Advances in molecular carcinogenesis: current and future use of mouse models to screen and validate molecularly targeted anticancer drugs

Survival of patients with advanced solid tumors has not significantly improved over the past 30 years. Although molecularly targeted anticancer drugs offer promise, few drugs make it through the end of the Food and Drug Administration approval process. Animal models that more closely resemble human carcinogenesis may bridge the gap between preclinical success and benefits for patients. We discuss pros and cons of several mouse models, including genetically engineered mice that each represent different aspects of human cancer, and the screening of targeted drugs in these models.     

The epidemiology of fatty liver

There are insufficient data available on the epidemiology of fatty liver to design a complete and correct view of the prevalence, incidence and natural history of this disorder. This article, mainly based on the revision of recently published papers in this field, attempts to give an overview of the current findings on the epidemiology of fatty liver worldwide. The possible factors involved in the development of fat accumulation in the liver, and their potential role in the progression of the disorder will be also addressed.     

Cytomegalovirus pneumonitis in a patient with Hodgkin disease and ataxia-telangiectasia

We describe a child with with Hodgkin disease and ataxia-telangiectasia who also developed an unusual pneumonitis caused by a cytomegalovirus which was fatal.     

Psychometric evaluation of the Children's Yale-Brown Obsessive-Compulsive Scale

This study evaluated the psychometric properties of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). A total of 61 children and adolescents, aged 4-18 years, who were diagnosed with obsessive-compulsive disorder (OCD) participated. Thirty-seven of these children also participated in a second CY-BOCS administration by the same rater an average of 41 days later. Good internal consistency and test-retest reliability were found for the CY-BOCS Obsession and Compulsion Severity Scores and the Total Score. CY-BOCS scores demonstrated strong correlations with clinician-rated measures of impairment, obsessions, and compulsions. In addition, CY-BOCS scores were moderately related to measures of depression, aggressive behavior, and symptoms of attention deficit hyperactivity disorder, but were not significantly related to clinician ratings of tics or self-reports of general anxiety. Findings suggest that the CY-BOCS is a reliable and valid instrument for the assessment of childhood obsessions and compulsions.     

Management of atherothrombosis with clopidogrel in high-risk patients with recent transient ischaemic attack or ischaemic stroke (MATCH): study design and baseline data

BACKGROUND: The CAPRIE study showed the superiority of clopidogrel over acetylsalicylic acid (ASA) for reducing the combined risk of major atherothrombotic events in patients with recent myocardial infarction (MI), recent ischaemic stroke (IS) or established peripheral arterial disease. The benefit of clopidogrel over ASA is amplified in high-risk patients. Proof of concept for the benefit of clopidogrel in addition to ASA in patients with coronary manifestations of atherothrombosis was provided by the CURE trial. METHODS: MATCH is a randomized, double-blind, placebo-controlled trial that compares clopidogrel and ASA versus clopidogrel alone in high-risk patients with recently symptomatic cerebrovascular disease. Eligible patients have experienced a transient ischaemic attack (TIA) or IS within the last 3 months and have evidence of at least 1 additional risk factor within the last 3 years (prior IS, MI, stable or unstable angina pectoris, diabetes or symptomatic peripheral arterial disease). Patients were randomized to receive ASA 75 mg once daily or placebo, with both groups receiving clopidogrel 75 mg once daily as part of standard therapy. The primary end point is the composite of IS, MI, vascular death and rehospitalization for an acute ischaemic event. The duration of treatment and follow-up is 18 months for each patient. RESULTS: Enrollment was completed in April 2002, with 7,599 patients randomized to receive the study medication. The mean age at randomization was 66 years, and the qualifying event was IS in 78.9% of patients and TIA in 21.1%. The baseline features of the study cohort indicate a population that is at a high risk for atherothrombotic recurrence. CONCLUSION: MATCH is a major ongoing trial that will provide important data on the benefit of clopidogrel and ASA compared with clopidogrel alone for reduction of vascular ischaemic events in patients with recent TIA or IS who are at high risk of atherothrombotic event recurrence.