Impact of BMI on serum estradiol and bone turnover markers in postmenopausal women with hormone-sensitive early breast cancer treated with anastrozole.

PURPOSE: Obesity increases the risk of all-cause and breast cancer mortality. As obese patients have higher levels of aromatase enzyme activity, conflicting results on the effect of body mass index (BMI) of a standard dose aromatase inhibitor on estradiol depletion have been reported. METHODS: We prospectively investigated the effect of BMI on the efficacy of anastrozole in 70 postmenopausal women with early, ER-positive breast cancer to decrease serum estradiol assessed by a high-sensitive assay with a sensitivity limit of 5 pg/ml over 24 months. Additionally, we examined the changes of bone markers expecting an inverse relationship. RESULTS: Overall, estradiol decreased from 12.6 pg/ml (SD = 5.4) to 4.0 pg/ml (SD = 5.6) over 24 months (p < 0.001). In contrast, carboxy-terminal collagen crosslinks (CTX) and serum aminoterminal propeptide of type I collagen (PINP) increased from 0.26 ng/ml (SD = 0.18) to 0.40 ng/ml (SD = 0.24) and 41.5 ng/ml (SD = 19.7) to 59.1 ng/ml (SD = 29.1) (p < 0.0001 for both). Baseline estradiol comprised significant differences comparing normal weight with overweight (p < 0.01) or obese patients (p < 0.001). After 12 and 24 months, overweight and obese patients showed a slightly, but insignificantly higher concentrations of estradiol compared to normal weight subjects. We found differences of CTX in comparison between normal weight and obese patients (0.33 vs. 0.21 ng/ml; p < 0.023) at baseline. At 12 and 24 months, there was a significant BMI-independent increase in CTX. CONCLUSIONS: Estradiol concentrations in postmenopausal women with early, ER-positive breast cancer on anastrozole were significantly different in normal weight versus overweight or obese patients at baseline, but not at 12 and 24 months. CTX and PINP present a notable increase in the first 12 months of anastrozole treatment, stabilizing thereafter.

Coalescence of magnetic islands in the low-resistivity, Hall-MHD regime.

The coalescence of magnetic islands in the low-resistivity eta, Hall-MHD regime is studied. The interaction between the ion inertial length d(i) and the dynamically evolving current sheet scale length deltaJ is established. Initially, d(i) << deltaJ. If eta is such that deltaJ dynamically thins down to d(i) prior to the well-known sloshing phenomena, then sloshing is avoided. This results in eta independent peak reconnection rates. However, if d(i) is small enough that deltaJ cannot be thinned down to this scale prior to sloshing, then sloshing proceeds as in the resistive MHD model.

Spondyloenchondromatosis with D-2-hydroxyglutaric aciduria: a report of a second patient with this unusual combination.

Spondyloenchondromatosis (SEM) is a rare skeletal dysplasia which presents with multiple enchondromata in the metaphyses of the long bones associated with dysplastic vertebral bodies. It is probably heterogeneous. We have investigated and documented a male infant in South Africa with spondyloenchondromatosis and persistent D-2-hydroxyglutaric aciduria (D2HA). D2HA is a neurometabolic disorder whose enzymatic basis is still undefined. A girl in England with a similar clinical, radiological and biochemical phenotype has previously been reported by Talkhani et al. [(2000). Skel Radiol 7:215-2921]. There is at present a lack of a plausible pathogenetic relationship between the two components of the disorder but a contiguous gene syndrome or a pleiotropic gene could be considered. Whatever the underlying mechanism this case report confirms its nosological entity.

Magnetic reconnection in the two-dimensional Kelvin-Helmholtz instability.

Magnetic reconnection in the two-dimensional Kelvin-Helmholtz instability is studied. The flow is modeled by the reduced MHD equations with constant resistivity and viscosity. For super-Alfvénic flow, localized transient reconnection is observed on the Kelvin-Helmholtz time scale (this is not new). We study this transient reconnection and consider the peak reconnection rate which occurs with the initial vortex formation. Over the range of resistivities considered, it is shown that this peak reconnection rate is not a function of resistivity, and is a function of the initial flow shear. Additionally, it is demonstrated that there is a fundamental difference between the evolution of a problem at S = 200 and S = 10,000.

Aptamers that bind to the antibiotic moenomycin A.

Nuclease-resistant moenomycin-binding aptamers with dissociation constants in the range of 300 to 400 nM have been selected. Competition experiments have demonstrated that these aptamers recognize a disaccharide analogue of moenomycin. The results offer the opportunity of setting up a selective and sensitive assay for identifying moenomycin biosynthetic precursors.

Transient magnetic reconnection and unstable shear layers.

We study three-dimensional magnetic reconnection caused by the Kelvin-Helmholtz (KH) instability and differential rotation in subsonic and sub-Alfvenic flows. The flows, which are modeled by the resistive magnetohydrodynamic equations with constant resistivity, are stable in the direction of the magnetic field but unstable perpendicular to the magnetic field. Localized transient reconnection is observed on the KH time scale, and kinetic energy increases with decreasing resistivity. As in flux-transfer events in the Earth's magnetopause boundary layer, bipolar structures in the normal flux and bidirectional jetting away from reconnection zones are observed.

Plant-Microbe Interactions: Wetting of Ivy (Hedera helix L.) Leaf Surfaces in Relation to Colonization by Epiphytic Microorganisms.

Leaf wettability, cuticular wax composition, and microbial colonization of upper and lower leaf surfaces of ivy (Hedera helix L.) was investigated for young and old leaves sampled in June and September. Contact angles of aqueous buffered solutions measured on young leaf surfaces ranged between 76° and 86° and were not dependent on the pH value of the applied droplets. Contact angles measured on old leaf surfaces were up to 32°, significantly lower than on young leaf surfaces. Furthermore, contact angles were significantly lower using aqueous solutions of pH 9.0 compared to pH 3.0, indicating the influence of ionizable functional groups on leaf surface wetting properties. Observed changes in leaf wetting properties did not correlate with different levels of alkanoic acids in cuticular waxes. However, microscopic examination of the leaf surfaces indicated the influence of epiphytic microorganisms on wetting properties of old leaves, since their surfaces were always colonized by epiphytic microorganisms (filamentous fungi, yeasts, and bacteria), whereas surfaces of young leaves were basically clean. In order to analyze the effect of epiphytic microorganisms on leaf surface wetting, surfaces of young and clean ivy leaves were artificially colonized with Pseudomonas fluorescens. This resulted in a significant increase and a pH dependence of leaf surface wetting in the same way as it was observed on old ivy leaf surfaces. From these results it can be deduced that the native wetting properties of leaf surfaces can be significantly masked by the presence of epiphytic microorganisms. The ecological implications of altered wetting properties for microorganisms using the leaf/atmosphere interface as habitat are discussed.

Results of a multicenter trial of the CapSure (Re/Stor) Continence shield on women with stress urinary incontinence.

OBJECTIVES: To prospectively study the impact of the CapSure (Re/Stor) Continence shield for the treatment of stress urinary incontinence. METHODS: One hundred women with pure stress urinary incontinence were enrolled in a 6-month study. Objective measures of urine loss included pad weight test (PdWt) and provocative stress test (PST). Subjective measures included incontinence diaries documenting the number of incontinence episodes per day (IEPD), quality of life questionnaires, and satisfaction surveys. Objective and subjective measures were performed prior to enrollment, during use of the CapSure shield, and after discontinuation of the device. RESULTS: During the 12-week device utilization period, PdWt measurements demonstrated a 96% reduction in urine loss by week 1 and 97% by week 12. Eighty-two percent of subjects were completely dry by week 12. PST demonstrated 100% reduction in urine loss at each visit, with 91% of subjects completely dry by week 12. IEPD also demonstrated a 91% reduction in incontinence episodes by week 12. Quality of life scores and patient satisfaction surveys demonstrated significant improvement. During the 6-week post device utilization period (PUP), subjects continued to demonstrate a reduction in urine loss compared to pre-enrollment data, despite discontinuation of use. PdWt measurements demonstrated a 73% and 79% reduction in urine loss at weeks 14 and 18, respectively. Measurements of PST and IEPD demonstrated significant reductions in urine loss at weeks 14 and 18. A 1.5% prevalence of positive urine cultures was noted during device use. Bothersome vaginal or urethral irritation occurred in 12% of patients. Adverse events were few and required no therapeutic intervention. CONCLUSIONS: The CapSure shield is a safe and efficacious method of managing stress urinary incontinence in women.

Influence of epiphytic micro-organisms on leaf wettability: wetting of the upper leaf surface of Juglans regia and of model surfaces in relation to colonization by micro-organisms.

Wetting of the upper leaf surface of Juglans regia L. and of model surfaces colonized by epiphytic micro-organisms was investigated by measuring contact angles of aqueous solutions buffered at different pH values. During June to October 1995, contact angles of aqueous solutions on the leaf surface of J. regia decreased by angles ranging from 12° (low pH values) to 25° at high pH values. At the end of this vegetation period, wetting was strongly dependent on pH showing significantly lower contact angles with alkaline solutions (pH 9·0) than with acidic solutions (pH 3·0). Contact angle titration measured angles on the leaf surface as a function of the pH of buffered aqueous solutions, covering a pH range from 3·0 to 11·0. Titration curves revealed inflection points around 7·5, indicating the existence of ionizable carboxylic groups at the interface of the phylloplane. Altered leaf-surface wetting properties observed on the intact leaf surface could be simulated in model experiments by measuring contact angles on artificial surfaces colonized by Pseudomonas fluorescens and by epiphytic micro-organisms isolated from the phylloplane of J. regia. Strong evidence is provided that interfacial carboxylic groups derive from epiphytic micro-organisms present on the phylloplane. Results suggest that the age-dependent increase in, and pH dependence of, wetting as leaves mature are related to the presence of epiphytic micro-organisms on the phylloplane. Ecological consequences of increased leaf-surface wetting, concerning the structure of the leaf surface as a microhabitat for epiphytic micro-organisms, are discussed.

Evaluation of surgical scrub methods for large animal surgeons.

OBJECTIVE: The objective of this study was to determine the effectiveness of a 5-minute surgical scrub using either a one-brush or a two-brush technique in clean and dirty surgical procedures, and to compare the efficacy of povidone iodine with chlorhexidine as surgical scrub solutions. STUDY DESIGN: Prospective clinical trial. METHODS: Nine veterinarians scrubbed their hands on eight separate occasions using either povidone iodine or chlorhexidine gluconate. A 5-minute scrub and either a one-brush or two-brush technique used in both clean and dirty operations were evaluated by taking glove juice samples before scrubbing, immediately after scrubbing, and 30, 60, 90, and 120 minutes after scrubbing. Glove juice samples were cultured and the colonies were counted. Percent reductions of bacterial forming units were calculated for all eight scrub procedures. RESULTS: All scrub procedures provided an adequate percent reduction in colony forming units (CFU) during the 2-hour sampling period. The number of CFU immediately after scrubbing were significantly lower than prescrub. At 120 minutes, there were significantly fewer CFUs than presecrub, but there were more than immediately after scrubbing. No significant difference in reduction in CFUs were detected between one-brush and two-brush techniques. Both chlorhexidine and povidone iodine scrub solutions adequately reduced bacterial colony counts for 120 minutes after scrubbing regardless of the amount of contamination before skin preparation. CONCLUSIONS: Bacterial counts after a hand scrub procedure using a one-brush technique were not significantly different than after a procedure that used a two-brush technique. Povidone iodine and chlorhexidine are equally effectively in decreasing bacterial numbers on the skin, given a variety of contamination levels present before the scrub procedure. CLINICAL RELEVANCE: Surgeons may use either chlorhexidine or povidone iodine for antiseptic preparation of their hands before surgery. A two-brush technique is not necessary.

Developing an effective adult nutrition screening tool for a community hospital.

OBJECTIVE: To develop a sensitive and specific nutrition screening tool that conforms to the requirements of the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and is effective in any given hospital population. DESIGN: A two-step prospective evaluation was performed in two unrelated community hospitals to determine the effectiveness of a current nutrition screening tool, and to develop a new, more sensitive tool that permits efficient use of available personnel. STATISTICAL ANALYSES: Standard calculations for sensitivity, specificity, positive predictive value, and negative predictive value were used to compare the results of various screening methods with those of full nutrition assessments. Stepwise discriminant analysis was used to determine specific parameters that contributed to the diagnosis of malnutrition and to derive a predictive equation based on these parameters. METHODS: In part 1, 100 patients admitted consecutively were evaluated using a subjective screening tool; the results were compared with those from full nutrition assessment of the same patients. Stepwise discriminant analysis identified three parameters most closely related to malnutrition, and a multivariant equation relative to nutrition risk was derived. In part 2, 151 randomly selected adult medical and surgical patients were evaluated at admission with the same screening tool used in part 1. Additionally, prealbumin level was determined on admission. The results of the screening, the discriminant analysis equation from part 1, and both methods incorporating the prealbumin level were compared with the results of a full nutrition assessment. RESULTS: In part 1, discriminant analysis identified total lymphocyte count, percentage weight loss, and serum albumin level as the three best indicators of malnutrition. A multivariant equation incorporating these objective parameters was derived. In part 2, the equation yielded better sensitivity and specificity results than other screening methods. Inclusion of prealbumin level did not improve screening methods. CONCLUSIONS: The revised screening tool described can be used as the basis of an effective screening program that meets the proposed JCAHO nutrition care standards.

Evaluation of "closed" vs "open" systems for the delivery of peptide-based enteral diets.

BACKGROUND: The study was designed to quantitate factors such as preparation time, waste, and contamination associated with three different feeding systems for peptide-based diets and to determine appropriate hang times. METHODS: Intensive care unit patients were randomized to receive a peptide-based diet in 1500-mL prefilled, sterile closed-system containers (CS) infused more than 24 hours, as open systems decanted from cans (OS-Can), or as open systems mixed from powder (OS-Powder). Open-system groups were provided a 12-hour supply twice daily in commercially clean 1-L bags with preattached sets. Samples were taken for culture during preparation and after infusion. Preparation time, initial and final microbial concentrations, and total waste were quantified. RESULTS: Preparation time was significantly shorter for CS than for OS-Can or for OS-Powder (2 minutes vs 7.5 minutes vs 13.0 minutes). Initially, 100% of the OS-Powder and 30% of the OS-Can bags were contaminated, with significant contamination exceeding 10(4) colony-forming units/mL in 40% and in 5% of the bags, respectively. On final culture, significant contamination occurred in only 2% of the CS bags compared with 83% of the OS-Powder and 60% of the OS-Can bags. Average time from potential initial contamination to final culture in CS was 49.9 hours vs 38.8 hours for OS-Can and 32 hours for OS-Powder. Total waste was greater in CS than in OS-Can or OS-Powder but could be eliminated by extending allowable hang times. CONCLUSIONS: Nonvented closed-delivery containers may be safely infused for up to 48 hours. They are associated with reduced labor and contamination.

Mapping of the active site of T7 RNA polymerase with 8-azidoATP.

The photoaffinity analog of ATP, 8-azidoATP, labels T7 RNA polymerase. Photoincorporation exhibits saturation behavior and is protected against by the substrate ATP. 8-AzidoATP is a competitive inhibitor of ATP incorporation with Ki approximately 40 microM. The photolabeled T7 RNA polymerase, following cyanogen bromide digestion, was analyzed by phenylboronate agarose column chromatography followed by reverse-phase high pressure liquid chromatography. Sequencing of the peptides labeled with radioactive photoprobe allowed the identification of three peptides, P314-M362 (I), L550-M666 (II), and F751-M861 (III). These peptides are in the proximity of the photoprobe 8-azidoATP and, therefore, expected to contain functionally significant residues and define an active site domain. These peptides (I and II) contain residues previously implicated in T7 RNA polymerase activity or show homology to active site regions of the Klenow fragment of DNA polymerase I (II and III).

Separation of bile vesicles and micelles by gel filtration chromatography: the importance of the intermicellar bile salt concentration.

Micelles and vesicles coexist in native bile. Mixed micelles are composed of bile salt, phospholipid, and cholesterol. Micellar bile salt is in equilibrium with the aqueous phase bile salt (intermicellar bile salt), and mixed micelles can be converted to cholesterol-phospholipid vesicles by depletion of bile salt. To determine the amount of cholesterol carried in vesicles and micelles, these two populations must be separated without altering the relative proportion of each. Based on the size difference between micelles and vesicles, gel filtration chromatography has been used to accomplish this separation. We reasoned that to maintain the proportion of micelles and vesicles in bile, the column must be equilibrated and eluted with buffer containing the intermicellar bile salt concentration (IMBC) and species. To test this hypothesis we created a model bile composed exclusively of micelles, a solution containing micelles and vesicles, and a model bile containing all vesicles, as demonstrated by quasielastic light scattering. Gel filtration on Sepharose 4B demonstrated that model vesicles and micelles could be separated on a column eluted with buffer containing bile salt at the IMBC. However, a modest decrease in the buffer bile salt concentration (less than 1 mmol/L) resulted in complete conversion of micelles to vesicles. A comparable increase in the buffer bile salt concentration converted vesicles to micelles. Using only taurocholate in the eluting buffer at the IMBC caused a complete shift of micelles to vesicles, whereas using only taurochenodeoxycholate resulted in conversion of vesicles to micelles. An initial collection of rat bile separated on a column equilibrated with the measured IMBC demonstrated that 94% of the cholesterol was in the micellar fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Cation radius effects on the helix-coil transition of DNA. Cryptates and other large cations.

Most polyelectrolyte theories of the effect of ions on the thermal melting of DNA assume that the predominant influence of the cations comes through their charge. Ion size and structure are treated, for analytic convenience, as negligible variables. We have examined the validity of this assumption by measuring the melting temperature of calf thymus DNA as a function of salt concentration with four univalent cations of different hydrated radii. These are K+ (3.3 A), (n-Pr)4N+ (4.5 A), (EtOH)4N+ (4.5 A), and C222-K+ (5 A). C222-K+ is a complex of cryptand C222 with K+. With K+ as the sole cation, Tm varies linearly with the log of ionic strength over the range 0.001-0.1 M. With all the K+ sequestered by an equimolar amount of C222, Tm is depressed by 10-20 degrees C and the slope of Tm vs. ionic strength is lower. At low ionic strength, an even greater reduction in Tm is achieved with (n-Pr)4N+; but the similar-sized (EtOH)4N+ gives a curve more similar to K+. Theoretical modeling, taking into account cation size through the Poisson-Boltzmann equation for cylindrical polyelectrolytes, predicts that larger cations should be less effective in stabilizing the double helix; but the calculated effect is less than observed experimentally. These results show that valence, cation size, and specific solvation effects are all important in determining the stability of the double-helical form of DNA.

The correlation between biochemical and histopathological findings in adrenoleukodystrophy.

Nine areas of the brain from a case of adrenoleukodystrophy were examined histopathologically and by gas chromatography for fatty acid content. The main findings were: (1) the degree of demyelination was related to the pentacosanoic and hexacosanoic to docosanoic acid ratios (C25:0/C22:0 and C26:0/C22:0); gliosis was related to the ratios of several fatty acids to docosanoic acid; (2) there was a shift towards smaller components (C22:0, C23:0, C24:0) of the saturated fatty acid series in the less affected areas, to larger components and various minor components in regions of active demyelination; (3) mainly saturated fatty acids of the middle class components (C24:0, C25:0 and C26:0) were found in severely affected areas where the active process is complete. Because a region of high long chain fatty acid content, lacking histopathological change, was detected, the hypothesis is presented that the primary event in childhood ALD is related to defective lipid metabolism and that this preceeds demyelination.

In vitro evidence that eukaryotic ribosomal RNA transcription is regulated by modification of RNA polymerase I.

We have utilized a cell-free transcription system from Acanthamoeba castellanii to test the functional activity of RNA polymerase I and transcription initiation factor I (TIF-I) during developmental down regulation of rRNA transcription. The results strongly suggest that rRNA transcription is regulated by modification, probably covalent, of RNA polymerase I: (1) The level of activity of TIF-I in extracts from transcriptionally active and inactive cells is constant. (2) The number of RNA polymerase I molecules in transcriptionally active and inactive cells is also constant. (3) In contrast, though the specific activity of polymerase I on damaged templates remains constant, both crude and purified polymerase I from inactive cells have lost the ability to participate in faithful initiation of rRNA transcription. (4) Polymerase I purified from transcriptionally active cells has the same subunit architecture as enzyme from inactive cells. However, the latter is heat denatured 5 times faster than the active polymerase.

Characterization of soluble polymerized fibrin formed in the presence of excess fibrinogen fragment D.

Polymerization of fibrin is inhibited in the presence of excess fibrinogen fragment D. This study was performed in order to test the proposal that these inhibited solutions contain short linear polymers of fibrin (protofibrils) whose further polymerization is prevented as a result of attachment of a molecule of fragment D at each end. Negative-stain electron micrographs, intrinsic viscosities, angular dependence of light scattering intensity, and kinetics of the increase of the scattered intensity with polymerization all were found to support the above model of the inhibited polymer and to reflect the presence of a broad distribution of the lengths of the inhibited fibrin polymers. Furthermore, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of polymers stabilized with gamma-dimer cross-links introduced by factor XIIIa demonstrates cross-linking of fragment D to fibrin oligomers. Cross-linked polymers have been separated from excess fragment D by gel exclusion chromatography in 1 M urea. (In the absence of urea, the purified polymers very slowly associate to fibers.) The observation of the relative stability of short isolated inhibited protofibrils and the decrease or absence of inhibition of fibrin gelation when fragment D was added to solutions in which fibrin had been given time to polymerize to long protofibrils demonstrate that the inhibitory effect of fragment D occurs as a result of inhibition of the first fibrin polymerization step.