HLA-G expression in cancers: potential role in diagnosis, prognosis and therapy

Human leukocyte antigen G (HLA-G) is a non-classic major histocompatibility complex (MHC) class I molecule that functions as an immune suppressive molecule. HLA-G has direct inhibitory effects on natural killer cells(NK), dendritic cells (DC), T cells and has long-term tolerogenic indirect effects by inducing regulator T cells (Treg). HLA-G has been reported to be involved in various physio-pathological conditions such as reproduction, transplantation, autoimmunity, infectious and malignant diseases. In this context, aberrant expression of HLA-G in malignant diseases including hematological and solid tumors has been extensively investigated and its relevance to clinicoparameters and potential significance in diagnosis, prognosis and immune target therapy has been postulated. We here summarized the HLA-G expression in malignancies and emphasis its clinical relevance to malignant disease diagnosis, prognosis, and its potential in target-based immunotherapy was also discussed.     

Pharmacotherapy for hypertension in pregnant patients: special considerations

Introduction: Hypertensive disorders of pregnancy (HDP) represent a major cause of maternal, fetal and neonatal morbidity and mortality and identifies women at risk for cardiovascular and other chronic diseases later in life. When antihypertensive drugs are used during pregnancy, their benefit and harm to both mother and fetus should be evaluated.

Areas covered: This review summarizes the pharmacological characteristics of the recommended antihypertensive drugs and their impact on mother and fetus when administered during pregnancy and/or post-partum. Drugs were identified using MEDLINE and the main international Guidelines for the management of HDP.

Expert opinion: Although there is a consensus that severe hypertension should be treated, treatment of mild hypertension without end-organ damage (140–159/90–109 mmHg) remains controversial and there is no agreement on when to initiate therapy, blood pressure targets or recommended drugs in the absence of robust evidence for the superiority of one drug over others. Furthermore, the long-term outcomes of in-utero antihypertensive exposure remain uncertain. Therefore, evidence-based data regarding the treatment of HDP is lacking and well designed randomized clinical trials are needed to resolve all these controversial issues related to the management of HDP.     

Drug therapy in transplant recipients: special considerations in the elderly with comorbid conditions

Elderly patients with end-stage organ failure are now more frequently undergoing transplantation. Medication management in this population is challenging because of the combination of multiple comorbidities, polypharmacy, and immunological, pharmacokinetic and pharmacodynamic changes attributable to the aging process. Immunosuppressive medications can exacerbate pre-existing medical conditions and promote the development of disease processes.Cardiovascular disorders, such as hypertension, coronary artery disease, congestive heart failure and arrhythmias are common in elderly transplant recipients, and account for most of the deaths in this population. Blood pressure, blood glucose and cholesterol control is of particular concern because elderly transplant recipients frequently have or develop these complications. Elderly transplant recipients are commonly receiving anticoagulation therapy with warfarin and are at a higher risk of bleeding, especially if they have renal dysfunction.Infectious complications occur frequently in the transplanted population, with pneumonia being the most common infection seen in hospitalised patients. Attention to vaccination for the prevention of influenza and pneumococcal infections is important because of the increased risk of these diseases in this population. Depression itself has been associated with decreased survival in older individuals, and depression in elderly transplant recipients may be reversible with the administration of pharmacological agents.Effective long-term care of transplant recipients demands an understanding of how particular medications affect clinical evaluation and treatment. This article addresses some of the practical issues surrounding medication management and prevention of these particular problems in elderly transplant recipients.     

Hormonal contraception in adolescents: special considerations

With the rates of unintended pregnancies in teenagers remaining high, it is crucial to present adolescents with all of the contraceptive options available to them. While barrier methods, for example, male condoms, are easily accessible and do not have adverse effects, their use must be consistent and correct with each act of intercourse. Hormonal contraception affords much better efficacy in preventing pregnancy when used with full compliance.Oral contraceptives are a popular method of contraception among adolescents and offer many non-contraceptive benefits along with the prevention of pregnancy. They have very few significant adverse effects, which are outweighed by the significant morbidity associated with teenage pregnancies, and can be used by most adolescent females. However, their minor bothersome effects do contribute to the high discontinuation rates seen. In addition, many girls find it difficult to remember to take a pill every day, leading to higher failure rates in teenagers than in adult women. The advent of long-acting, progestogen (progestin)-only methods, such as injectables and implantables, has been generally accepted by adolescents and these methods have proven to be more efficacious by avoiding the need for daily compliance. However, progestogen-only methods cause irregular bleeding and amenorrhea, which is not acceptable to many teenagers. In addition, the most widely used implant was taken off the market a few years ago and newer forms are not yet widely accessible.Other novel methods are currently available, including the transdermal patch and the vaginal ring. Both are combinations of estrogen and progestogen and have similar efficacy and adverse effect profiles to oral contraceptives. Their use may be associated with greater compliance by adolescents because they also do not require adherence to a daily regimen. However, there may be some drawbacks with these newer methods, for example, visibility of the patch and difficulty with insertion of the vaginal ring.When regular contraceptive modalities fail, emergency contraception is available. Choices include combination oral contraceptives, progestogen-only pills, mifepristone, or placement of a copper-releasing intrauterine device. These methods can be very useful for preventing pregnancy in adolescents as long as adolescents are aware of their existence and have easy access to them.     

Drug dosing during intermittent hemodialysis and continuous renal replacement therapy : special considerations in pediatric patients

Chronic renal failure is, fortunately, an unusual occurrence in children; however, many children with various underlying illnesses develop acute renal failure, and transiently require renal replacement therapy - peritoneal dialysis, intermittent hemodialysis (IHD), or continuous renal replacement therapy (CRRT). As children with acute and chronic renal failure often have multiple comorbid conditions requiring drug therapy, generalists, intensivists, nephrologists, and pharmacists need to be aware of the issues surrounding the management of drug therapy in pediatric patients undergoing renal replacement therapy. This article summarizes the pharmacokinetics and dosing of many drugs commonly prescribed for pediatric patients, and focuses on the management of drug therapy in pediatric patients undergoing IHD and CRRT in the intensive care unit setting. Peritoneal dialysis is not considered in this review. Finally, a summary table with recommended initial dosages for drugs commonly encountered in pediatric patients requiring IHD or CRRT is presented.     

Liraglutide: clinical pharmacology and considerations for therapy

Liraglutide is a United States Food and Drug Administration (FDA)-approved glucagon-like peptide-1 (GLP-1) analog that is 97% homologous to native human GLP-1. The additional 16-carbon fatty acid chain causes noncovalent binding to albumin, which slows absorption from the injection site and protects the molecule from degradation by the enzyme dipeptidyl peptidase-4, allowing for protraction of action. Albumin binding and an elimination half-life of 13 hours combine to allow for once-daily dosing. Liraglutide 1.2 and 1.8 mg/day given as monotherapy for up to 52 weeks produced mean reductions in hemoglobin A1c (A1C) of 0.6-1.6%; combination therapy of liraglutide with oral antidiabetic agents demonstrated mean A1C reductions up to 1.5%. The satiety effect of GLP-1 receptor agonists and documented weight loss as great as 3.38 kg in clinical trials may make liraglutide ideal for obese patients with type 2 diabetes mellitus. Like other incretin-based agents, preliminary studies suggest liraglutide may also increase β-cell mass and function. Hypoglycemia is rare with liraglutide and tends to occur when used in combination with sulfonylureas; liraglutide in combination with insulin is not yet FDA approved. The pharmacokinetic parameters of liraglutide are unaffected by age, sex, race, or ethnicity, and no special recommendations for altered dosing of liraglutide need apply to populations with hepatic or renal impairment. Results from clinical trials have not shown an increased risk of medullary thyroid cancer, pancreatitis, or poor cardiovascular outcomes with liraglutide treatment. Ongoing, long-term monitoring studies continue to evaluate the safety of liraglutide treatment in these outcomes.     

A new alternative therapy in dermatology: tocilizumab

Tocilizumab (TCZ) is a recombinant-humanized anti-human interleukin 6 receptor monoclonal antibody of the immunoglobulin (Ig) IgG1 subclass with a H2L2 polypeptide structure. Even if it was approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis and polyarticular juvenile idiopathic arthritis, satisfying results have also been reported with TCZ in various refractory dermatological diseases such as psoriasis, psoriatic arthritis, Behçet's disease, systemic lupus erythematosus, systemic sclerosis, relapsing polychondritis, vasculitis and atopic dermatitis. TCZ treatment in dermatology and adverse effects of the drug were reviewed here after the pharmacological properties, mechanism of action, dosage and administration of the drug were summarized. We estimate that by the help of newly well-designed studies with wider spectrum of subjects to comprehensively investigate the efficacy and safety will be able to contribute to the clinical management of the diseases especially refractory to the other treatments. Therefore, during the next decade, TCZ will be promising drugs in the treatment of refractory dermatological diseases.     

Heparin-induced thrombocytopenia: treatment options and special considerations

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse effect that typically manifests several days after the start of heparin therapy, although both rapid- and delayed-onset HIT have been described. Its most serious complication is thrombosis. Although not all patients develop thrombosis, it can be life threatening. The risk of developing HIT is related to many factors, including the type of heparin product administered, route of administration, duration of therapy, patient population, and previous exposure to heparin. The diagnosis of HIT is typically based on clinical presentation, exposure to heparin, and presence of thrombocytopenia with or without thrombosis. Antigen and activation laboratory assays are available to support the diagnosis of HIT. However, because of the limited sensitivity and specificity of these assays, bedside probability scales for HIT were developed. When HIT is suspected, prompt cessation of all heparin therapy is necessary, along with initiation of alternative anticoagulant therapy. Two direct thrombin inhibitors--argatroban and lepirudin--are approved for the management of HIT in the United States, and bivalirudin is approved for use in patients with HIT who are undergoing percutaneous coronary intervention. Other agents, although not approved to manage HIT, have also been used; however, their role in therapy requires further evaluation. A comprehensive HIT management strategy involves the evaluation of numerous factors. Many patients, including those undergoing coronary artery bypass surgery, those with acute coronary syndromes, those with hepatic or renal insufficiency, and children, require special attention. Clinicians must become familiar with the available information on this serious adverse effect and its treatment so that optimum patient management strategies may be formulated.     

Topical fenticonazole in dermatology and gynaecology: current role in therapy

Fenticonazole is an imidazole derivative with a broad spectrum of antimycotic activity against dermatophytes and yeasts in in vitro and clinical studies. Fenticonazole exerts its unique antimycotic mechanism of action in the following three ways: (i) inhibition of the secretion of protease acid by Candida albicans; (ii) damage to the cytoplasmic membrane; and (iii) by blocking cytochrome oxidases and peroxidises. Fenticonazole has also been shown to exhibit antibacterial action, with a spectrum of activity that includes bacteria commonly associated with superinfected fungal skin and vaginal infections, and antiparasitic action against the protozoan Trichomonas vaginalis. Therefore, fenticonazole may be an ideal topical alternative to multi-agent treatment of mixed infections involving mycotic, bacterial, dermatophyte and/or Trichomonas spp.Open-label clinical studies show that fenticonazole, in different pharmaceutical preparations administered once or twice daily, is effective in the treatment of superficial mycoses of the skin. In particular, fenticonazole is very effective (often with 100% of patients achieving a negative mycological assay) in pityriasis versicolor and candidiasis. For example, a large (n = 760) study showed fenticonazole 2% cream, spray or powder to be associated with a mycological response in 100% of patients with pityriasis versicolor, 96.3% of those with tinea infections and 95.2% of patients with Candida infections. Comparative clinical studies show fenticonazole once or twice daily to be at least as effective as six different topical antimycotics (miconazole, clotrimazole, econazole, bifonazole, naftifine and cyclopyroxolamine) in the treatment of superficial mycoses of the skin. Intravaginal administration of fenticonazole is associated with a high rate of microbiological efficacy in patients with vaginal candidiasis, trichomoniasis, mixed infection and bacterial vaginosis. Intravaginal fenticonazole is at least as effective as clotrimazole and shows similar efficacy to miconazole in patients with vaginal candidiasis. Fenticonazole has a rapid onset of action and clinical efficacy is generally observed within days of commencing treatment.Topical fenticonazole is very well tolerated; adverse events are generally mild to moderate in severity and transient. The most frequent adverse events are burning sensation/cutaneous irritation and itch when applied to the skin. In a large, open-label study in superficial mycoses of the skin, the incidence of adverse events was <5% and these were rarely responsible for treatment discontinuation. Burning sensation is the most common adverse event seen with fenticonazole when administered intravaginally. However, this symptom of vaginal fungal infection was often present in patients prior to drug administration.Given the rising incidence of superficial fungal, and possibly mixed, infections, topical fenticonazole represents an important part of the topical antimycotic armamentarium.     

Oncologic complications of human immunodeficiency virus infection: changing epidemiology, treatments, and special considerations in the era of highly active antiretroviral therapy

Although highly active antiretroviral therapy (HAART) has revolutionized the treatment of human immunodeficiency virus (HIV)-positive patients, malignancies in the setting of HIV infection remain an appreciable problem. We evaluated the changing epidemiology of HIV-related malignancies, optimal neoplastics and their effect on viral dynamics, and evidence regarding drug interactions between chemotherapy and antiretrovirals. A MEDLINE search (January 1966-June 2006) was performed to identify clinical trials, review articles, and meta-analyses; abstracts from HIV conferences were also searched. Survival of patients with HIV-related malignancies has substantially improved since the advent of HAART. Chemotherapy for malignancies in the HIV-positive population generally resembles that for the HIV-negative population, with trials revealing an elevated frequency of toxicities in HIV-positive patients. Studies of antineoplastics have shown no long-term adverse effects on viral dynamics in terms of immunologic or virologic HIV markers. Limited pharmacokinetic data with antineoplastics and antiretrovirals suggest possible changes in some pharmacokinetic parameters, but these results should be interpreted cautiously because of the small numbers of patients enrolled in the trials. Researchers also report an increased frequency of chemotherapy-related toxicities when HAART was coadministered with antineoplastics. This increase was likely due to impairment of cytochrome P450 metabolism of antineoplastics by protease inhibitors. Because of the survival benefits of HAART, the integration of antiretrovirals with chemotherapy is now preferred for patients with HIV-related malignancies. However, because the metabolic pathways of many of these agents are similar, the effectiveness of antineoplastic therapy and its related toxicities should be vigilantly monitored in this patient population.     

Lung cancer--epidemiology, prognosis and therapy

Lung cancer is one of the most common cancer diagnoses, sadly with a bad prognosis. The main risk factor is smoking. There are two major types of lung cancer: non-small cell lung cancer und small cell lung cancer. The difference is important for prognosis and therapy. The prognosis for patients with small-cell lung cancer is worse; the treatment is based on chemotherapy. In patients with non-small cell lung cancer surgery and radiotherapy are more important.     

Management of uveitis in pediatric patients: special considerations

Uveitis refers to inflammation involving the uvea or middle coat of the eye. This condition occurs uncommonly, particularly in persons aged 相似文献   

Glucosamine therapy for knee osteoarthritis: pharmacokinetic considerations

Knee osteoarthritis is the most common form of arthritis. Given the aging of the world’s population, the burden of this disease is expected to increase significantly over the next few decades. As a pharmacological agent, glucosamine has been investigated for the treatment of symptoms and progression of knee osteoarthritis, demonstrating symptomatic and disease-modifying effects. However, among the glucosamine studies conducted to date in knee osteoarthritis, there have been conflicting results due to differences and/or weaknesses in study design and sample size, in addition to product formulation, salt and quality. This review describes the current knowledge regarding the pharmacokinetics of glucosamine to provide a means for the interpretation of the pharmacodynamic and clinical efficacy results obtained in the different clinical trials.     

Glucosamine therapy for knee osteoarthritis: pharmacokinetic considerations

Knee osteoarthritis is the most common form of arthritis. Given the aging of the world's population, the burden of this disease is expected to increase significantly over the next few decades. As a pharmacological agent, glucosamine has been investigated for the treatment of symptoms and progression of knee osteoarthritis, demonstrating symptomatic and disease-modifying effects. However, among the glucosamine studies conducted to date in knee osteoarthritis, there have been conflicting results due to differences and/or weaknesses in study design and sample size, in addition to product formulation, salt and quality. This review describes the current knowledge regarding the pharmacokinetics of glucosamine to provide a means for the interpretation of the pharmacodynamic and clinical efficacy results obtained in the different clinical trials.     

Biochemical markers of neurotoxicity in wildlife and human populations: considerations for method development

Disruption of neurochemical parameters in blood and brain tissues can be used as early biomarkers of neurotoxicity in human and wildlife epidemiological studies. To investigate the feasibility of biomarker measurements in field samples obtained from remote locations, tissue storage limits were determined with human blood and mink cortex tissue using efficient and cost-effective microplate assays. Results show that isolated blood platelets and plasma can be stored at 4 degrees C for 4 wk before measurement of monoamine oxidase (MAO) and cholinesterase (ChE) activities, while human lymphocytes can be stored at 4 degrees C for up to 2 d before muscarinic acetylcholine (mACh) receptor binding analysis. Blood cells stored frozen resulted in decreased MAO activity and mACh receptor function. These data suggest that mink brain tissue obtained from field samples can be stored at various temperatures without affecting dopamine (D2) and mACh receptor densities; however, MAO and ChE activities were most stable in samples stored in a -20 degrees C domestic freezer or at 4 degrees C. Multiple freeze/thaw cycles alter mACh and D2 receptors and MAO activity in mink cortex samples and should therefore be minimized. In conclusion, these neurochemical biomarkers can efficiently be measured in large human and wildlife neurotoxicity studies, provided proper storage conditions are maintained.     

Antiretroviral therapy 2006: Pharmacology, applications, and special situations

As we approach the completion of the first 25 years of the human immunodeficiency virus (HIV) epidemic, there have been dramatic improvements in the care of patients with HIV infection. These have prolonged life and decreased morbidity. There are twenty currently available antiretrovirals approved in the United States for the treatment of this infection. The medications, including their pharmacokinetic properties, side effects, and dosing are reviewed. In addition, the current approach to the use of these medicines is discussed. We have included a section addressing common comorbid conditions including hepatitis B and C along with tuberculosis.