Genome-wide scan identified QTLs underlying femoral neck cross-sectional geometry that are novel studied risk factors of osteoporosis.

A genome-wide screen was conducted using a large white sample to identify QTLs for FNCS geometry. We found significant linkage of FNCS parameters to 20q12 and Xq25, plus significant epistatic interactions and sex-specific QTLs influencing FNCS geometry variation. INTRODUCTION: Bone geometry, a highly heritable trait, is a critical component of bone strength that significantly determines osteoporotic fracture risk. Specifically, femoral neck cross-sectional (FNCS) geometry is significantly associated with hip fracture risk as well as genetic factors. However, genetic research in this respect is still in its infancy. MATERIALS AND METHODS: To identify the underlying genomic regions influencing FNCS variables, we performed a remarkably large-scale whole genome linkage scan involving 3998 individuals from 434 pedigrees for four FNCS geometry parameters, namely buckling ratio (BR), cross-sectional area (CSA), cortical thickness (CT), and section modulus (Z). The major statistical approach adopted is the variance component method implemented in SOLAR. RESULTS: Significant linkage evidence (threshold LOD = 3.72 after correction for tests of multiple phenotypes) was found in the regions of 20q12 and Xq25 for CT (LOD = 4.28 and 3.90, respectively). We also identified eight suggestive linkage signals (threshold LOD = 2.31 after correction for multiple tests) for the respective geometry traits. The above findings were supported by principal component linkage analysis. Of them, 20q12 was of particular interest because it was linked to multiple FNCS geometry traits and significantly interacted with five other genomic loci to influence CSA variation. The effects of 20q12 on FNCS geometry were present in both male and female subgroups. Subgroup analysis also revealed the presence of sex-specific quantitative trait loci (QTLs) for FNCS traits in the regions such as 2p14, 3q26, 7q21 and 15q21. CONCLUSIONS: Our findings laid a foundation for further replication and fine-mapping studies as well as for positional and functional candidate gene studies, aiming at eventually finding the causal genetic variants and hidden mechanisms concerning FNCS geometry variation and the associated hip fractures.     

Accuracy of magnetic resonance imaging compared to computerized tomography and renal selective angiography in preoperatively staging renal cell carcinoma.

During 1986 and 1987, 47 patients with renal cell carcinoma were evaluated preoperatively with CT, angiography and MRI. The preoperative tumor stage (T), lymph node metastases and venous involvement determined with the three methods were compared to the operative and histopathological findings. For T stage, angiography proved less accurate (54%) than CT (64%) or MRI (63%). MRI was found to be superior to CT in assessing lymph nodes, with an overall accuracy of 89% and sensitivity of 100% compared to 77 and 60%, respectively, of CT. For venous involvement CT was overall more accurate (74%) than angiography (65%) or MRI (63%). All three methods expressed a low sensitivity (between 31 and 41%) and a high specificity (between 95 and 100%) for detecting venous involvement. The minimal advantages of MRI compared to its high cost do not justify its routine use. CT remains the method of choice in staging preoperatively renal cell carcinoma.     

A specific enhanced recovery protocol decreases opioid use after thyroid and parathyroid surgery

BackgroundEnhanced recovery protocols have not been investigated previously for cervical endocrine surgery. The study aim was to determine whether systematic implementation of an enhanced recovery protocol specific for thyroid/parathyroid surgery can improve postoperative outcomes.MethodsA customized enhanced recovery protocol for thyroid/parathyroid surgery was designed and utilized systematically for all patients who underwent parathyroidectomy, thyroid lobectomy, or total thyroidectomy. Outcomes were assessed 12 months before enhanced recovery protocol implementation (n = 464 patients) and after enhanced recovery protocol implementation (n = 654 patients).ResultsEnhanced recovery protocol implementation was associated with a 72% decrease in mean oral morphine equivalents utilized in-house (before 82 ± 64 versus after 23 ± 28; P < .0001) and many enhanced recovery protocol patients were entirely opioid-free (0.2% vs 21%, P < .0001). When used, the enhanced recovery protocol was associated with a lesser mean amount of ondansetron to treat postoperative nausea and vomiting (5.5 mg ± 3 vs 4.5 ± 2: P < .0001). Duration of stay was short before implementation of the enhanced recovery protocol and did not change substantially after implementation (1.1 days ± 0.7 vs 1.1 ± 0.7; P = .26).ConclusionThe systematic use of a simple, cervical, endocrine surgery-specific enhanced recovery protocol decreased perioperative opioid use by ~70%, with significantly less postoperative nausea and vomiting. Implementation of a multidisciplinary enhanced recovery protocol may be an important initial step toward limiting opioid overuse during common operative procedures.     

"QT" pacemaker in aggregate exchange. Do old electrodes impair functional ability?

A "QT"-interval driven rate responsive pacemaker can also be implanted on the occasion of pacemaker replacement. To evaluate the electrophysiological properties and limitations of chronic leads, in 30 patients the evoked intracardiac electrogram was recorded via the chronic lead during pacemaker replacement (14 different types, mean interval after implantation 111 (25-171 months). T-wave detectability was evaluated with different pulse amplitudes (2.5 and 5.0 V) and two pacemaker systems (TX 915, Rhythmyx) with different "fast recharge" mechanisms. In particular, the T-wave signal was influenced by capacitor discharge effects. At 2.5 V output T-wave amplitude was greater than or equal to 1.5 mV in all (19) patients, who could be paced at this voltage. However, at 5 V in 9/30 patients T-wave was less than 1 mV and detection was not possible in 6/30 cases. During pacing with the newly developed "QT"-interval driven, rate-responsive pacemaker (Rhythmyx) with two fast recharge pulses, in nine investigated patients the T-wave was markedly better discriminable compared to the TX 915 pacemaker. Accordingly, in 37 patients with implanted "QT"-controlled pacemakers (TX 911): n = 13; TX 915: n = 21; Rhythmyx: n = 3. Indication for pacemaker therapy: high degree AV block: n = 24, sick-sinus syndrome: n = 13) reliable T-wave sensing was possible at 2.5 V/0.2 ms output, whereas at 5 V/2 ms no T-wave sensing could be achieved in 8/37 cases. On the occasion of pacemaker replacement the "QT"-controlled pacemaker can be implanted without intraoperative measurements, whenever a pulse amplitude less than 2.5 V is sufficient for stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetic Variations in Bone Density, Histomorphometry, and Strength in Mice

The purpose of this study was to assess breed-related differences in bone histomorphometry, bone biomechanics, and serum biochemistry in three mouse breeds shown to differ in bone mineral density (BMD) (as measured by DXA) and bone mineral content (BMC). Femurs, tibiae, and sera were collected from 16-week-old C3H/HeJ {C3H}, C57BL/6J {BL6}, and DBA/2J {DBA}mice (n = 12/breed). Data collected included BMC and BMD (femora), histomorphometry of cancellous (distal femur) and cortical bone (diaphyseal tibiae and femora), bone strength (femora), and serum alkaline phosphatase (ALP). Consistent with previous reports, BMC and BMD were higher in C3H than in BL6 or DBA mice. The higher BMD in the C3H breed was associated with greater cancellous bone volume, cortical bone area, periosteal bone formation rate, biomechanical strength, and serum ALP. However, mid-diaphyseal total femoral and tibial cross-sectional area and moment of inertia were greatest in BL6, intermediate in C3H, and lowest in DBA mice. The specific distribution of cortical bone in C3H, BL6, DBA mice represents a difference in adaptive response to similar mechanical loads in these breeds. This difference in adaptive response may be intrinsic to the adaptive mechanism, or may be intrinsic to the bone tissue material properties. In either case, the bone-adaptive response to ordinary mechanical loads in the BL6 mice yields bones of lower mechanical efficiency (less stiffness per unit mass of bone tissue) and does not adapt as well as that of the C3H mice where the final product is a bone with greater resistance to bending under load. We suggest that the size, shape, and BMD of the bone are a result of breed-specific genetically regulated cellular mechanisms. Compared with the C3H mice, the lower BMD in BL6 mice is associated with long bones that are weaker because the larger cross-sectional area fails to compensate completely for their lower BMD and BMC. Received: 16 November 1999 / Accepted: 19 April 2000 / Online publication: 27 July 2000     

妥卡尼对豚鼠心室肌细胞钙电流和钾电流的抑制作用

利用酶分散的成年豚鼠心室肌细胞和全细胞电压钳技术,研究了妥卡尼(tocainide)对心室肌细胞钙电流(I_ca)、延迟整流钾电流(I_k)和ATP敏感性钾电流(Ik,ATP)的作用。结果表明,妥卡尼对I_ca和I_k均显示浓度相关的抑制作用,妥卡尼50umol·L^-1对I_ca和I_k的抑制率分别为16%和3%。这可能是妥卡尼有效抑制室上性心动过速和缩短心肌动作电位平台期的重要机制。     

A new heparin fragment decreases liver ischemia-reperfusion injury

<正>To the Editor:Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure.Intracellular calcium overload is associated to cellular death during ischemiareperfusion.A recently discovered heparin fragment (HF),trisulfated disaccharide (TD),that acts on sodium-calcium exchanger(NCX) decreasing intracellular Ca²⁺,showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1],