Correction to: Differences in bone quality and strength between Asian and Caucasian young men.

The second name of the ninth author, X.E. Guo, was incorrectly coded as part of his surname. The publisher apologises for the inconvenience caused.

Differences in bone quality and strength between Asian and Caucasian young men.

This is a cross-sectional study to assess differences in bone quality in young Asian and Caucasian (n = 30/group) men between 25 and 35 years. We found that Asians had smaller bones, thicker and denser cortices, and more plate-like trabeculae, but stiffness did not differ between groups. INTRODUCTION: We conducted a cross-sectional study to assess differences in bone quality in young Asian and Caucasian (n = 30/group) men between 25 and 35 years. METHODS: We measured bone mineral density (BMD) at the spine, total hip (TH), femoral neck (FN), and forearm by dual energy X-ray absorptiometry (DXA), and bone geometry, density, microarchitecture, and mechanical competence at the radius and tibia by high-resolution peripheral quantitative computed tomography (HR-pQCT) with application of individual trabecula segmentation (ITS) and trabecular and whole bone finite element analysis (FEA). We measured load-to-strength ratio to account for differences in bone size and height, respectively. We used Wilcoxon rank sum and generalized linear models adjusted for height, weight, and their interaction for comparisons. RESULTS: Asians were 3.9 % shorter and weighed 6.5 % less than Caucasians. In adjusted models: by DXA, there were no significant race-based differences in areal BMD; by HR-pQCT, at the radius, Asians had smaller total and trabecular area (p = 0.003 for both), and denser (p = 0.01) and thicker (p = 0.04) cortices at the radius; by ITS, at the radius Asians, had more plate-like than rod-like trabeculae (PR ratio p = 0.01), greater plate trabecular surface (p = 0.009) and longer rod length (p = 0.002). There were no significant race-based differences in FEA or the load-to-strength ratio. CONCLUSIONS: Asians had smaller bones, thicker and denser cortices, and more plate-like trabeculae, but biomechanical estimates of bone strength did not differ between groups. Studies are needed to determine whether these differences persist later in life.

Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects.

Mirtazapine and olanzapine are easy-to-use psychiatric drugs with potent antinausea effects. Ondansetron and later members of the 'setron class are currently standard treatments for cancer chemotherapy-related nausea and emesis. They are potent 5-HT3 blockers, but it is often not appreciated that mirtazapine and olanzapine bind with similar affinity to 5-HT3 receptors, have a longer half-life, are considerably cheaper than the 'setron class, and often offer better and smoother 24-h nausea control than 'setron class drugs. Mirtazapine and olanzapine often have salutary antianxiety effects and improve sleep quality. They occasionally relieve chemotherapy-related and advanced cancer-related nausea and appetite decrease better than the 'setron group that are specifically marketed for nausea control. Mirtazapine and olanzapine frequently give potent nausea reduction and appetite increase in advanced cancer-related cachexia. Several cytokine changes potentially induced by mirtazapine and olanzapine use are discussed that may have salutary effects in several cancers. We suggest mirtazapine and olanzapine be included as first-line options in treating both chemotherapy- and advanced cancer-related nausea. Multiple clinical and economic advantages of mirtazapine and olanzapine over currently used 'setron class medicines are reviewed. Double-blind studies against the 'setron class drugs are warranted.

Doxorubicin cardiomyopathy via TLR-2 stimulation: potential for prevention using current anti-retroviral inhibitors such as ritonavir and nelfinavir.

Doxorubicin remains a useful anti-cancer drug but as lifetime dose approaches 500 mg/m2 and particularly when this dose is exceeded, iatrogenic life-threatening cardiomyopathy becomes progressively more likely. This note reviews evidence indicating that doxorubicin induced cardiomyopathy is partly mediated by stimulation of Toll-like receptors (TLR) 2 and 4 which are expressed on cardiomyocytes. Indinavir, nelfinavir, ritonavir, and saquinavir are currently marketed protease inhibitors used to suppress human immunodeficiency virus. They have recently been shown to inhibit signalling at TLR 2 and 4 as well as intracellular events downstream from these receptors. It is possible that these FDA-approved anti-retroviral protease inhibitors could be used off-label to diminish likelihood of doxorubicin cardiotoxicity permitting higher doxorubicin doses. We suggest that currently marketed anti-viral protease inhibitors be investigated in animal models of doxorubicin cardiomyopathy and if such studies do indeed show protection, human studies be initiated.

Serotonin transporter function and expression are reduced in mice with TNBS-induced colitis.

Regulated release of serotonin (5-HT) from enterochromaffin (EC) cells activates neural reflexes that are involved in gut motility, secretion, vascular perfusion and sensation. The 5-HT-selective reuptake transporter (SERT) terminates serotonergic signalling in the intestinal mucosa. The aim of this investigation was to determine whether mucosal 5-HT content, release, and/or reuptake are altered in a murine model of immune cell-mediated colitis. Experiments were conducted 6 days after colitis was induced by 2,4,6-trinitrobenzene sulfonic acid, a time point when macroscopic and histological damage scores indicated significant inflammation. During inflammation, SERT transcript levels and immunoreactivity were reduced, and the uptake of [3H] 5-HT was impaired. Increases in mucosal 5-HT content and the number of 5-HT-immunoreactive mast cells in the lamina propria were also detected in the inflamed region, whereas EC cell numbers did not change. Mucosal 5-HT released under basal and stimulated conditions was unchanged in animals with colitis. These data suggest that murine colitis alters 5-HT signalling by increasing 5-HT availability through decreased 5-HT uptake by mucosal epithelial cells. These findings support the concept that altered 5-HT signalling could be a contributing factor in altered gut function and sensitivity in inflammatory bowel disease.

Stereospecific inhibition of monoamine uptake transporters by meta-hydroxyephedrine isomers.

Meta-hydroxyephedrine (HED) comprises four stereoisomers consisting of two enantiomeric pairs related to ephedrine and pseudoephedrine. HED is transported into adrenergic neurons and radiolabeled HED has been employed in positron emission tomography (PET) to image adrenergic neurons in vivo. To extend structure-activity analyses of binding sites within monoamine transporters and to determine which stereoisomer displayed the best selectivity for PET imaging applications, we tested the HED compounds for their abilities to inhibit [(3)H]neurotransmitter uptake into platelets, transfected cells, and chromaffin vesicles. We hypothesized that the HED compounds would be most potent at the norepinephrine transporter (NET) compared to the serotonin or dopamine transporters and that the 1R diastereomers would be more effective than 1S diastereomers. Supporting the hypotheses, all stereoisomers were most potent at the NET and the 1R,2S stereoisomer was the most potent inhibitor overall. However, the 1S,2R isomer may be preferred for PET applications because of better selectivity among the transporters and reduced neuronal recycling.

Placement of pedicle screws in the human cadaveric cervical spine: comparative accuracy of three techniques.

STUDY DESIGN: This investigation was conducted in two parts. In the first part, a morphometric analysis of critical cervical pedicle dimensions were measured to create guidelines for cervical pedicle screw fixation based on posterior cervical topography. In the second part of the study, a human cadaver model was used to assess the accuracy and safety of transpedicular screw placement in the subaxial spine using three different surgical techniques: 1) using surface landmarks established in the first part of the study, 2) using supplemental visual and tactile cues provided by performing laminoforaminotomies, and 3) using a computer-assisted surgical guidance system. OBJECTIVE: To assess the accuracy of transpedicular screw placement in the cervical spine using three surgical techniques. SUMMARY OF BACKGROUND DATA: A three-column fixation device implanted to secure an unstable cervical spine can be a valuable tool with a biomechanical advantage in the spine surgeon's armamentarium. Despite this advantage, concerns over surgical neurovascular complications have surfaced. Cadaver-based morphometric measurements used to guide the surgeon in the placement of a pedicle screw show significant variability, raising legitimate concerns as to whether transpedicular fixation can be applied safely. METHODS: Precise measurements of 14 human cadaveric cervical spines were made by two independent examiners of pedicle dimensions, angulation, and offset relative to the lateral mass boundaries. On the basis of this analysis, guidelines for pedicle screw placement relative to posterior cervical topography were derived. In the second part of the study, 12 human cadaveric cervical spines were instrumented with 3.5-mm screws placed in the pedicles C3-C7 according to one of three techniques. Cortical integrity and neurovascular injury were then assessed by obtaining postoperative computed tomography scans (1-mm cuts) of each specimen. Cortical breaches were classified into critical or noncritical breaches. RESULTS: Linear measurements of pedicle dimensions had a wide range of values with only fair interobservercorrelation. Angular measurements showed similarangulation in the transverse plane (40 degrees ) at each level. With respect to the sagittal plane, both C3 and C4 pedicles were oriented superiorly relative to the axis of the lateral mass, whereas the C6 and C7 pedicles were oriented inferiorly. The dorsal entry point of the pedicle on the lateral mass defined by transverse and sagittal offset had similar mean values with wide ranges, although there often was excellent correlation between observers. There were no significant interlevel, right/left, or male/female differences noted with respect to offset. Using one of three techniques, 120 pedicles were instrumented. In group 1 (morphometric data): 12.5% of the screws were placed entirely within the pedicle; 21.9% had a noncritical breach; and 65. 5% had a critical breach. In group 2 (laminoforaminotomy), 45% of the screws were within the pedicle; 15.4% had a noncritical breach; and 39.6% had a critical breach. In group 3 (computer-assisted surgical guidance system), 76% of the screws were entirely within the pedicle; 13.4% had a noncritical breach; and 10.6% had a critical breach. Regardless of the technique used, the vertebral artery was the structure most likely to be injured. CONCLUSIONS: On the basis of the morphometric data, guidelines for cervical spine pedicle screw placement at each subaxial level were derived. Although a statistical analysis of cadaveric morphometric data obtained from the cervical spine could provide guidelines for transpedicular screw placement based on topographic landmarks, sufficient variation exists to preclude safe instrumentation without additional anatomic data. Insufficient correlation between different surgeons' assessments of surface landmarks attests to the inadequacy of screw insertion techniques in the cervical spine based on such specific topographic guide