Serrated adenoma of the colorectum

An understanding of the pathology and natural history of serrated adenoma of the colorectum has emerged slowly and comparatively recently. In this review, hyperplastic polyps, admixed polyps and serrated adenomas are conceived as a continuum of serrated polyps. Mechanisms underlying the expression of serrated morphology are outlined. The demographic, macroscopic and microscopic features of serrated adenoma are presented but it is stressed that the distinction from other epithelial polyps may not always be straightforward. Molecular studies point to heterogeneity within the serrated pathway and among conditions encompassed by the term serrated polyposis. Management of serrated adenoma is discussed but the need for further research is emphasized. The importance of serrated adenoma as a precancerous lesion has been underestimated. © 2002 Elsevier Science Ltd.

Quinolizine-2,4-diones by reversible dimerisation 2-pyridylketenes

Quinolizine-2,4-diones 11 are obtained by ash vacuum thermolysis (FVT) of 3-acyl-1,2,3-triazolo[1,5-a]pyridines 7. The reaction takes place via methyl- and phenyl(2-pyridyl)ketenes 10, which are directly observable by infrared spectroscopy in low temperature matrices. FVT of 11 regenerates the ketenes 10.

Convergent maternal care strategies in ungulates and macropods

Mammals show extensive interspecific variation in the form of maternal care. Among ungulates, there is a dichotomy between species in which offspring follow the mother (following strategy) versus species in which offspring remain concealed (hiding strategy). Here we reveal that the same dichotomy exists among macropods (kangaroos, wallabies and allies). We test three traditional adaptive explanations and one new life history hypothesis. and find very similar patterns among both ungulates and macropods. The three traditional explanations that we tested were that a ''following'' strategy is associated with (1) open habitat, (2) large mothers, and (3) gregariousness. Our new life-history hypothesis is that a following strategy'' is associated with delayed weaning, and thus with the slow end of the slow-fast mammalian life-history continuum, because offspring devote resources to locomotion rather than rapid growth. Our comparative test strongly supports the habitat structure hypothesis and provides some support for this new delayed weaning hypothesis for both ungulates and macropods. We propose that sedentary young in closed habitats benefit energetically by having milk brought to them. In open habitats, predation pressure will select against hiding. Followers will suffer slower growth to independence. Taken together, therefore, our results provide the first quantitative evidence that macropods and ungulates are convergent with respect to interspecific variation in maternal care strategy. In both clades, differences between species in the form of parental care are due to a similar interaction between habitat, social behavior, and life history.

The radiation chemistry of ultem at 77 K as revealed by ESR spectroscopy

Radical formation in ultem following gamma-radiolysis has been reassessed, and the G(R*) values at different temperatures have been determined by ESR spectroscopy. The radical assignment and radical reactivity have been re-examined by photobleaching and thermal annealing studies. Photobleachable radical anions were found to comprise approximate to40% of the total number of radicals formed on radiolysis at 77 K. Spectral subtraction methods, ESR spectral simulations, measurement of g-values and the hyperfine splitting constants were used to identify the other radical intermediates. The principal chain scission radicals are formed due to scission of the main-chain at (i) the ether linkage, (ii) the isopropylidene group and (iii) the imide ring in the main chain. The side chain methyl groups of the isopropylidine units also lose hydrogen to form methylene radicals. The five-line spectrum observed to decay in the temperature range 370-430 K, which has not been assigned previously, has been identified as being characteristic of a di-substituted benzyl radical. (C) 2002 Elsevier Science Ltd. All rights reserved.

The copolymerization of N-vinyl-2-pyrrolidone with 2-hydroxyethyl methacrylate

The bulk free radical copolymerization of 2-hydroxyethyl methacrylate (HEMA) with N-vinyl-2-pyrrolidone (VP) was carried out to low conversions at 50 degreesC, using benzoyl peroxide (BPO) as initiator. The compositions of the copolymers; were determined using C-13 NMR spectroscopy. The conversion of monomers to polymers was studied using FT-NIR spectroscopy in order to predict the extent of conversion of monomer to polymer. From model fits to the composition data, a statistical F-test revealed that die penultimate model describes die copolymerization better than die terminal model. Reactivity ratios were calculated by using a non-linear least squares analysis (NLLS) and r(H) = 8.18 and r(V) = 0.097 were found to be the best fit values of the reactivity ratios for the terminal model and r(HH) = 12.0, r(VH) = 2.20, r(VV) = 0.12 and r(HV) = 0.03 for the penultimate model. Predictions were made for changes in compositions as a function of conversion based upon the terminal and penultimate models.

From molecular complexes to zwitterions and final products. Reactions between C3O2 and amines

The formation of molecular complexes (prereactive intermediates) between C3O2 and amines (ammonia, dimethylamine, trimethylamine, and 4-(dimethylamino)pyridine) as well as the subsequent transformation of the complexes into C3O2-amine zwitterions in cryogenic matrixes (ca. 40 K) has been observed. In the case of dimethylamine, the formation of tetramethylmalonamide has also been documented. Calculations using density functional theory (B3LYP/6-31G(2d, p)) are used to assign all above species and are in excellent agreement with the IR spectra.

Inhibition of tubulin assembly and covalent binding to microtubular protein by valproic acid glucuronide in vitro

Acyl glucuronides are reactive metabolites of carboxylate drugs, able to undergo a number of reactions in vitro and in vivo, including isomerization via intramolecular rearrangement and covalent adduct formation with proteins. The intrinsic reactivity of a particular acyl glucuronide depends upon the chemical makeup of the drug moiety. The least reactive acyl glucuronide yet reported is valproic acid acyl glucuronide (VPA-G), which is the major metabolite of the antiepileptic agent valproic acid (VPA). In this study, we showed that both VPA-G and its rearrangement isomers (iso-VPA-G) interacted with bovine brain microtubular protein (MTP, comprised of 85% tubulin and 15% microtubule associated proteins {MAPs}). MTP was incubated with VPA, VPA-G and iso-VPA-G for 2 h at room temperature and pH 7.5 at various concentrations up to 4 mM. VPA-G and iso-VPA-G caused dose-dependent inhibition of assembly of MTP into microtubules, with 50% inhibition (IC50) values of 1.0 and 0.2 mM respectively, suggesting that iso-VPA-G has five times more inhibitory potential than VPA-G. VPA itself did not inhibit microtubule formation except at very high concentrations (greater than or equal to2 mM). Dialysis to remove unbound VPA-G and iso-VPA-G (prior to the assembly assay) diminished inhibition while not removing it. Comparison of covalent binding of VPA-G and iso-VPA-G (using [C-14]-labelled species) showed that adduct formation was much greater for iso-vTA-G. When [C-14]-iso-VPA-G was reacted with MTP in the presence of sodium cyanide (to stabilize glycation adducts), subsequent separation into tubulin and MAPs fractions by ion exchange chromatography revealed that 78 and 22% of the covalent binding occurred with the MAPs and tubulin fractions respectively. These experiments support the notion of both covalent and reversible binding playing parts in the inhibition of microtubule formation from MTP (though the acyl glucuronide of VPA is less important than its rearrangement isomers in this regard), and that both tubulin and (perhaps more importantly) MAPs form adducts with acyl glucuronides. (C) 2002 Elsevier Science Inc. All rights reserved.

Development of the HIV/AIDS stress scale

Development of a self-report measure of stress specific to HIV/AIDS is needed to advance our understanding of the role of stress in adaptation to HIV/AIDS: hence, the aim of this study was the development of the HIV/AIDS Stress Scale. A total of 132 homosexual/bisexual men with HIV/AIDS v ere interviewed and completed the HIV/AIDS Stress Scale and measures of coping strategies, appraisal, social support and adjustment (global distress, depression, social adjustment, number of HIV symptoms, and subjective health status) at three time points. Thirty-nine primary caregivers were interviewed and completed measures of stress and adjustment. Exploratory factor analyses of the HIV/AIDS Stress Scale items revealed three factors: Social, Instrumental and Emotional/Existential Stress. Factors had adequate internal reliabilities and were stable over 12 months. Construct validation data are consistent with recent stress/coping research that links higher levels of stress with more HIV symptoms. reliance on emotion-focused coping, lower social support, poorer levels of adjustment and higher levels of caregiver stress. Results extend this research by revealing new differential relations between various stress dimensions and stress/coping variables. Convergent validation data suggest that the HIV/AIDS Stress Scale shares conceptual similarity with threat appraisal. and differs from control liability and challenge appraisals. The HIV/AIDS Stress Scale shows potential for the elucidation of the role of stress in coping and adaptation to HIV/AIDS and disease progression in both research and clinical applications.

The efficacy of a psychosocial intervention for HIV/AIDS caregiving dyads and individual caregivers: a controlled treatment outcome study

The present study examined the comparative efficacy of intervening at the caregiver/care-recipient dyadic level, versus the individual caregiver level, for caregivers and their care-recipients with HIV/AIDS. Participants were randomly assigned to a Dyad Intervention (DI), a Caregiver Intervention (CI) or Wait List Control group (WLC), and assessed by interview and self-administered scales immediately before treatment and eight weeks later. Participants in the intervention groups also completed a four-month follow-up assessment. Dependent variables included global distress, social adjustment, dyadic adjustment, subjective health status, HIV/AIDS knowledge and target problem ratings. Results showed that caregivers in the DI group showed greater improvement from pre- to post-treatment on global distress, dyadic adjustment and target problems than the CI and WLC caregivers. The CI and DI caregivers showed greater improvement than the WLC group on all dependent variables except social adjustment. Care-recipients in the DI group improved significantly from pre- to post-treatment on dyadic adjustment, social adjustment, knowledge, subjective health status and Target Problem 1, whereas the CI and WLC care-recipients failed to improve on any of these measures. The treatment gains made by the DI caregivers and care-recipients on most dependent variables were maintained at a four-month follow-up. Findings support a reciprocal determinism approach to the process of dyadic adjustment and suggest that intervening at the caregiver/care-recipient level may produce better outcomes for both the caregiver and care-recipient than intervening at the individual caregiver level.

A cassette ligation strategy with thioether replacement of three Gly-Gly peptide bonds: Total chemical synthesis of the 101 residue protein early pregnancy factor [psi(CH2S)(28-29,56-57,76-77)]

The 101 residue protein early pregnancy factor (EPF), also known as human chaperonin 10, was synthesized from four functionalized, but unprotected, peptide segments by a sequential thioether ligation strategy. The approach exploits the differential reactivity of a peptide-NHCH2CH2SH thiolate with XCH2CO-peptides, where X = Cl or I/Br. Initial model studies with short functionalized (but unprotected) peptides showed a significantly faster reaction of a peptide-NHCH2CH2SH thiolate with a BrCH2CO-peptide than with a CICH2CO-peptide, where thiolate displacement of the halide leads to chemoselective formation of a thioether surrogate for the Gly-Gly peptide bond. This rate difference was used as the basis of a novel sequential ligation approach to the synthesis of large polypeptide chains. Thus, ligation of a model bifunctional N-alpha-chloroacetyl, C-terminal thiolated peptide with a second N-alpha-bromoacetyl peptide demonstrated chemoselective bromide displacement by the thiol group. Further investigations showed that the relatively unreactive N-alpha-chloroacetyl peptides could be activated by halide exchange using saturated KI solutions to yield the highly reactive No-iodoacetyl peptides. These findings were used to formulate a sequential thioether ligation strategy for the synthesis of EPF, a 101 amino acid protein containing three Gly-Gly sites approximately equidistantly spaced within the peptide chain. Four peptide segments or cassettes comprising the EPF protein sequence (BrAc-[EPF 78-101] 12, ClAc-[EPF 58-75]-[NHCH2CH2SH] 13, ClAc-[EPF 30-55]-[NHCH2CH2SH] 14, and Ac-[EPF 1-27]-[NHCH2CH2SH] 15) of EPF were synthesized in high yield and purity using Boc SPPS chemistry. In the stepwise sequential ligation strategy, reaction of peptides 12 and 13 was followed by conversion of the N-terminal chloroacetyl functional group to an iodoacetyl, thus activating the product peptide for further ligation with peptide 14. The process of ligation followed by iodoacetyl activation was repeated to yield an analogue of EPF (EPF psi(CH2S)(28-29,56-57,76-77)) 19 in 19% overall yield.

On the intrinsic capacity for increase of Australian flying-foxes (Pteropus spp., Megachiroptera)

In the reproductive biology of organisms, a continuum exists from "highly reproductive species" at one end to "survivor species" at the other end. Among other factors, the position of a species along this continuum affects its sensitivity to human exploitation and its vulnerability to extinction. Flying foxes are long-lived, seasonal breeders, with a rigid, well-defined breeding season that is largely or wholly genetically determined. Unlike opportunistic, highly reproductive species, such as rabbits or mice, female flying foxes are unable to produce viable young before their second or third year of life, and are then capable of producing just one young per year. Such a breeding strategy will be successful only if flying-foxes are long-lived and suffer naturally low mortality rates. In this paper, we assess the vulnerability of flying foxes to extinction, using basic parameters of reproduction observed in the wild, and in captive breeding colonies of P. poliocephalus, P. alecto and P. scapulatus, and survival rates that are likely to apply to Australian conditions. Our models show explicitly that flying-fox populations have a very low capacity for increase, even under the most ideal conditions. The implications of our models are discussed in reference to the long-term management and conservation needs of Australian flying foxes. We conclude that current death-rates of flying-foxes in NSW and Queensland fruit orchards are putting state populations at serious risk.

Predicting cave initiation and propagation

The most widely used method for predicting the onset of continuous caving is Laubscher's caving chart. A detailed examination of this method was undertaken which concluded that it had limitations which may impact on results, particularly when dealing with stronger rock masses that are outside current experience. These limitations relate to inadequate guidelines for adjustment factors to rock mass rating (RMR), concerns about the position on the chart of critical case history data, undocumented changes to the method and an inadequate number of data points to be confident of stability boundaries. A review was undertaken on the application and reliability of a numerical method of assessing cavability. The review highlighted a number of issues, which at this stage, make numerical continuum methods problematic for predicting cavability. This is in particular reference to sensitivity to input parameters that are difficult to determine accurately and mesh dependency. An extended version of the Mathews method for open stope design was developed as an alternative method of predicting the onset of continuous caving. A number of caving case histories were collected and analyzed and a caving boundary delineated statistically on the Mathews stability graph. The definition of the caving boundary was aided by the existence of a large and wide-ranging stability database from non-caving mines. A caving rate model was extrapolated from the extended Mathews stability graph but could only be partially validated due to a lack of reliable data.

Kinetic parameters associated with self-heating of New Zealand coals under adiabatic conditions

Adiabatic self-heating tests were carried out on five New Zealand coal samples ranging in rank from lignite to high-volatile bituminous. Kinetic parameters of oxidation were obtained front the self-heating curves assuming Arrhenius behaviour. The activation energy E (kJ mol(-1)) and the pre-exponential factor A (s(-1)) were determined in the temperature range of 70-140 degreesC. The activation energy exhibited a definite rank relationship with a minimum E of 55 kJ mol(-1) occurring at a Suggate rank of similar to6.2 corresponding to subbituminous C. Either side of this rank there was a noticeable increase in the activation energy indicating lower reactivity of the coal. A similar rank trend was also observed in the R-70 self-heating rate index values that were taken from the initial portion of the self-heating curve front 40 to 70 degreesC. From these results it is clear that the adiabatic method is capable of providing reliable kinetic parameters of coal oxidation.

A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention

PURPOSE: To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and Symptom status in patients with symptomatic coronary artery disease. METHODS: Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a, more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function.(brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION: Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden. Am J Med. 2003;114:445-453. (C) 2003 by Excerpta Medica Inc.