Benign breast changes and the risk for subsequent breast cancer: an update of the 1985 consensus statement. Cancer Committee of the College of American Pathologists

The Cancer Committee of the College of American Pathologists has prepared an update of the consensus statement on premalignant breast lesions and breast cancer risk that was originally published in the Archives of Pathology & Laboratory Medicine in 1986. The objective of this publication is to better define the relative breast cancer risk associated with specific histologic abnormalities by incorporating data derived from recent case-control studies. Explanatory notes are used to document and explain specific risk classifications. In addition to refining the degree of risk associated with individual lesions, such as fibroadenoma and atypical hyperplasia, this update includes a discussion of age-specific breast cancer risk and provides examples that can be used when counseling patients.     

Comparative study of the pharmacodynamic and pharmacologic effects of Betaseron and AVONEX

The aim of this 1 week study was to compare the biologic effects induced by Betaseron and AVONEX using their approved dose, route, and schedule. Sixteen healthy volunteers were randomly assigned to receive either a single i.m. dose of AVONEX (6 million International Units [MIU]) or, every other day s.c. doses of Betaseron (8 MIU). Common side effects associated with interferon-beta (IFN-beta) treatment and biologic response parameters (neopterin, beta2-microglobulin, interleukin-10 [IL-10], and MxA protein levels in blood) were measured. Ibuprofen was administered to all subjects throughout the study. Fever, chills, and myalgia occurred most frequently and with the greatest severity between 6 and 12 h after the first dose of either IFN-beta. Despite the additional dosing of subjects in the Betaseron group, the incidence, duration, and severity of the side effects were not significantly different from those in the AVONEX group. Biologic response parameters reached similar maximum concentrations in both treatment groups. In the Betaseron group, neopterin and beta2-microglobulin levels remained significantly greater than baseline throughout the 7 day study, whereas those in the AVONEX group were elevated only through day 5. Betaseron treatment significantly increased IL-10 levels above baseline, but AVONEX treatment did not. The overall induction of neopterin, beta2-microglobulin, and IL-10 (as measured by area under the concentration-time curve) was significantly greater in the Betaseron group than the AVONEX group (p = 0.031). The results of this study demonstrate that the approved Betaseron dosing regimen, in combination with ibuprofen use, provided a significantly greater and more consistently elevated biologic response compared with that of AVONEX and did so with a side effects profile comparable to that of once a week AVONEX dosing.     

The edge-to-edge technique: a simplified method to correct mitral insufficiency

OBJECTIVE: Repair of mitral regurgitation (MR) is more demanding in case of prolapse of the anterior leaflet, posterior leaflet with calcified annulus, or prolapse of both leaflets. We evaluated a repair which consists of anchoring the free edge of the prolapsing leaflet to the corresponding free edge of the facing leaflet: the 'edge-to-edge' (E-to-E) technique. The correction results in a double orifice valve when the prolapse is in the middle portion of the leaflet and in a smaller valve orifice when the prolapse is close to a commissure. METHODS: Out of 432 patients with MR submitted to valve repair between January 1991 and September 1997, 121 (mean age 56 +/- 15.8 years) underwent E-to-E correction. The most prevalent etiology was degenerative disease (82 patients, 68%). The mechanism of MR was anterior leaflet prolapse (61 patients), posterior leaflet prolapse (24 patients), prolapse of both leaflets (28 patients) and other complex mechanisms (8 patients). In 72 patients, a double orifice was created, the paracommissural repair was done in 49 patients. RESULTS: Hospital mortality was 1.6%. Overall survival was 92 +/- 3.1% at 6 years with 95 +/- 4.8% freedom from reoperation. Mortality was unrelated to the type of repair. Mitral stenosis was never observed after the correction. At the follow-up (mean 2.2 +/- 1.5 years), all patients but 15 are class I or II. Symptoms at the follow-up are not related to residual MR. CONCLUSIONS: Midterm results of this alternative repair technique are promising, considering the high prevalence of complex anatomical lesions. The technique is simple, easily reproducible and rapidly feasible also when mitral exposure is suboptimal.     

Importance of intramembrane carboxylic acids for occlusion of K+ ions at equilibrium in renal Na,K-ATPase

Site-directed mutagenesis and assay of Rb+ and Tl+ occlusion in recombinant Na,K-ATPase from yeast were combined to establish structure-function relationships of amino acid side chains involved in high-affinity occlusion of K+ in the E2[2K] form. The wild-type yeast enzyme was capable of occluding 2 Rb+ or Tl+ ions/ouabain binding site or alpha 1 beta 1 unit with high apparent affinity (Kd(Tl+) = 7 +/- 2 microM), like the purified Na,K-ATPase from pig kidney. Mutations of Glu327(Gln,Asp), Asp804(Asn, Glu), Asp808(Asn, Glu) and Glu779(Asp) abolished high-affinity occlusion of Rb+ or Tl+ ions. The substitution of Glu779 for Gln reduced the occlusion capacity to 1 Tl+ ion/alpha 1 beta 1-unit with a 3-fold decrease of the apparent affinity for the ion (Kd(Tl+) = 24 +/- 8 microM). These effects on occlusion were closely correlated to effects of the mutations on K0.5(K+) for K+ displacement of ATP binding. Each of the four carboxylate residues Glu327, Glu779, and Asp804 or Asp808 in transmembrane segments 4, 5, and 6 is therefore essential for high-affinity occlusion of K+ in the E2[2K] form. These residues either may engage directly in cation coordination or they may be important for formation or stability of the occlusion cavity.     

Alteration without change?: a commentary on the proposed policy reforms of the British National Health Service

Magnesium chloride (MgCl2) has been proposed for the treatment of seizures of different etiologies. The present study investigated the effect of MgCl2 on aldrin-induced seizures. Initially, 50 male rats received 60 mg aldrin/kg po and the effects were classified as muscular twitches, clonic convulsions or tonic-clonic convulsions. Another group of 40 rats dosed with 60 mg aldrin/kg po received 0, 4, 8, or 12 mg MgCl2/kg i.m. The percentage of tonic-clonic convulsant rats that resulted from MgCl2 treatment were 90% at 0 mg/kg, 50% at 4 mg/kg, 40% at 8 mg/kg and 20% at 12 mg MgCl2/kg. The percentage of survivors in the group receiving 12 mg MgCl2/kg was 80% while the control group had 20% survival. The clonic convulsions were not modified by MgCl2 treatment. Blood and brain concentrations of aldrin and dieldrin (metabolite of aldrin) did not differ among groups. The MgCl2 administration decreased the neuroexcitability induced by aldrin and increased survivability.     

Purification and characterization of maize starch synthase I and its truncated forms

A number of imidazole-based compounds were tested for their utility as (1)H NMR molecular probes of intracellular pH. Imidazole, previously found useful as a probe of erythrocyte pH, reported a pH in perfused canine glioma cells that was more than 1 pH unit lower than that reported by inorganic phosphate, consistent with the known lysosomal compartmentation of the molecule. Imidazole acetate, also proposed as an NMR probe of cellular pH, was found not to enter the cells of this study. Histidine was found to be readily taken up by cells and reported a pH consistent with that reported by inorganic phosphate. Using the chemical shift of the histidine H2 proton in cells incubated with 10 mM histidine, cellular pH measurements could be obtained in less than 1 s. This compares quite favorably with the measurement time, typically several minutes, needed to assess in vivo pH by (31)P NMR. The use of histidine as a probe of pH is demonstrated in perfused canine and rat glioma cells subjected to ischemia or to low extracellular pH.     

Basic Oxygen Furnace: Assessment of Recent Physicochemical Models

Metallurgical and Materials Transactions B - Modeling of the basic oxygen furnace (BOF) process, both for online monitoring and fundamental research, has gained importance in steelmaking industry...     

Design, synthesis, and characterization of a photoactivatable flavocytochrome molecular maquette

We report the construction of a synthetic flavo-heme protein that incorporates two major physiological activities of flavoproteins: light activation of flavin analogous to DNA photolyase and rapid intramolecular electron transfer between the flavin and heme cofactors as in several oxidoreductases. The functional tetra-alpha-helix protein comprises two 62-aa helix-loop-helix subunits. Each subunit contains a single cysteine to which flavin (7-acetyl-10-methylisoalloxazine) is covalently attached and two histidines appropriately positioned for bis-his coordination of heme cofactors. Both flavins and hemes are situated within the hydrophobic core of the protein. Intramolecular electron transfer from flavosemiquinone generated by photoreduction from a sacrificial electron donor in solution was examined between protoporphyrin IX and 1-methyl-2-oxomesoheme XIII. Laser pulse-activated electron transfer from flavin to meso heme occurs on a 100-ns time scale, with a favorable free energy of approximately -100 meV. Electron transfer from flavin to the lower potential protoporphyrin IX, with an unfavorable free energy, can be induced after a lag phase under continuous light illumination. Thus, the supporting peptide matrix provides an excellent framework for the positioning of closely juxtaposed redox groups capable of facilitating intramolecular electron transfer and begins to clarify in a simplified and malleable system the natural engineering of flavoproteins.     

The effect of Pseudomonas aeruginosa infection on clinical parameters in steady-state bronchiectasis

STUDY OBJECTIVE: To investigate the effect of Pseudomonas aeruginosa infection on clinical parameters in Chinese patients with noncystic fibrosis and steady-state bronchiectasis. DESIGN: Prospective, cross-sectional clinicomicrobiological study with informed consent. SETTING: Consecutive outpatient recruitment from a specialist bronchiectasis respiratory clinic. PATIENTS: Outpatients (n = 100; 62 women; 55.1+/-16.7 years old; FEV1/FVC 1.4+/-0.7/2.1+/-0.9 L), who had stable respiratory symptoms for more than 3 weeks. MEASUREMENTS AND RESULTS: Respiratory pathogens isolated from the sputum were: Pseudomonas aeruginosa (33), Haemophilus influenzae (10), Moraxella catarrhalis (2), other Gram-negative bacilli (5), Streptococcus pneumoniae (6), Staphylococcus aureus (5), mycobacteria (3), and yeast (1). Clinical parameters in patients with positive isolation of P aeruginosa were compared with those without the organism in the sputum culture (non-P aeruginosa). In the P aeruginosa group, the FEV1/FVC ratio and sputum volume were lower (p < 0.005) and higher (p < 0.0001), respectively, than those of the non-P aeruginosa group. The FEV1/FVC ratio (< 60%) and sputum volume (grading > 5) were independently associated with a positive sputum isolation of P aeruginosa with odds ratios of 3.1 (confidence interval [CI] 1.2 to 8.4; p < 0.01) and 4.7 (CI 1.6 to 13.3; p < 0.001), respectively. CONCLUSIONS: P aeruginosa is the predominant respiratory pathogen isolated in the sputum of Chinese patients with steady-state bronchiectasis, and its isolation is associated with high sputum output (> or = 75th quartile) and moderately severe airflow obstruction (FEV1/FVC < 60%).