Chemotherapy of lepromatous leprosy: Recent developments and prospects for the future

Leprosy is a major debilitating infectious disease, primarily of the developing world. In this paper the current status and future prospects of antimicrobial therapy of the severe anergic lepromatous form of the disease are reviewed. Until the last few years only dapsone, rifampicin, clofazimine and ethionamide have had practical application in its therapy, and only rifampicin was bactericidal. Recently, antibiotics from three different classes have been found to be bactericidal in lepromatous patients: a tetracycline (minocycline), a macrolide (clarithromycin), and several fluoroquinolones (including pefloxacin, ofloxacin and sparfloxacin). Against a background of drug resistance and bacterial persistence, recommendations for multidrug therapy and the means to devise rationally based therapy for the future are discussed.     

Lactobacillus sakei: recent developments and future prospects

Lactobacillus sakei is one of the most important bacterial species involved in meat preservation and meat fermentation. In the last fifteen years, numerous studies have focused on this species due to its important role in food microbiology. The present paper reviews current knowledge of this emerging species in the fields of taxonomy, phylogeny and physiology, and metabolism. Recent developments in genetic tools and molecular genetics will also be emphasized to evaluate future prospects.     

Current status and future prospects for biologic treatments of psoriasis

Introduction: Biological agents have transformed psoriasis treatment by selectively targeting immune signaling molecules involved in psoriasis pathogenesis. While biologics offer the most effective treatment of moderate to severe psoriasis, they are not without complications. Some patients treated with biologics have poor clinical responses, form anti-drug antibodies, or develop adverse events. Additionally, there is growing need for head-to-head studies comparing biologic treatment regimens, efficacy, and safety.

Areas covered: Here we review the literature surrounding biologics already in clinical use and those undergoing development and clinical trials. We also investigate the development and approval of small molecules inhibitors and biosimilars used to treat psoriasis.

Expert commentary: As the psoriasis treatment armamentarium continues to expand, it is important to follow the safety profile of these drugs both in clinical trials and in post-marketing registries to ensure their long-term safety. Physicians must be aware of the limitations of existing safety data of a drug and the potential risk for rare adverse events when selecting appropriate treatments and monitoring patient outcomes.     

Current status and future prospects for a vaccine against schistosomiasis

Schistosomiasis remains an intractable problem in many parts of the world. Whereas the schistosome parasites cause little in the way of disease, their eggs become trapped in tissues of the host and elicit powerful and potentially damaging immune responses that are responsible for the pathology. Despite nearly four decades of effort there is still no effective vaccine against schistosomiasis, although a single vaccine candidate is undergoing clinical trials at present. Animal models have revealed much about disease progression and pathology. However, problems remain in identifying appropriate protective antigens to elicit immune responses that will attack the parasite but will not cross-react with egg antigens and thus increase the chance of developing severe chronic disease in individuals that have already been infected. This review summarizes the life-cycle of the parasite, current knowledge of pathogenesis and acquired immunity based on animal studies and observations in humans and the status of efforts in the vaccine development field.     

Bioengineering aspects of heart valve replacement

Biomedical engineering inputs have been important in the design, development and testing of substitute heart valves as well as in the pre- and post-operative management of patients with cardiac valve disease. This paper is a review of heart valve replacement whose goal is the enhancement of future bioengineering contributions. We review the approach to the patient with valvular heart disease, and the sources of early and late postoperative pathology with emphasis on complications of the prostheses used. Major significant problem areas relate to the noninvasive evaluation of cardiovascular function (both before and after surgery), device design, hemodynamics, and the need for thromboresistant and durable materials.     

Current and future therapy for hereditary angioedema

Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. Attacks of angioedema in HAE patients typically last 3 or more days, begin during childhood, and continue to occur throughout life. Tragically, patients with HAE continue to die as a direct consequence of the disease. Minimizing the morbidity and mortality associated with HAE requires both effective treatment of acute attacks as well as strategies to prevent HAE attacks. While there is currently no effective therapy available in the United States for the treatment of acute attacks of HAE, several molecules have demonstrated impressive efficacy in this setting, and it is likely that one or more of these new drugs will become available in the United States soon. This article will review both the current and the future therapeutic options for the treatment of HAE.     

Evaluation of antibiotic therapy following valve replacement for native valve endocarditis

We retrospectively evaluated 105 patients at the Mayo Clinic between 1970 and 2006 with native valve endocarditis who underwent acute valve surgery. The objective was to determine if outcomes differed based on whether they had received an antibiotic regimen recommended for native valve endocarditis or one for prosthetic valve endocarditis. Fifty-two patients had streptococcal and 53 had staphylococcal infections. Patients with each type of infection were divided into two groups: the first received postoperative monotherapy (with a beta-lactam or vancomycin), and the second received combination therapy (with an aminoglycoside for streptococcal infection, and gentamicin and/or rifampin for staphylococcal infection). The duration and types of antibiotics given pre- and postoperatively, valve cultures results, antibiotic-related adverse events, relapses, and mortality rates within 6 months of surgery were analyzed. Cure rates were similar regardless of the regimen administered. With the small number of patients in each group, a multicenter study with a larger cohort of patients is needed to better define optimal postoperative treatment regimens in this population.     

Current status and future prospects for the treatment of antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a prothrombotic disease characterized by thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (apL). Management of thrombosis is based on long-term oral anticoagulation and patients with arterial events should be treated aggressively. Primary thrombo-prophylaxis is recommended in patients with systemic lupus erythromatosus (SLE) and obstetric APS. Obstetric APS care is based on high-risk management and treatment with aspirin and heparin. Possible future therapies include statins, hydroxychloroquine, rituximab, and new anticoagulant drugs. Current research is focused on targeting components of the complement system, interfering with aPL–mediated cell activation and using tailored peptides to block the pathogenic subpopulation of aPL.     

迷走神经电刺激治疗癫痫的现状与展望

Electrical vagus nerve stimulation （VNS） has been approved by FDA and is widely used in recent years for the treatment of epilepsy and possibly other medical conditions such as depression. The current success rate of VNS for epilepsy is about 50%, but there are complications, potential risks and cost concerns. One of the major limitations for this new therapy is that its antiseizure mechanisms are by no means clear. In particular, it is not known whether the therapeutic effect is vagal specific, what types of nerve fibers in the vagus nerve are contributing to the therapeutic effects, or what individual patients would benefit from the use of the expensive and invasive VNS implantation. There are controversies regarding how and where the VNS takes effect on epilepsy in the central nervous system. The poor understanding of VNS has inevitably limited the application and success of the therapy. The current review analyses the pros and cons of VNS for epilepsy in vis-à- vis other available therapies including Chinese medical methods, and explores the possible mechanisms in order to stimulate further improvement of this new technology.     

Current status and future prospects for a vaccine against American trypanosomiasis

The clinically relevant pathognomonic consequences of human infection by Trypanosoma cruzi are dilation and hypertrophy of the left ventricle walls and thinning of the apex. The major complications and debilitating evolutionary outcomes of chronic infection include ventricular fibrillation, thromboembolism and congestive heart failure. American trypanosomiasis (Chagas disease) poses serious public healthcare and budgetary concerns. The currently available drugs, although effective against acute infection, are highly toxic and ineffective in arresting or attenuating clinical disease symptoms in chronic patients. The development of an efficacious prophylactic vaccine faces many challenges, and progress is slow, despite several years of effort. Studies in animal models and human patients have revealed the pathogenic mechanisms during disease progression, pathology of disease and features of protective immunity. Accordingly, several antigens, antigen-delivery vehicles and adjuvants have been tested in animal models, and some efforts have been successful in controlling infection and disease. This review will summarize the accumulated knowledge about the parasite and disease, as well as pathogenesis and protective immunity. The authors will discuss the efforts to date, and the challenges faced in achieving an efficient prophylactic vaccine against human American trypanosomiasis, and present the future perspectives.     

Phage therapy: past history and future prospects

Bacterial viruses (bacteriophages, also called "phages") can be robust antibacterial agents in vitro. However, their use as therapeutic agents, during a number of trials from the 1920s to the 1950s, was greatly handicapped by a number of factors. In part, there were certain limitations inherent in phage physiology (e. g. narrow host range, and rapid clearance from the body); in part there were technological limitations in the era (e.g. lysogeny not yet discovered); but the greatest limitation was the highly inadequate scientific methodologies used by practitioners at the time (e.g., their failure to conduct placebo-controlled studies, to remove endotoxins from the preparations, and to re-confirm phage viability after adding sterilizing agents to the preparations). In recent years, well-controlled animal models have demonstrated that phages can rescue animals from a variety of fatal infections, while non-controlled clinical reports published in Eastern Europe have shown that phages can be effective in treating drug-resistant infections in humans. This encouraging data, combined with the fact that drug-resistant bacteria have become a global crisis, have created a window of opportunity for phage therapy to be tested anew, this time using modem technologies and placebo-controlled designs. If successful, it can be used as a stand-alone therapy when bacteria are fully resistant to antibiotics, and as a valuable adjunct to antibiotics when the bacteria are still susceptible.     

Current status and future prospects of decellularized kidney tissue

Journal of Artificial Organs - End-stage renal disease (ESRD) is characterized by progressive loss of kidney function, which can result in damage to various tissues and organs. Dialysis therapy and...     

Use of prothrombin fragment 1+2 for evaluating anticoagulant therapy after mechanical heart valve replacement

Prothrombin fragment 1+2 (F1+2) is a coagulation factor newly used as a molecular marker to monitor anticoagulant therapy in patients undergoing heart valve replacement. We evaluated the usefulness of F1+2 against that of prothrombin time (PT) reported as the internationalized normalized ratio (INR) in 93 patients undergoing mechanical heart valve implantation between August 1999 and July 2000. The study group consisted of 38 men and 55 women, with an average age of 61.1±11.2 years. The surgeries were 34 aortic replacements, 9 double valve replacements, and 50 mitral valve replacements. Warfarin doses were controlled based on PT-INR values at a target range of 1.5–2.5 F1+2 levels in the 0.4–1.2 nmol/l level were considered normal. No thromboembolism or bleeding complication occurred in any patient during the mean follow-up period of 12 months. The overall correction coefficient between F1+2 and PT-INR was 0.165 (P<0.001). A few specimens showed abnormally high levels of F1+2, even when PT-INR values were within the optimal range. The plasma levels of F1+2 that fell within normal range came from specimens with PT-INR values <1.50. The plasma levels of F1+2 that corresponded to PT-INR values of 1.50–2.50 fell just within the normal range, and the F1+2 levels corresponding to PT-INR values >2.50 were less than half of the lower limit of normal. Our analysis involving F1+2 confirmed PT-INR in the 1.5–2.5 range following mechanical heart valve implantation to be optimal. We found that using F1+2 to monitor individual response to anticoagulation therapy is useful when PT-INR values are difficult to obtain.     

Gene therapy for muscular dystrophies: current status and future prospects

Since the identification in 1987 of the gene for Duchenne muscular dystrophy (DMD), research on the molecular pathogenesis of muscular dystrophy has progressed extensively. In particular, discovery of the DMD gene product, dystrophin, led to the identification of dystrophin-associated proteins and, subsequently, the recognition of other types of muscular dystrophy caused by the defects in each of the sarcoglycan genes. On the other hand, effective therapy for DMD has not yet been established. Some of the viral vectors, such as adenoassociated virus vectors or lentiviral vector, have been proven to enable the longterm expression of the exogenous gene without overt host immune reactions. However, dystrophin cDNAs are too large (14kb) to be accommodated in these viral vectors. To solve this problem, we and other research groups succeeded in truncating full-length dystrophin cDNA to small dystrophin cDNA (4 to 5kb), the products of which protect dystrophin-deficient mdx muscle from contractioninduced membrane damage when introduced by viral vectors or as a transgene into mdx mice. The usefulness of these truncated dystrophin cDNAs should be confirmed using other animal models such as dystrophic dogs. To develop successful treatment of DMD, the authors believe that several different approaches should be used, such as cell transfer therapy, drug design to up-regulate utrophin, or a strategy to repair the mutation in vivo.     

Return to work after heart valve replacement

One hundred patients who underwent heart valve replacement during the years 1977 to 1985 were reviewed an average of 57 months after surgery. The overall rate of reemployment after the operation was 78%. The most important factors influencing the return to work were the employment status before surgery, age at the time of surgery, the number and site of the diseased valve, the preoperative New York Heart Association (NYHA) functional class and the number of times cardiac surgery was performed. These factors were closely related to the optimal timing of heart valve replacement. It was suggested that the rate of return to work and the quality of life would be improved if the heart valve replacement had been performed at an earlier stage of the disease.     

Targeted therapy for upper gastrointestinal tract cancer: current and future prospects

Gastric and oesophageal carcinoma remain major causes of worldwide mortality and morbidity. Despite incredible progress in understanding tumour biology, few targeted treatment options have proved effective in prolonging survival, and adjuvant therapy is largely interchangeable in these carcinomas. Through large‐scale sequencing by the Cancer Genome Atlas and the Asian Cancer Research Group, numerous potential molecular targets have been discovered. Of the approved targeted therapies for gastric and oesophageal cancer, pathologists play a role in patient selection for the majority of them. Trastuzumab has been approved as a first‐line therapy in conjunction with standard treatment in adenocarcinomas with either 3+ HER2/neu expression by immunohistochemistry or ERBB2 amplification by FISH. PD‐L1 immunohistochemistry showing a combined positive score of 1 or greater qualifies patients for third‐line pembrolizumab therapy, and identification of microsatellite instability‐high carcinomas may qualify patients for second‐line pembrolizumab. Ramucirumab, targeting VEGFR2, has also been approved for second‐line therapy in gastric carcinoma. Non‐surgical therapy for gastrointestinal stromal tumours relies mainly upon tyrosine kinase inhibitors, while new targeted therapy options for neuroendocrine neoplasms have recently emerged. Potential future options for targeted therapy in all these malignancies are being investigated in clinical trials, as this review will discuss.