lateral quadriceps vector (TT-TG, Q-angle, TSA). A secondary goal was to relate lateral patellar tilt to these measurements. METHODS: Consecutive patients undergoing patellofemoral stabilization surgery from 9/2010 to 6/2011 were included. The Q-angle and TSA were measured on intra-operative physical examination. The TT-TG and patellar tilt were measured on MRI. TSA, Q-angle, and patellar tilt were compared to TT-TG using Pearson correlation coefficient. RESULTS: The study cohort included 49 patients, ages 12-37 (mean 23.2); 62% female. The Pearson correlation coefficients showed (+) significance (p < 0.01) between the TT-TG and both TSA and Q-angle. Tilt and TT-TG were (+) non-significantly correlated. Despite positive correlations of each measurement with TT-TG, there is not uniform intra-patient correlation. In other words, if TT-TG is elevated for a patient, it does not guarantee that all other measurements, including tilt, are elevated in that individual patient. CONCLUSION: The TT-TG distance has significant positive correlation with the measurements of TSA and Q-angle in patients undergoing surgery for patellofemoral instability. The clinical relevance is that the variability within individual patients demonstrates the need for considering both TSA and TT-TG before and during surgical intervention to avoid overcorrection with a medial tibial tubercle osteotomy. LEVEL OF EVIDENCE: Diagnostic study, Level III.

Bone structure and function in male C57BL/6 mice: Effects of a high-fat Western-style diet with or without trace minerals.

PURPOSE: Osteoporosis occurs in both women and men, but most of what we know about the condition comes from studies in females. The present study examined bone structure and function over an 18-month period in male C57BL/6 mice maintained on either a rodent chow diet (AIN76A) or a high-fat, Western-style diet (HFWD). Effects of mineral supplementation were assessed in both diets. METHODS: Trabecular and cortical bone structure in femora and vertebrae were assessed by micro-CT analysis. Following this, bone stiffness and strength measurements were made. Finally, bone levels of several cationic trace elements were quantified, and serum biomarkers of bone metabolism evaluated. RESULTS: Bone loss occurred over time in both diets but was more rapid and extensive in mice on the HFWD. Dietary mineral supplementation reduced bone loss in both diets and increased bone stiffness in the femora and bone stiffness and strength in the vertebrae. Bone content of strontium was increased in response to mineral supplementation in both diets. CONCLUSIONS: Bone loss was more severe in mice on the HFWD and mineral supplementation mitigated the effects of the HFWD. In comparison to previous findings with female C57BL/6 mice, the present studies indicate that males are more sensitive to diet and benefited from a healthy diet (AIN76A), while females lost as much bone on the healthy diet as on the HFWD. Male mice benefited from mineral supplementation, just as females did in the previous study.

Human Radiation Dosimetry for the N-Methyl-D-Aspartate Receptor Radioligand 11C-CNS5161.

UNLABELLED: (11)C-CNS5161 (N-(2-chloro-5-methylthiophenyl)-N'-(3-methylthiophenyl)-N'-(11)C-methylguanidine) has been successfully used in PET imaging of N-methyl-d-aspartate (NMDA) receptors. However, no human dosimetry data have been published. We are planning to use this radiotracer for investigating NMDA receptor function in systemic lupus erythematosus, traumatic brain injury, and Parkinson disease. We have therefore undertaken (11)C-CNS5161 PET imaging to measure the whole-body distribution of this radionuclide and to estimate radiation dose to various organs. METHODS: Dynamic PET studies of the whole body were performed on 5 healthy adults. Regions of interest were drawn over the visualized structures. Resultant time-activity curves were generated and used to determine residence times for dosimetry calculations. S factors were implemented within the OLINDA/EXM software for each structure or organ. RESULTS: For (11)C-CNS5161, organ doses ranged from 0.0002 to 0.0393 mGy/MBq (0.0006-0.1455 rad/mCi). The critical organ for radiation burden was the lungs, with a dose of 0.0393 mGy/MBq (0.1455 rad/mCi). Radiation doses to the reproductive and blood-forming organs were 0.0023, 0.0002, and 0.0020 mGy/MBq (0.0086, 0.0006, and 0.0074 rad/mCi) for the ovaries, testes, and red marrow, respectively. The effective dose equivalent was 0.0106 mSv/MBq (0.0392 rem/mCi). CONCLUSION: The radiation dosimetry for (11)C-CNS5161 for a standard single injection of 555 MBq (15 mCi) will result in an effective dose equivalent of 5.9 mSv (0.59 rem) and a lung dose of 21.8 mGy (2.18 rad) in young, healthy subjects.

Incremental replacement of saturated fats by n-3 fatty acids in high-fat, high-cholesterol diets reduces elevated plasma lipid levels and arterial lipoprotein lipase, macrophages and atherosclerosis in LDLR-/- mice.

OBJECTIVE: Effects of progressive substitution of dietary n-3 fatty acids (FA) for saturated FA (SAT) on modulating risk factors for atherosclerosis have not been fully defined. Our previous reports demonstrate that SAT increased, but n-3 FA decreased, arterial lipoprotein lipase (LpL) levels and arterial LDL-cholesterol deposition early in atherogenesis. We now questioned whether incremental increases in dietary n-3 FA can counteract SAT-induced pro-atherogenic effects in atherosclerosis-prone LDL-receptor knockout (LDLR-/-) mice and have identified contributing mechanisms. METHODS AND RESULTS: Mice were fed chow or high-fat diets enriched in SAT, n-3, or a combination of both SAT and n-3 in ratios of 3:1 (S:n-3 3:1) or 1:1 (S:n-3 1:1). Each diet resulted in the expected changes in fatty acid composition in blood and aorta for each feeding group. SAT-fed mice became hyperlipidemic. By contrast, n-3 inclusion decreased plasma lipid levels, especially cholesterol. Arterial LpL and macrophage levels were increased over 2-fold in SAT-fed mice but these were decreased with incremental replacement with n-3 FA. n-3 FA partial inclusion markedly decreased expression of pro-inflammatory markers (CD68, IL-6, and VCAM-1) in aorta. SAT diets accelerated advanced atherosclerotic lesion development, whereas all n-3 FA-containing diets markedly slowed atherosclerotic progression. CONCLUSION: Mechanisms whereby dietary n-3 FA may improve adverse cardiovascular effects of high-SAT, high-fat diets include improving plasma lipid profiles, increasing amounts of n-3 FA in plasma and the arterial wall. Even low levels of replacement of SAT by n-3 FA effectively reduce arterial lipid deposition by decreasing aortic LpL, macrophages and pro-inflammatory markers.

Preservation of bone structure and function by Lithothamnion sp. derived minerals.

Progressive bone mineral loss and increasing bone fragility are hallmarks of osteoporosis. A combination of minerals isolated from the red marine algae, Lithothamnion sp. was examined for ability to inhibit bone mineral loss in female mice maintained on either a standard rodent chow (control) diet or a high-fat western diet (HFWD) for 5, 12, and 18 months. At each time point, femora were subjected to µ-CT analysis and biomechanical testing. A subset of caudal vertebrae was also analyzed. Following this, individual elements were assessed in bones. Serum levels of the 5b isoform of tartrate-resistant acid phosphatase (TRAP) and procollagen type I propeptide (P1NP) were also measured. Trabecular bone loss occurred in both diets (evident as early as 5 months). Cortical bone increased through month 5 and then declined. Cortical bone loss was primarily in mice on the HFWD. Inclusion of the minerals in the diet reduced bone mineral loss in both diets and improved bone strength. Bone mineral density was also enhanced by these minerals. Of several cationic minerals known to be important to bone health, only strontium was significantly increased in bone tissue from animals fed the mineral diets, but the increase was large (5-10 fold). Serum levels of TRAP were consistently higher in mice receiving the minerals, but levels of P1NP were not. These data suggest that trace minerals derived from marine red algae may be used to prevent progressive bone mineral loss in conjunction with calcium. Mineral supplementation could find use as part of an osteoporosis-prevention strategy.

Synthesis and evaluation of hermitamides A and B as human voltage-gated sodium channel blockers.

Hermitamides A and B are lipopeptides isolated from a Papau New Guinea collection of the marine cyanobacterium Lyngbya majuscula. We hypothesized that the hermitamides are ligands for the human voltage-gated sodium channel (hNa(V)) based on their structural similarity to the jamaicamides. Herein, we describe the nonracemic total synthesis of hermitamides A and B and their epimers. We report the ability of the hermitamides to displace [(3)H]-BTX at 10 µM more potently than phenytoin, a clinically used sodium channel blocker. We also present a potential binding mode for (S)-hermitamide B in the BTX-binding site and electrophysiology showing that these compounds are potent blockers of the hNav1.2 voltage-gated sodium channel.

Synthesis of (S)-jamaicamide C carboxylic acid.

The jamaicamides are natural product sodium channel blockers derived from the cyanobacterium Lyngbya majuscula. The carboxylic acid fragment of jamaicamide C contains a methyl stereocenter and a trisubstituted E chloroolefin. Herein, we present the nonracemic synthesis of the aliphatic chain of jamaicamide C. The methyl stereocenter was installed using Evans' oxazolidinone methodology, and the trisubstituted chloroolefin was set by silylstannylation of a triple bond.

Avoidance of complications in older patients and Medicare recipients undergoing gastric bypass.

HYPOTHESIS: Perioperative morbidity and mortality do not increase in carefully evaluated and managed Medicare and elderly patients undergoing gastric bypass. DESIGN: Retrospective review of a prospectively maintained bariatric database. SETTING: Academic tertiary care medical center. PATIENTS: We reviewed our database of 928 consecutive patients who underwent gastric bypass from March 24, 1998, through May 31, 2006. Of these patients, 36 underwent revision surgery and were excluded. The remaining 892 patients were separated into 4 groups by age and Medicare status. Group 1 consisted of 46 patients 60 years or older at the time of gastric bypass (range, 60-66 years). Group 2 consisted of 846 patients 59 years or younger at the time of gastric bypass (range, 18-59 years). Group 3 consisted of 31 Medicare recipients (age range, 31-66 years). Group 4 consisted of 861 non-Medicare recipients (age range, 18-64 years). MAIN OUTCOME MEASURES: Groups were compared in terms of demographics, morbidity, and mortality. RESULTS: No differences were found in outcomes between older vs younger and Medicare vs non-Medicare patients for any postoperative complication or mortality. CONCLUSIONS: Bariatric surgery can be performed in carefully selected Medicare recipients and patients 60 years or older with acceptable morbidity and mortality. No difference was found in the occurrence of complications in Medicare patients, patients younger than 60 years, or patients 60 years and older. We believe that these results reflect careful patient selection, intensive preoperative education, and expert operative and perioperative management. Our results indicate that bariatric surgery should not be denied solely based on age or Medicare status.