Trends in the treatment of ductal carcinoma in situ of the breast.

Background: An increase in incidence of ductal carcinoma in situ (DCIS) of the breast has been documented, and concerns regarding overly aggressive treatment have been raised. This study was designed to evaluate the use of surgery and radiation therapy in treating DCIS.

Methods: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results database to assess treatment of patients with DCIS with no evidence of microinvasion who were diagnosed from January 1, 1992, through December 31, 1999.

Improved survival with radial artery versus vein conduits in coronary bypass surgery with left internal thoracic artery to left anterior descending artery grafting.

Background: Given its proven survival benefit, left internal thoracic artery to left anterior descending (LITA-LAD) grafting has become a fundamental part of CABG. This grafting also led to increased use of other arterial conduits, of which the radial artery is most popular. Whether radial grafting improves survival beyond that achieved by LITA-LAD alone is not known.

Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity.

T regulatory cells and IL-10 have been implicated in the mechanism of immunotherapy in patients with systemic anaphylaxis following bee stings. We studied the role of IL-10 in the induction of clinical, cellular, and humoral tolerance during immunotherapy for local mucosal allergy in subjects with seasonal pollinosis. Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen (Phleum pratense, Phl P) immunotherapy.

Changes in circulating insulin-like growth factor-I, insulin-like growth factor binding proteins, and leptin in weaned pigs infected with Salmonella enterica serovar Typhimurium.

One of the hallmarks of the pathophysiology of enteric disease in young pigs is reduced growth performance. This reduction in growth is associated with changes in the endocrine somatotropic growth axis. Our laboratory previously demonstrated that circulating insulin-like growth factor-I (IGF-I) was reduced in pigs infected with Salmonella enterica serovar Typhimurium (S.

CXCR1+CD4+ T cells in human allergic disease.

Chemokine receptors play an important role in the migration of leukocytes to sites of allergic inflammation in humans. In this study, we have identified increased expression of the chemokine receptor CXCR1 on CD4+ T lymphocytes derived from patients with atopic disease compared with normal donors. Enhanced expression of CXCR1 by atopic donors was identified on freshly isolated peripheral blood cells and on expanded cell populations derived from nasal mucosal biopsies and from the periphery.

Predicting the genotoxicity of polycyclic aromatic compounds from molecular structure with different classifiers.

Classification models were developed to provide accurate prediction of genotoxicity of 277 polycyclic aromatic compounds (PACs) directly from their molecular structures. Numerical descriptors encoding the topological, geometric, electronic, and polar surface area properties of the compounds were calculated to represent the structural information. Each compound's genotoxicity was represented with IMAX (maximal SOS induction factor) values measured by the SOS Chromotest in the presence and absence of S9 rat liver homogenate.

Further experience with gastric stimulation to treat drug refractory gastroparesis.

Background: Gastric electrical stimulation (GES) has been introduced for patients with gastroparesis refractory to pharmacological therapy.

Methods: From April 1998 until November 2001, 55 patients underwent GES implantation at Kansas University Medical Center. All patients had prolonged gastric retention of a solid meal by scintigraphy at baseline.

The CX3C chemokine fractalkine in allergic asthma and rhinitis.

Background: Unlike other chemokines, fractalkine is expressed as a membrane-bound form, mainly on endothelial and epithelial cells, and can be shed as a soluble chemotactic form. Fractalkine can capture leukocytes expressing its receptor (CX(3)CR(1)), including T lymphocytes, rapidly and firmly in an integrin-independent manner. Because of its dual activity, fractalkine plays a major role in the transendothelial and transepithelial migration of leukocytes during inflammation.

Role of tumor necrosis factor receptor 1 (p55) in hepatocyte proliferation during acetaminophen-induced toxicity in mice.

Hepatocyte proliferation represents an important part of tissue repair. In these studies, TNF receptor 1 (TNFR1) knockout mice were used to analyze the role of TNF-alpha in hepatocyte proliferation during acetaminophen-induced hepatotoxicity. Treatment of wild-type (WT) mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis.

Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy.

Background: Among atopic individuals, levels of allergen-specific IgG antibodies have been inversely associated with the degree of allergen sensitization. Additionally, allergen-specific IgG antibodies are markedly increased by allergen injection immunotherapy. These observations have led to proposals that allergen-specific IgG antibodies might have protective properties in atopic individuals.

Local somatic hypermutation and class switch recombination in the nasal mucosa of allergic rhinitis patients.

Immunoglobulin E is produced by nasal B cells in response to allergen. We have analyzed IgE V(H) region sequences expressed in the nasal mucosa of patients suffering from allergic rhinitis. V(H) region sequences were amplified by RT-PCR from IgE(+) B cells from nasal biopsies.

Oxymetazoline nasal spray three times daily for four weeks in normal subjects is not associated with rebound congestion or tachyphylaxis.

Topical decongestants are available over the counter and provide rapid relief of nasal obstruction for conditions of short duration, for example the common cold. Manufacturers' recommendations are that topical decongestants should not be used regularly for more than 1 week in view of the risk of rebound mucosal hyperaemia with persistent nasal obstruction and refractoriness to further effects of decongestants. For this reason we performed a randomised double-blind placebo-controlled trial in 30 normal adult subjects with 0.

Immunomodulatory treatment strategies for allergic diseases.

Over the last decades the prevalence of allergic disorders, such as hayfever and asthma has increased worldwide, mostly in westernised countries where up to 20 % of the population are affected. The "hygiene hypothesis" suggests that modernised lifestyles such as improved housing conditions, altered dietary habits and smaller family sizes may be responsible for the decrease in infectious and the increase in allergic diseases. Childhood atopic diseases, like eczema, food allergies and recurrent wheezy bronchitis represent a considerable health problem and a major socioeconomic burden due to the chronicity of these disorders.

Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor receptor-1. Potential role of inflammatory mediators.

Transgenic mice with a targeted disruption of the tumor necrosis factor receptor 1 (TNFR1) gene were used to analyze the role of TNF-alpha in pro- and anti-inflammatory mediator production and liver injury induced by acetaminophen. Treatment of wild-type mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis. This was correlated with expression of inducible nitric oxide synthase (NOS II) and nitrotyrosine staining of the liver.

Systematic assessment of difficult-to-treat asthma.

Five per cent of asthmatics remain symptomatic despite high-dose treatment. The aim of the study was to investigate how often such difficult-to-treat asthma is due to intractable asthma, misdiagnosis, non-adherence with therapy, or psychiatric problems. Difficult asthma was defined as persistence of symptoms despite treatment at step 4 of British guidelines or requirement for long-term oral glucocorticoids (step 5).

The c-myc x E2F-1/p21 interactive gene expression index augments cytomorphologic diagnosis of lung cancer in fine-needle aspirate specimens.

Morphological analysis of cytologic samples obtained by fine-needle aspirate (FNA) or bronchoscopy is an important method for diagnosing bronchogenic carcinoma. However, this approach has only about 65 to 80% diagnostic sensitivity. Based on previous studies, the c-myc x E2F-1/p21WAF1/CIP1 (p21 hereafter) gene expression index is highly sensitive and specific for distinguishing normal from malignant bronchial epithelial tissues.

Role of p55 tumor necrosis factor receptor 1 in acetaminophen-induced antioxidant defense.

Tumor necrosis factor (TNF)-alpha is a macrophage-derived proinflammatory cytokine implicated in hepatotoxicity. In the present studies, p55 TNF receptor 1 (TNFR1) -/- mice were used to assess the role of TNF-alpha in acetaminophen-induced antioxidant defense. Treatment of wild-type (WT) mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis and increased serum alanine transaminases.

Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed?

Background: Hemodilutional anemia during cardiopulmonary bypass can lead to inadequate oxygen delivery and, consequently, to ischemic organ injury. In adult bypass, the nadir hematocrit can vary widely with body size and prebypass hematocrit variations, yet its effects on perioperative organ dysfunction and patient outcomes remain largely unknown.

Methods: To elucidate these effects, we retrospectively analyzed operative results and resource utilization data from 5000 consecutive cardiac operations with cardiopulmonary bypass performed on adults (1994 to 2000).

Predicting the genotoxicity of thiophene derivatives from molecular structure.

We report several binary classification models that directly link the genetic toxicity of a series of 140 thiophene derivatives with information derived from the compounds' molecular structure. Genetic toxicity was measured using an SOS Chromotest. IMAX (maximal SOS induction factor) values were recorded for each of the 140 compounds both in the presence and in the absence of S9 rat liver homogenate.

Sublingual immunotherapy for allergic rhinitis.

Background: Allergic rhinitis is a common condition which, at its most severe, can significantly impair quality of life despite optimal treatment with antihistamines and topical nasal corticosteroids. Allergen injection immunotherapy significantly reduces symptoms and medication requirements in allergic rhinitis but its use is limited by the possibility of severe systemic reactions. There has therefore been considerable interest in alternative routes for delivery of allergen immunotherapy, particularly the sublingual route.

Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy.

Background: Immunotherapy involves the modulation of allergen-specific T-cell responses, either T(H)2-to-T(H)1 immune deviation or, in bee venom-treated patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing CD4+CD25+ regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology.

Objective: The aim of this study was to evaluate the role of IL-10 production and CD4+CD25+ T cells in the response to grass pollen immunotherapy.