脂肪性肝病的治疗对策

当前酒精性肝病(ALD)患病率居高不下，而非酒精性脂肪性肝病(NAFLD)发病率不断攀高，且起病渐趋低龄化，两者与病毒性肝炎并存者亦不少见。更为可怕的是，NAFLD不但与ALD相似，可导致肝硬化、肝细胞癌和肝功能衰竭，而且与2型糖尿病以及动脉硬化性心脑血管事件关系密切。然而迄今尚缺乏防治脂肪性肝病(FLD)的特效药物，现有对策主要为“提高认识、综合防治，加强宣教，重在实施”。     

Lung diseases during therapeutic aplasia: diagnostic and therapeutic strategy

Lung diseases that occur in patients with drug-induced bone marrow aplasia are part of a wider group of lung diseases in immunocompromised patients. Their most common causes are infections due to Gram-negative bacilli, staphylococci or Aspergillus spp. and intra-alveolar haemorrhages. Their diagnostic approach is often limited by disorders of coagulation, risks of infection by bronchial or pulmonary seeding during endoscopy and the lethal risk of mechanical ventilation after bronchoalveolar lavage in patients with respiratory failure. The therapeutic approach is frequently empirical due to the fact that antibiotic therapy cannot be delayed, even for a few hours, and to the aforementioned diagnostic problems. In practice, the diagnostic and therapeutic approaches usually result from a rational compromise depending on whether the lung disease has occurred at the onset or at the end of an episode of bone marrow aplasia.     

关于"血液病/恶性肿瘤患者侵袭性真菌感染的诊断标准与治疗原则(修订版)"

近年来侵袭性真菌感染的发病率明显上升,且病情危重复杂,而侵袭性真菌感染的临床诊断手段滞后,许多患者尚未明确诊断就因病情危重死亡。3～5年前国内可应用于临床有效且安全的抗真菌药物种类不多,故侵袭性真菌感染成了临床治疗上的难题。3年多来,随着有效的抗真菌药物纷纷出现,通过多层次的交流、研讨,不仅大大提高了临床的治疗水平,挽救了众多患者的生命,     

Blocking lymphocyte localization to the gastrointestinal mucosa as a therapeutic strategy for inflammatory bowel diseases

Lymphocyte migration (homing) to specific tissues has an important role during protective and pathological immune responses, including inflammatory bowel diseases. Lymphocytes use integrin α4β7 and the chemokine receptor CCR9 to localize to the gastrointestinal mucosa; their respective ligands, mucosal addressin cell adhesion molecule-1 and CCL25, are displayed on endothelial cells in intestinal postcapillary venules. Although gastrointestinal-homing receptors are required for lymphocyte migration to the intestine in the noninflamed steady state, their role during inflammation is a matter of debate. Reagents designed to block interactions between these receptors and their ligands have had variable degrees of success in animal models of inflammatory bowel diseases and patients. We discuss the mechanisms involved in lymphocyte localization to the intestinal mucosa and how they can be applied to therapy for inflammatory bowel diseases.     

Novel therapeutic options for osteoporosis

Osteoporosis remains a significant clinical problem despite effective therapies. Many patients cannot or will not take currently available therapies. For this reason, research continues in search of more effective and more tolerable agents. Arzoxifene and TSE-424 are investigational selective estrogen receptor modulators that have been shown to be effective in animal studies and are now in clinical studies. Tibolone is a tissue-specific steroid that is currently used in Europe for the prevention and treatment of osteoporosis. Multiple studies have shown efficacy in improving bone mineral density, but no fracture studies have been conducted to date. Although studies of the effect of isoflavones on bone mineral density have been encouraging, a large multicenter study in Europe recently showed no effect of isoflavones on fractures. The investigational bisphosphonates ibandronate and zoledronic acid may offer the advantage of less frequent dosing. The newly described agent osteoprotegerin has been shown in early studies to inhibit bone turnover. Finally, the issue of efficacy of statins in bone continues to be debated with no prospective, randomized studies yet to confirm the suggestion of benefit seen in epidemiologic studies.     

Novel therapeutic approaches for haemophilia

The major therapy for haemophilia is plasma derived or recombinant clotting factors which are evolving steadily to increase potency, stability and half‐life. Research in the area of haemophilia therapeutics, however, is not restricted only to modifications in the recombinant products, but alternate therapeutic strategies are being developed which are in different phases of experimental and clinical trials. This chapter reviews the diverse molecular innovations which are being developed for alternate therapeutic approaches in haemophilia. The data is mainly extracted from the literature and the Conference abstracts. Some of the novel therapeutic approaches include inhibition of anticoagulant pathway factors (activated protein C, antithrombin, tissue factor pathway inhibitor) by monoclonal antibodies, peptide inhibitors, DNA or RNA aptamers, use of variant coagulation factors (factor Xa, factor Va) which are more resistant to inactivation or enzymatically more active and antibody‐mediated therapy including a humanized anti‐factor IXa/X bispecific antibody mimicking factor VIII. Other approaches include nonsense mutation suppression, induction of prothrombotic microparticles by P‐selectin‐immunoglobulin chimeras, suppression of fibrinolytic potential either by antifibrinolytics or by the use of mutant molecules of fibrinolytic inhibitors. Few products are proposed as ‘stand alone’ treatment for haemophilia, while a few can be used as adjuvant therapies to recombinant factors with an aim to reduce the amount of factor intake. All efforts are underway to produce an alternate, novel drug for haemophilia which will have an increased half‐life, subcutaneously injectable, non‐immunogenic and effective both in the presence and absence of inhibitors.     

Sepsis in patients with hematological diseases

Sepsis is one of the important complications on the treatment of severe hematological diseases. In this report, we analyzed sepsis in 309 patients with hematological diseases who were admitted to the First Department of Internal Medicine of Yokohama City University Hospital from 1979 to 1986. Positive blood culture were found in 17.8% (55/309 cases) and total positive cases were 73 including recurrent patients. Positive rate by underlying diseases was 30.3% in acute leukemia, 20.8% in chronic myelocytic leukemia, 17.2% in aplastic anemia, 8.0% in multiple myeloma, 6.0% in malignant lymphoma and 6.5% in others. The organisms causing sepsis were as follows; gram negative bacilli 56.4%, gram positive organisms 34.6%, fungus 6.4% and anaerobic bacteria 2.6%. Pseudomonas aeruginosa was found in 19.2%. The mortality rate of patients with sepsis was 34.2% (25/73 cases). The significant prognostic factors in patients with sepsis were the degree of neutropenia, duration of neutropenia (500 less than microliters), the species of organisms, simultaneous complication with shock and the site of other infections.