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Limited Treatment Options (limited + treatment_option)

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Medical Sciences	100%

Selected Abstracts

Cutaneous infections in the elderly: diagnosis and management

DERMATOLOGIC THERAPY, Issue 3 2003
Jeffrey M. Weinberg
ABSTRACT:, Over the past several years there have been many advances in the diagnosis and treatment of cutaneous infectious diseases. This review focuses on the three major topics of interest in the geriatric population: herpes zoster and postherpetic neuralgia (PHN), onychomycosis, and recent advances in antibacterial therapy. Herpes zoster in adults is caused by reactivation of the varicella-zoster virus (VZV) that causes chickenpox in children. For many years acyclovir was the gold standard of antiviral therapy for the treatment of patients with herpes zoster. Famciclovir and valacyclovir, newer antivirals for herpes zoster, offer less frequent dosing. PHN refers to pain lasting ,2 months after an acute attack of herpes zoster. The pain may be constant or intermittent and may occur spontaneously or be caused by seemingly innocuous stimuli such as a light touch. Treatment of established PHN through pharmacologic and nonpharmacologic therapy will be discussed. In addition, therapeutic strategies to prevent PHN will be reviewed. These include the use of oral corticosteroids, nerve blocks, and treatment with standard antiviral therapy. Onychomycosis, or tinea unguium, is caused by dermatophytes in the majority of cases, but can also be caused by Candida and nondermatophyte molds. Onychomycosis is found more frequently in the elderly and in more males than females. There are four types of onychomycosis: distal subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis, and candidal onychomycosis. Over the past several years, new treatments for this disorder have emerged which offer shorter courses of therapy and greater efficacy than previous therapies. The treatment of bacterial skin and skin structure infections in the elderly is an important issue. There has been an alarming increase in the incidence of gram-positive infections, including resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant pneumococci. While vancomycin has been considered the drug of last defense against gram-positive multidrug-resistant bacteria, the late 1980s saw an increase in vancomycin-resistant bacteria, including vancomycin-resistant enterococci (VRE). More recently, strains of vancomycin-intermediate resistant S. aureus (VISA) have been isolated. Gram-positive bacteria, such as S. aureus and Streptococcus pyogenes are often the cause of skin and skin structure infections, ranging from mild pyodermas to complicated infections including postsurgical wound infections, severe carbunculosis, and erysipelas. With limited treatment options, it has become critical to identify antibiotics with novel mechanisms of activity. Several new drugs have emerged as possible therapeutic alternatives, including linezolid and quinupristin/dalfopristin. [source]

Immunopathogenesis of hepatitis C virus infection and hepatic fibrosis: New insights into antifibrotic therapy in chronic hepatitis C

HEPATOLOGY RESEARCH, Issue 8 2007
Rosângela Teixeira
Fibrosis and cirrhosis represent the consequences of a sustained wound-healing response to chronic liver injury of any cause. Chronic hepatitis C virus (HCV) has emerged as a leading cause of cirrhosis in the USA and throughout the world. HCV may induce fibrogenesis directly by hepatic stellate cell activation or indirectly by promoting oxidative stress and apoptosis of infected cells. The ultimate result of chronic HCV injury is the accumulation of extracellular matrix with high density type I collagen within the subendothelial space of Disse, culminating in cirrhosis with hepatocellular dysfunction. The treatment of hepatitis C with the combination of pegylated interferon and ribavirin is still both problematic and costly, has suboptimal efficacy, serious side effects and a high level of intolerance, and is contraindicated in many patients. Hence, new approaches have assumed greater importance, for which there is an urgent need. The sustained progress in understanding the pathophysiology of hepatic fibrosis in the past two decades has increased the possibility of developing drugs specifically targeting the fibrogenic process. Future efforts should identify genetic markers associated with fibrosis risk in order to tailor the treatment of HCV infection based on genetically regulated pathways of injury and/or fibrosis. Such advances will expand the arsenal to overcome liver fibrosis, particularly in patients with hepatic diseases who have limited treatment options, such as those patients with chronic hepatitis C who have a high risk of fibrosis progression and recurrent HCV disease after liver transplantation. [source]

A United States compassionate use study of lamivudine treatment in nontransplantation candidates with decompensated hepatitis B virus,related cirrhosis

LIVER TRANSPLANTATION, Issue 1 2003
Hie-Won L. Hann MD
Patients with hepatitis B,related decompensated cirrhosis have limited treatment options. This prospective, multicenter study assessed lamivudine in 75 patients with decompensated cirrhosis, the majority of whom (93%) were not candidates for liver transplantation. At baseline, all 75 patients tested positive for hepatitis B surface antigen [HBsAg (+)] and 62% tested positive for hepatitis B e antigen [HBeAg (+)]. Hepatitis B virus (HBV) DNA levels were detectable in 64% of patients by the branched chain DNA (bDNA) assay. Patients received lamivudine 100 mg once daily (median duration, 12.7 months; range, 0.5 to 33 months). In patients with detectable HBV DNA pretreatment, the virus became undetectable by the bDNA assay in 69% of patients with , 6 months treatment and in 64% overall. Alanine aminotransferase (ALT) level improved in 90% and normalized in 55% of patients with , 6 months treatment and in 48% overall. Improvements in bilirubin and albumin levels occurred throughout treatment. The median Child-Pugh score improved from a baseline of 10 to 8 at last visit, with 31% (23/75) having an improved score of , 2 points, 57% (43/75) unchanged (< 2 points), and 12% (9/75) worsened (, 2 points). A virologic breakthrough developed in eight of 41 patients (18%) after a median of 13.1 months of treatment. Tyrosine-methionine-aspartate-aspartate (YMDD) variant HBV was detected in three of four patients tested. Nevertheless, at last visit, ALT, albumin, and bilirubin levels were similar for patients with and without breakthrough. Lamivudine treatment can lead to significant improvements in liver disease severity in nontransplantation candidates with advanced disease. Additional studies of lamivudine in combination with other antivirals are indicated for the large population of patients worldwide with advanced HBV-related cirrhosis and inadequate access to liver transplantation. [source]

Development of chondrosarcoma animal models for assessment of adjuvant therapy

ANZ JOURNAL OF SURGERY, Issue 5 2009
J. C. M. Clark
Abstract Chondrosarcoma is a primary cancer of bone causing significant morbidity due to local recurrence and limited treatment options. Relatively few chondrosarcoma animal models have been developed, and the only orthotopic model is technically demanding and has limited clinical relevance. The aim of this review is to assess the features of current animal chondrosarcoma models for the purpose of developing new models in which to test adjuvant chondrosarcoma therapy. The available literature on this topic was identified using the PubMed database, and then analysed for relevance to the human chondrosarcoma disease and feasibility in testing new therapeutic agents. Animal-derived chondrosarcoma models comprise predominantly allograft tumour transplanted into the rat (Swarm rat chondrosarcoma) or the hamster. These types of models are less relevant to the human disease and have been more useful for evaluation of chondrosarcoma growth and histology than in developing novel therapeutic agents. The athymic nude mouse has enabled reliable human xenograft transplantation. A number of human chondrosarcoma cell lines have been successfully used to generate tumours in this species, including OUMS-27 and HCS-2/A. Although effective in demonstrating anti-tumour effects of a number of agents, the lack of a representative orthotopic model diminishes overall clinical relevance. More clinically relevant models of human chondrosarcoma progression are required either through transgenic mice or orthotopic human xenograft models. [source]