Malignancy-associated changes in lactiferous duct epithelium.

Objective: To determine whether cells from histologically normal appearing epithelium of the lactiferous duct from women with a remote ductal lesion in the breast provide any clues indicating the existence of such a lesion.

Study Design: Tissue sections cut to 4 microns and stained with hematoxylin and eosin were prepared from duct tissue of 20 women with breast lesions and of 20 women free of any such lesion who had undergone mammoplastic procedures or resection for benign reasons. One hundred nuclei were measured from each case.

Refractory vasomotor angina in subclinical hyperthyroidism demonstrating focal and segmental coronary vasoconstriction.

We describe a case of refractory vasomotor angina in the setting of unrecognized subclinical hyperthyroidism. Despite aggressive medical therapy, frequent rest angina recurred until diagnosis and treatment of Grave s Disease, which presented asymptomatically. Both spontaneous focal vasospasm and inducible segmental coronary vasoconstriction were demonstrated during invasive provocative testing.

Role of therapy or monitoring in preventing progression to gastric cancer.

It is generally accepted that intestinal-type gastric adenocarcinoma arises through a multistep process originating with chronic gastritis, progressing through stages of atrophy, intestinal metaplasia, and dysplasia and finally invasive carcinoma. This sequential process, known as the "Correa cascade" is in many instances initiated by Helicobacter pylori infection and perpetuated by a number of environmental and host factors. Given that the development of carcinoma can be the end point of this sequential process, there is great interest in determining which if any of these steps may be reversible.

Hypermethylation of the gene promoter and enhancer region can regulate Fas expression and sensitivity in colon carcinoma.

Expression of the cell surface receptor Fas is frequently lost or decreased during tumor progression in human colon carcinomas. The methylation status of a 583 bp CpG-rich region within the Fas promoter (-575 to +8) containing 28 CpG sites was determined in human colon carcinoma cell lines. In Caco(2) (no Fas expression), 82-93% of CpG sites were methylated, whereas none were methylated in GC(3)/c1 (high Fas expression).

Metastatic breast lobular carcinoma involving tamoxifen-associated endometrial polyps: report of two cases and review of tamoxifen-associated polypoid uterine lesions.

Two cases of lobular breast carcinoma metastatic to an endometrial polyp are described. Both patients had been treated with tamoxifen and presented with abnormal uterine bleeding. Histology of endometrial biopsy in both cases showed typical tamoxifen-associated endometrial polyps with focal subtle stromal infiltration by metastatic lobular breast carcinoma.

Cystic fibrosis mutation frequencies in an Irish population.

The incidence of cystic fibrosis (CF) at birth in Ireland is 1/1461. Neonate CF genetic testing is not routinely performed in Ireland. Currently, screening is only carried out where there is clinical evidence or a family history to suggest disease.

Transfection of IL-10 expression vectors into endothelial cultures attenuates alpha4beta7-dependent lymphocyte adhesion mediated by MAdCAM-1.

Background: Enhanced expression of MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is associated with the onset and progression of inflammatory bowel disease. The clinical significance of elevated MAdCAM-1 expression is supported by studies showing that immunoneutralization of MAdCAM-1, or its ligands reduce inflammation and mucosal damage in models of colitis. Interleukin-10 (IL-10) is an endogenous anti-inflammatory and immunomodulatory cytokine that has been shown to prevent inflammation and injury in several animal studies, however clinical IL-10 treatment remains insufficient because of difficulties in the route of IL-10 administration and its biological half-life.

Off-line particle size analysis of digested sludge.

Particle size analysis was carried out on six samples of digested sludge using laser diffraction. The digested sludge was produced in laboratory-scale reactors under different feed regimes based on a mixture of primary and waste activated sludge (WAS). Laser diffraction proved capable of providing rapid, reproducible results of the particle size distribution of each sample, and highlighted differences between the different treatments.

Nutrient intake and nutritional indexes in adults with metastatic cancer on a phase I clinical trial of dietary methionine restriction.

Animal studies have shown that dietary methionine restriction selectively inhibits growth of a variety of human tumor xenografts but has relatively few deleterious effects on normal tissues. The objectives of the present study were to determine whether enteral methionine restriction is safe and tolerable in adults with metastatic cancer and whether it reduces plasma methionine levels. Eight patients with a variety of metastatic solid tumors were enrolled in a phase I clinical trial.

Effect of influent organic content on digested sludge extracellular polymer content and dewaterability.

The organic composition of the feed sludge to six laboratory-scale anaerobic digesters was adjusted by substituting a proportion of the primary sludge for glucose or propionic acid solution. Substitution with glucose caused an increase in the microbial extracellular polymer (ECP) content of the digested sludge, which altered the particle size distribution of the sludge and made the sludge more difficult to dewater. Substitution with propionic acid gave similar results to the control.

Modulation of the Fas signaling pathway by IFN-gamma in therapy of colon cancer: phase I trial and correlative studies of IFN-gamma, 5-fluorouracil, and leucovorin.

Potentiation of 5-fluorouracil/leucovorin (FUra/LV) cytotoxicity by IFN-gamma in colon carcinoma cells is dependent on FUra-induced DNA damage, the Fas death receptor, and independent of p53 and RNA-mediated FUra toxicity, which occurs in normal gastrointestinal tissues. This provides a rationale for enhancing the selective action of FUra/LV by IFN-gamma in the treatment of colorectal carcinoma. Based on results from our preclinical studies we designed a Phase I trial combining FUra (370 mg/m2) and LV (200 mg/m2), i.

Upper airway obstruction and acute lung injury associated with cocaine abuse.

We describe the case of a 14-year-old boy who developed airway obstruction due to acute upper respiratory tract infection. Following emergency tracheostomy, he developed pulmonary oedema and required ventilation. The postoperative course was complicated by the development of adult respiratory distress syndrome, characterised by marked respiratory distress, diffuse pulmonary infiltrates on chest radiography, reduced pulmonary compliance and marked increase in alveolar-arterial oxygen difference.

Inducible nitric oxide synthase knockout mice are resistant to diet-induced loss of gut barrier function and intestinal injury.

Loss of gut barrier function has been documented to occur in animals receiving total parenteral nutrition (TPN) and certain liquid diets. However, the mechanisms responsible for diet-induced gut barrier dysfunction remain to be fully determined. Thus we tested the hypothesis that increased intestinal nitric oxide production contributes to this phenomenon.

Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial.

Background: In the adjuvant setting, tamoxifen is the established treatment for postmenopausal women with hormone-sensitive breast cancer. However, it is associated with several side-effects including endometrial cancer and thromboembolic disorders. We aimed to compare the safety and efficacy outcomes of tamoxifen with those of anastrozole alone and the combination of anastrozole plus tamoxifen for 5 years.

Gastric cancer: laboratory bench to clinic.

Gastric cancer is the second most common cause of cancer-related mortality worldwide and the 14th overall cause of death. Detection of disease usually occurs at an advanced stage and overall survival rates for gastric cancer are poor. Our current model for gastric cancer progression clearly maintains Helicobacter infection as the primary inducer of gastric metaplastic and neoplastic disease.

The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine.

Objectives: The purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine.

Background: Endothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide.

Trends in the incidence of childhood diabetes in south Asians and other children in Bradford, UK.

Aims: To investigate incidence rates and time trends, over 21 years, of Type 1 diabetes in a migrant population of south Asian children in Bradford, UK.

Methods: Children (0-14 years) living in the city of Bradford and diagnosed with Type 1 diabetes were selected from a population-based region-wide register. Between 1978 and 1998, 289 new-onset cases were registered and classified as south Asian (Indian, Pakistani, Bangladeshi) or not, based on their full name using two different computer algorithms and visual inspection.

A preliminary report on the implication of RT-PCR detection of DAZ, RBMY1, USP9Y and Protamine-2 mRNA in testicular biopsy samples from azoospermic men.

In this study, reverse transcription-polymerase chain reaction (RT-PCR) was optimized to analyse the presence of DAZ, RBMY1, USP9Y, protamine-2, SRY and actin messenger RNA (mRNA) in testicular cells of men suffering from idiopathic azoospermia. All samples (n=28), including five controls, showed normal expression of actin, SRY and USP9Y. Sperm was not recovered from eight patients after testicular biopsy.

Termination of lifespan of SV40-transformed human fibroblasts in crisis is due to apoptosis.

Normal human fibroblasts in culture have a limited lifespan, ending in replicative senescence. Introduction of SV40 sequences encoding large T antigen and small t antigen into pre-senescent cells results in an extension of lifespan for an additional 20-30 population doublings. Rare clones of SV40-transformed cells are capable of indefinite growth and are described as immortal; however, the great majority of SV40-transformed cells terminate this extended lifespan in cell death, termed "crisis.

Human plasma is directly bacteriocidal against Helicobacter pylori in vitro, potentially explaining the decreased detection of Helicobacter pylori during acute upper GI bleeding.

Background: The rapid urease test is the preferred method for detection of H pylori in patients with uncomplicated ulcer disease undergoing EGD. However, the sensitivity of this test when performed during upper GI bleeding has been questioned. It has been suggested that false-negative results occur, resulting from buffering effects of blood.

Prominent dyserythropoiesis in four cases of haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis (HLH) is a disease characterised by peripheral blood pancytopenia secondary to haemophagocytosis of formed blood cells by activated histiocytes. The demonstration of haemophagocytosis may be difficult and the diagnosis may require repeated tissue sampling (including bone marrow, cerebrospinal fluid, lymph nodes, spleen, and liver) and the demonstration of associated clinical or laboratory features. This report describes pronounced dyserythropoiesis in the bone marrow aspirates in four patients with HLH, including familial and secondary cases.