Fracture repair during external fixation: Torsion tests of rabbit osteotomies

Bone repair was studied in the rabbit tibiofibular bone after a midshaft transverse osteotomy stabilized by external fixation and heavy compression. Both subendosteal and subperiosteal callus formation with concomitant contact healing were observed within 3 weeks, and were further succeeded by subendosteal resorption and increased porosis resulting in atrophy of the cortical bone. Subjected to the torsion test, the bones exhibited restoration of strength within 3 weeks, with maximal energy absorption and elasticity at 6 weeks. The failure of the osteotomy in the torsion test, with radiographic visibility of the osteotomy, characterized the soft-tissue type of behavior of the bones. Hard-tissue like behaviour of the bones with resistance to torsion at the osteotomy site and radiographic obliteration of the osteotomy line occurred by 12 weeks, indicating complete union of the osteotomy. Our experiments demonstrate that elastic external fixation is preferable to the rigid compression plate.     

A double blind placebo controlled trial of the calcium entry blocking drug, nicardipine, in the treatment of vasospasm following severe head injury

A double blind, placebo controlled trial of nicardipine in the treatment of high Doppler Flow Velocity (DFV) following severe head injury (Glasgow Coma Score (GSC) less than or equal to 8) was performed. Thirty patients with high DFV (greater than or equal to 100 cm/s for 6 h duration) on transcranial Doppler ultrasound, were treated with nicardipine or placebo for 24 h (2.5 mg/h, increasing in steps of 2.5 mg/h at 2 h intervals (maximum rate 7.5 mg/h) depending on response of DFV). DFV was measured hourly for 24 h and then every 12 h for 2 days. Nicardipine significantly reduced DFV below the threshold of 100 cm/s (16/19 cf placebo 3/11, chi-square p less than 0.001). In the nicardipine treated group maximum DFV was significantly reduced (p less than 0.001) and time with DFV below 100 was significantly longer. Rises in DFV were significantly reduced by the drug if the DFV was normal at the time of entry. High DFV returned on cessation of the infusion. No unexpected or adverse side effects were seen. No clinical benefit was demonstrable.     

Permanent Cardiac Pacing in Octogenarians

A significant percentage of patients in need of a permanent pacemaker are older than 80 years. The implantation policy may be determined either by the patient's physical activity or by chronologic age. The trend in pacemaker implantation in patients over 80 during the last 10 years in our institution was evaluated and compared with the trend in the patients younger than 80 at the time of implantation. Of 519 patients who had primary pacemaker implantation, 152 (29%) were older than 80 at the time of the procedure. Another 189 patients had second implantation procedures, and 80% of them were older than 80 years. Complete atrioventricular block was the indication for pacing in 44 ?+/- 11% and sick sinus syndrome in 25 ?+/- 7%. The tendency to implant dual-chamber pacemakers increased from 0% during 1985 to 76% in 1994, including 69% DDD and 31% DDDR, but the transition was faster in the younger group. By 1994, there was no difference in the incidence of advanced pacing systems in the 2 age groups. During 1985, only VVI pacemakers were replaced, and during 1994, less than 10% were replaced with simple ventricular pacing units. Pacing system upgrading was frequent during the second half of the decade. The success and complication rate of implantation did not differ in the 2 groups.     

In the Shadow of Hemagglutinin: A Growing Interest in Influenza Viral Neuraminidase and Its Role as a Vaccine Antigen

Despite the availability of vaccine prophylaxis and antiviral therapeutics, the influenza virus continues to have a significant, annual impact on the morbidity and mortality of human beings, highlighting the continued need for research in the field. Current vaccine strategies predominantly focus on raising a humoral response against hemagglutinin (HA)—the more abundant, immunodominant glycoprotein on the surface of the influenza virus. In fact, anti-HA antibodies are often neutralizing, and are used routinely to assess vaccine immunogenicity. Neuraminidase (NA), the other major glycoprotein on the surface of the influenza virus, has historically served as the target for antiviral drug therapy and is much less studied in the context of humoral immunity. Yet, the quest to discern the exact importance of NA-based protection is decades old. Also, while antibodies against the NA glycoprotein fail to prevent infection of the influenza virus, anti-NA immunity has been shown to lessen the severity of disease, decrease viral lung titers in animal models, and reduce viral shedding. Growing evidence is intimating the possible gains of including the NA antigen in vaccine design, such as expanded strain coverage and increased overall immunogenicity of the vaccine. After giving a tour of general influenza virology, this review aims to discuss the influenza A virus neuraminidase while focusing on both the historical and present literature on the use of NA as a possible vaccine antigen.     

Importance of delaying balloon angioplasty in patients with unstable angina pectoris

Angioplasty in patients with unstable coronary artery disease is associated with higher complication rates compared with patients with stable disease. In this report we describe our results from a group of patients with unstable disease (unstable angina pectoris and postmyocardial infarction) where a strategy of delaying angioplasty for >5 days after admission was undertaken. Included are 2069 consecutive patients: 1197 treated for stable angina pectoris and 872 treated during admission for unstable angina or myocardial infarction. There was no difference between the two groups in angioplasty success (92.1% stable, 92.3% unstable), failure to dilate without complication (6.4% stable, 6.1 % unstable), or in the rate of major complications: death (0.5% stable, 1.1% unstable), Q-wave myocardial infarction (0.9% stable, 1.1% unstable), and emergency coronary artery bypass (0.6% stable, 0.3% unstable). The duration of hospitalization following angioplasty was longer in the unstable group (5.6 ± 8.1 days vs. 4.2 ± 4.1 days; p < 0.001) because of longer duration of hep-arin infusion. There was no difference between groups in minor complications such as groin hematoma and pseudoa-neurysm, renal failure, or infections. It was concluded that delaying angioplasty in unstable patients for > 5 days after admission is a safe and effective therapeutic strategy for this group of patients. The need for prolonged heparin infusion after angioplasty is increased in unstable patients and thus the duration of hospitalization after the procedure is longer.     

Sites of proteolytic processing and noncovalent association of the distal C-terminal domain of CaV1.1 channels in skeletal muscle

In skeletal muscle cells, voltage-dependent potentiation of Ca2+ channel activity requires phosphorylation by cAMP-dependent protein kinase (PKA) anchored via an A-kinase anchoring protein (AKAP15), and the most rapid sites of phosphorylation are located in the C-terminal domain. Surprisingly, the site of interaction of the complex of PKA and AKAP15 with the alpha1-subunit of Ca(V)1.1 channels lies in the distal C terminus, which is cleaved from the remainder of the channel by in vivo proteolytic processing. Here we report that the distal C terminus is noncovalently associated with the remainder of the channel via an interaction with a site in the proximal C-terminal domain when expressed as a separate protein in mammalian nonmuscle cells. Deletion mapping of the C terminus of the alpha1-subunit using the yeast two-hybrid assay revealed that a distal C-terminal peptide containing amino acids 1802-1841 specifically interacts with a region in the proximal C terminus containing amino acid residues 1556-1612. Analysis of the purified alpha1-subunit of Ca(V)1.1 channels from skeletal muscle by saturation sequencing of the intracellular peptides by tandem mass spectrometry identified the site of proteolytic processing as alanine 1664. Our results support the conclusion that a noncovalently associated complex of the alpha1-subunit truncated at A1664 with the proteolytically cleaved distal C-terminal domain, AKAP15, and PKA is the primary physiological form of Ca(V)1.1 channels in skeletal muscle cells.     

LC-MS/MS测定人血浆中对乙酰氨基酚及其人体药动学和生物等效性研究

目的 建立一种快速、灵敏的高效液相色谱-串联质谱（HPLC-MS/MS）方法以测定人血浆中对乙酰氨基酚浓度,并应用于两种对乙酰氨基酚制剂的人体药代动力学和生物等效性研究。方法 以替硝唑为内标,200μL血浆样品经5倍于其体积的乙酸乙酯液液萃取,再经Waters XBridge? C18柱等度洗脱分离后导入串联质谱,以正离子多反应监测模式进行定量分析,对乙酰氨基酚和内标的选择性反应离子对分别是m/z 152→110和248→121。方法经验证后应用于19名健康受试者单剂量空腹口服两种对乙酰氨基酚制剂500mg后药代动力学和生物等效性的研究。结果 血浆中对乙酰氨基酚在0.1～8.0 μg·mL-1范围内线性良好（r2 > 0.99）,最低检测限为 0.1 μg·mL-1,提取回收率为91.0%～98.7%,日内和日间准确度分别为98.8%～111.3% （精密度：CV ? 9.03%）和94.9%～102.6% （精密度：CV ? 10.68%）。生物等效性试验中,受试制剂与参比制剂的主要药代动力学参数Cmax、AUC0-t和AUC0-∞ 几何均值比的90%置信区间分别为83.50%～105.79%,94.25%～101.54%和93.24%～101.02%,均落在生物等效可接受标准80.00%～125.00%范围内。结论 所建立测定人血浆中对乙酰氨基酚浓度的HPLC-MS/MS法具有快速灵敏、回收率高、选择性好的特点,适用于对乙酰氨基酚片人体药代动力学和生物等效性研究。受试制剂与参比制剂在人体内吸收速度和程度相似,两种制剂生物等效。     

Tumor necrosis factor and interleukin-6 levels in hypertensive patients with and without left ventricular hypertrophy

The objective of this prospective study was to examine the association between serum levels of TNF (tumor-necrosis factor) and IL-6 (interleukin-6) and left ventricular mass in hypertensive patients. Hypertensive patients currently receiving medical therapy were eligible. All subjects underwent echocardiography with measurements of left ventricular (LV) mass and ejection fraction (EF) and had serum levels of TNF and IL-6 measured by ELISA immunoassay. 35 subjects (20F, 15M; mean age 56.4 +/- 10.5 yrs) were studied. 19 patients (54%) had elevated LV mass. Of these patients, 6 (32%) had detectable serum TNF levels and 1 (7%) had detectable IL-6 levels, (p = NS). Hypertensive patients with elevated LV mass do not consistently exhibit elevated cytokine levels when compared to those with normal LV mass.