体外制成复合软质再生颅骨修复材料填充犬颅骨缺损

目的:目前颅骨修补材料有很多种,但都为异源性无机骨替代物,并且应用该方法又要给患者再次行开颅手术,实验拟开展新型颅骨再生材料的研究。方法:实验于2006-05/11在解放军第一五七医院动物中心及中山大学附属第三医院动物实验室完成。①实验动物:30只犬随机分为实验组20只,对照组10只。②实验方法:应用纳米级羟基磷灰石为支架和成骨细胞培养,加入脱矿的犬类骨基质为载体的重组人类骨形成蛋白2,制成复合软质再生颅骨。实验组犬在右侧颅骨缺损中填补藻酸钙凝胶、成骨细胞、纳米级骨粉的复合材料,左侧颅骨缺损中填补藻酸钙凝胶、成骨细胞、纳米级骨粉和重组人类骨形成蛋白2的复合材料。对照组犬在右侧为单纯颅骨缺损,左侧颅骨缺损中填补藻酸钙凝胶、成骨细胞、纳米级骨粉和重组人类骨形成蛋白2复合材料。实验过程中对动物处置符合动物伦理学标准。③实验评估:手术后1,2,3,6个月X射线片检查颅骨缺损修复情况,对再生的颅骨组织标本进行茜素红S染色,观察成骨能力及再生材料骨膜组织细胞体外培养情况。结果:实验动物均进入结果分析。术后1个月,成骨活跃,骨端新生骨小梁基本覆盖骨断端,缺损区可见较多新生骨小梁形成,骨端新生骨小梁向缺损区长入;术后2个月可见较多散在骨岛形成;术后3个月可见成熟骨,并有髓腔形成,缺损区大量新骨形成。而各对照组骨断端处有散在骨岛,或被增生的纤维结缔组织占据,可见大量纤维组织及毛细血管长入,植入的基质材料基本被吸收,无新骨生成。结论:应用纳米级羟基磷灰石为支架和成骨细胞培养,加入脱矿骨基质为载体的重组人类骨形成蛋白2,制成的复合软质再生颅骨能自身代谢并逐渐骨化,形成新的颅骨。     

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

Ten-year follow up after laparoscopic Nissen fundoplication for gastroesophageal reflux disease

Laparoscopic Nissen fundoplication was first undertaken in the early 1990s. Appreciable numbers of patients with 10-year follow up are only now available. This study assesses long-term outcome and durability of outcome after laparoscopic Nissen fundoplication for treatment of gastro-esophageal reflux disease. Since 1991, 829 patients have undergone laparoscopic fundoplications and are prospectively followed. Two hundred thirty-nine patients, 44 per cent male, with a median age of 53 years (+/- 15 standard deviation) underwent laparoscopic Nissen fundoplications at least 10 years ago; 28 (12%) patients were "redo" fundoplications. Before and after fundoplication, among many symptoms, patients scored the frequency and severity of dysphagia, chest pain, vomiting, regurgitation, choking, and heartburn using a Likert scale (0 = never/not bothersome to 10 = always/very bothersome). Symptom scores before versus after fundoplication were compared using a Wilcoxon matched-pairs test. Data are reported as median, mean +/- standard deviation, when appropriate. After fundoplication, length of stay was 2 days, 3 days +/- 4.8. Intra-operative inadvertent events were uncommon and without sequela: 1 esophagotomy, 1 gastrotomy, 3 cardiac dysrhythmias, and 3 CO2 pneumothoraces. Complications after fundoplication included: 1 postpneumonic empyema, 3 urinary retentions, 2 superficial wound infections, 1 urinary tract infection, 1 ileus, and 1 intraabdominal abscess. There were two perioperative deaths; 88 per cent of the patients are still alive. After laparoscopic Nissen fundoplication, frequency and severity scores dramatically improved for all symptoms queried (P < 0.001), especially for heartburn frequency (8, 8 +/- 3.2 versus 2, 3 +/- 2.8, P < 0.001) and severity (10, 8 +/- 2.9 versus 1, 2 +/- 2.5, P < 0.001). Eighty per cent of patients rate their symptoms as almost completely resolved or greatly improved, and 85 per cent note they would again have the laparoscopic fundoplication as a result of analysis of our initial experience, thereby promoting superior outcomes in the future. Nonetheless, follow up at 10 years and beyond of our initial experience documents that laparoscopic fundoplication durably provides high patient satisfaction resulting from long-term amelioration of the frequency and severity of symptoms of gastroesophageal reflux disease. These results promote further application of laparoscopic Nissen fundoplication.     

Simvastatin protects against cholestasis-induced liver injury

Background:

Bile duct obstruction is associated with hepatic accumulation of leukocytes and liver injury. The aim of this study was to evaluate the effect of simvastatin on cholestasis-induced liver inflammation and tissue damage.

Experimental approach:

C57BL/6 mice were treated with simvastatin (0.02 and 0.2 mg·kg⁻¹) and vehicle before and after undergoing bile duct ligation (BDL) for 12 h. Leukocyte recruitment and microvascular perfusion in the liver were analysed using intravital fluorescence microscopy. CXC chemokines in the liver were determined by enzyme-linked immunosorbent assay. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatic levels of myeloperoxidase (MPO) were also determined.

Key results:

Administration of 0.2 mg·kg⁻¹ simvastatin decreased ALT and AST by 87% and 83%, respectively, in BDL mice. This dose of simvastatin reduced hepatic formation of CXC chemokines by 37–82% and restored sinusoidal perfusion in cholestatic animals. Moreover, BDL-induced leukocyte adhesion in sinusoids and postsinusoidal venules, as well as MPO levels in the liver, was significantly reduced by simvastatin. Notably, administration of 0.2 mg·kg⁻¹ simvastatin 2 h after BDL induction also decreased cholestatic liver injury and inflammation.

Conclusions and implications:

These findings show that simvastatin protects against BDL-induced liver injury. The hepatoprotective effect of simvastatin is mediated, at least in part, by reduced formation of CXC chemokines and leukocyte recruitment. Thus, our novel data suggest that the use of statins may be an effective strategy to protect against the hepatic injury associated with obstructive jaundice.     

Tricyclic antidepressant pharmacology and therapeutic drug interactions updated

New data on the pharmacology of tricyclic antidepressants (TCAs), their affinities for human cloned CNS receptors and their cytochrome P450 enzyme inhibition profiles, allow improved deductions concerning their effects and interactions and indicate which of the TCAs are the most useful. The relative toxicity of TCAs continues to be more precisely defined, as do TCA interactions with selective serotonin reuptake inhibitors (SSRIs). TCA interactions with monoamine oxidase inhibitors (MAOIs) have been, historically, an uncertain and difficult question, but are now well understood, although this is not reflected in the literature. The data indicate that nortriptyline and desipramine have the most pharmacologically desirable characteristics as noradrenaline reuptake inhibitors (NRIs), and as drugs with few interactions that are also safe when coadministered with either MAOIs or SSRIs. Clomipramine is the only available antidepressant drug that has good evidence of clinically relevant serotonin and noradrenaline reuptake inhibition (SNRI). These data assist drug selection for monotherapy and combination therapy and predict reliably how and why pharmacodynamic and pharmacokinetic interactions occur. In comparison, two newer drugs proposed to have SNRI properties, duloxetine and venlafaxine, may have insufficient NRI potency to be effective SNRIs. Combinations such as sertraline and nortriptyline may therefore offer advantages over drugs like venlafaxine that have fixed ratios of SRI/NRI effects that are not ideal. However, no TCA/SSRI combination is sufficiently safe to be universally applicable without expert knowledge. Standard texts (e.g. the British National Formulary) and treatment guidelines would benefit by taking account of these new data and understandings.     

The role of melatonin in the antipsychotic and motor-side effects of neuroleptics: a hypothesis.

Three phenomena concerning the antipsychotic action of classic neuroleptic drugs have not been adequately explained by the dopamine hypothesis: (1) administration of neuroleptic drugs is commonly associated with an initial period of 3-6 weeks prior to demonstration of antipsychotic effects; (2) similarly, neuroleptic-induced Parkinsonism commonly emerges only after several weeks of neuroleptic therapy; (3) moreover, Parkinsonism may disappear despite continuous neuroleptic treatment. An understanding of these phenomena might shed new light into the nature of the antipsychotic actions of these agents, and hence the pathophysiology of schizophrenia. We propose that the increase in melatonin secretion, which occurs with the initiation of neuroleptic therapy, may be responsible for the delay in the antipsychotic effects of neuroleptics and may also account for the lag in the development of drug-induced Parkinsonism as well as its disappearance. The implications of this hypothesis for the treatment of schizophrenia and the prophylaxis of drug-induced Parkinsonism are discussed.     

Spinal metastases mimicking low back pain of mechanical origin: a case report

Spinal malignancies are an essential consideration when a patient presents to a chiropractic office with back pain. This single case report exemplifies the importance of patient presentation and physical examination findings. We must also consider the rationale for x-raying patients on an individual case basis. Textbook cases do not always exist and special diagnostic tests do not always provide a definitive diagnosis of underlying pathology. Even though history and examination findings suggest a routine diagnosis, continual re-evaluation and recognition of the need to change the diagnosis on occasion is extremely important. The patient should not only be thoroughly evaluated upon initial presentation, but also each time they present for treatment. The decision to x-ray a patient is considered important. X-ray examination can be used to confirm a diagnosis or to rule out potential pathologies, and not necessarily done as a routine screening procedure.A case report is presented in which the pathologic signs were not evident on plain film x-rays upon initial presentation.