Comparison of the management and in-hospital outcomes of acute coronary syndrome patients in Australia and New Zealand: results from the binational SNAPSHOT acute coronary syndrome 2012 audit.

BACKGROUND/AIMS: We aimed to assess differences in patient management, and outcomes, of Australian and New Zealand patients admitted with a suspected or confirmed acute coronary syndrome (ACS). METHODS: We used comprehensive data from the binational Australia and New Zealand ACS 'SNAPSHOT' audit, acquired on individual patients admitted between 00.00 h on 14 May 2012 to 24.00 h on 27 May 2012. RESULTS: There were 4387 patient admissions, 3381 (77%) in Australia and 1006 (23%) in New Zealand; Australian patients were slightly younger (67 vs 69 years, P = 0.0044). Of the 2356 patients with confirmed ACS, Australian patients were at a lower cardiovascular risk with a lower median Global Registry Acute Coronary Events score (147 vs 154 P = 0.0008), but as likely to receive an invasive coronary angiogram (58% vs 54%, P = 0.082), or revascularisation with percutaneous coronary intervention (32% vs 31%, P = 0.92) or coronary artery bypass graft surgery (7.0% vs 5.6%, P = 0.32). Of the 1937 non-segment elevation myocardial infarction/unstable angina pectoris (NSTEMI/UAP) patients, Australian patients had a shorter time to angiography (46 h vs 67 h, P < 0.0001). However, at discharge, Australian NSTEMI/UAP survivors were less likely to receive aspirin (84% vs 89%, P = 0.0079, a second anti-platelet agent (57% vs 63%, P = 0.050) or a beta blocker (67% vs 77%, P = 0.0002). In-hospital death rates were not different (2.7% vs 3.2%, P = 0.55) between Australia and New Zealand. CONCLUSIONS: Overall more similarities were seen, than differences, in the management of suspected or confirmed ACS patients between Australia and New Zealand. However, in several management areas, both countries could improve the service delivery to this high-risk patient group.

Patterns of inflammatory activation associated with precipitants of acute coronary syndromes: a case-crossover study.

AIMS: We sought to assess a broad array of possible precipitants of acute coronary syndromes (ACS) and evaluate their association with detectable inflammatory activation. METHODS AND RESULTS: Within a case-crossover design, using a standardised questionnaire, interviews among 348 ST-elevation myocardial infarction (44%) or high-risk non-ST-elevation ACS patients (56%), explored potential precipitants, including: infection (INF)-temperature >38°C and/or respiratory tract, urinary or skin infection; inflammation (INFL)-exacerbation of inflammatory conditions; exercise (EX)-moderate to heavy exercise; fast food (FF)-consumption of a meal purchased from a fast food company. Risk and control periods were: weekly over 8 weeks for INF and INFL; 24 hourly over 4 days for FF and 4 hourly over 48 h for EX. C-reactive protein (CRP) levels were assessed at admission. These precipitants were identified in 203/348 (58.3%) patients. An increased temporal risk was observed for: INF (0-7 days vs 7-8 weeks odds ratio (OR): 7.5, confidence interval (CI): 1.7-67.6, P = 0.002); INFL (0-7 days vs 7-8 weeks OR: 14.0, CI: 2.13-591.9, P = 0.001); EX (0-4 h vs 24-28 h OR: 2.2, CI: 1.3-3.5, P = 0.001) and FF (0-24 h vs 72-96 h OR: 5.67, CI: 1.6-30.2, P = 0.003). CRP levels were significantly elevated among patients reporting infective and inflammatory potential precipitants, but not among those reporting fast food consumption and unaccustomed moderate-heavy exercise. CONCLUSION: Infection, inflammatory conditions, moderate-heavy exercise and potentially fast food consumption appear to precipitate high-risk ACS. Increased inflammation as measured by CRP was not consistently detected despite the identification of an ACS precipitant. Strategies that target improved overall health may also lead to fewer ACS events through a reduction in triggers.

Predictors of engagement with remote sensing technologies for symptom measurement in Major Depressive Disorder.

BACKGROUND: Remote sensing for the measurement and management of long-term conditions such as Major Depressive Disorder (MDD) is becoming more prevalent. User-engagement is essential to yield any benefits. We tested three hypotheses examining associations between clinical characteristics, perceptions of remote sensing, and objective user engagement metrics. METHODS: The Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) study is a multicentre longitudinal observational cohort study in people with recurrent MDD. Participants wore a FitBit and completed app-based assessments every two weeks for a median of 18 months. Multivariable random effects regression models pooling data across timepoints were used to examine associations between variables. RESULTS: A total of 547 participants (87.8% of the total sample) were included in the current analysis. Higher levels of anxiety were associated with lower levels of perceived technology ease of use; increased functional disability was associated with small differences in perceptions of technology usefulness and usability. Participants who reported higher system ease of use, usefulness, and acceptability subsequently completed more app-based questionnaires and tended to wear their FitBit activity tracker for longer. All effect sizes were small and unlikely to be of practical significance. LIMITATIONS: Symptoms of depression, anxiety, functional disability, and perceptions of system usability are measured at the same time. These therefore represent cross-sectional associations rather than predictions of future perceptions. CONCLUSIONS: These findings suggest that perceived usability and actual use of remote measurement technologies in people with MDD are robust across differences in severity of depression, anxiety, and functional impairment.

Kinetic studies on the adsorption of Cd2+, Cu2+ and Zn2+ ions from aqueous solutions by cassava (Manihot sculenta Cranz) tuber bark waste.

The kinetics of Cd2+, Cu2+ and Zn2+ adsorption onto pure and thioglycolic acid treated cassava tuber bark wastes (CTBW) were investigated using a batch sorption technique at 30 degrees C. Kinetic data suggested that the adsorption process was exothermic, the rate limiting sorption step was physisorption and adsorption rates could be best described by a pseudo-second order model. Rate coefficients were determined to range between 1.39x10(-2)min(-1) and 5.94x10(-2)min(-1), 1.46x10(-3)min(-1) and 5.76x10(-3)min(-1) and 0.69x10(-3)min(-1) and 5.8x10(-3)min(-1) for Cd2+, Cu2+ and Zn2+, respectively. The results from these studies indicated that the sorption process is fast and stable. The adsorption equilibria were evaluated using the Langmuir equation and the monolayer sorption capacity was found to range between 5.88-26.3mg/g, 33.3-90.9 mg/g and 22.2-83.3mg/g for Cd2+, Cu2+ and Zn2+, respectively. Negative values of DeltaG(ads)(0) indicated that the adsorption process was spontaneous and exothermic in nature.

Accuracy of replication past the T-C (6-4) adduct.

The thymine-cytosine pyrimidine-pyrimidone (6-4) adduct has variously been predicted to be among the most and among the least mutagenic of the ultraviolet light photoproducts. We have therefore investigated the frequency and accuracy of DNA replication past this lesion, using a single-stranded M13mp7-based vector with a uniquely located example of this lesion transfected into SOS-induced and uninduced cells of a uvr A6 strain of Escherichia coli. Both the UVC T-C (6-4) adduct and its Dewar valence (UVB) photoisomer were studied. Random samples from non-selective collections of progeny phage were sequenced to determine the nature of the replication events that occurred at or near the site of template damage under SOS conditions. The UVC (6-4) adduct was found to be much less mutagenic than its T-T counterpart, but still much more mutagenic than a cyclobutane dimer; 34% (71 out of 206) of all bypass events yielded mutations, of which all were targeted and 80% (57 out of 71) were 3' C-->T transitions. The Dewar valence photoisomer exhibited reduced specificity and enhanced mutagenicity; 79% (183 out of 233) of the phage progeny were mutants, of which all but one were targeted and 45% (83 out of 183) were 3' C-->T transitions. For the most part, these results are consistent with a model postulating base-pairing between the pyrimidinone (of either the C or T variety) and guanine, via hydrogen bonds at N-3 and O-2 in the UVC, but not the Dewar, isomer. The occurrence of the 3' C-->T transitions, not predicted by this model, shows however that the absence of a methyl group at C-5 also has a significant influence on mutation induction. Both isomers were efficient blocks to replication; less than 1% of these vectors could be replicated in uninduced cells. Following SOS induction the frequency of bypass increased to 24.5% and 12.5% for the UVC and the Dewar isomers, respectively.

Defect in excision repair alters the mutational specificity of PUVA treatment in the lacI gene of Escherichia coli.

The sequences of 152 lacI- mutations obtained following exposure of Escherichia coli UvrB- strain NR3951 to ultraviolet light in the presence of 8-methoxypsoralen (PUVA treatment) were compared to the spectrum of mutation induced by PUVA treatment in a Uvr+ strain, NR3835. Mutations recovered following PUVA treatment of the UvrB- strain were quite different from those recovered in the Uvr+ strain. In addition, they occurred at a restricted number of unique sites. For example, A.T----T.A base substitutions at position 141, minus G frameshifts at positions 586/587/588 and deletions of 15 base-pairs from position 78 to 92 accounted for 50% or more of mutations recovered in each of the above mutational classes. This altered mutational specificity was accompanied by a failure to recover mutations frequently identified following PUVA treatment of the Uvr+ strain. These mutations include spontaneous-hotspot frameshifts involving the gain or loss of a tetramer 5'-CTGG-3' repeated three times at position 620 to 631; and minus A.T base-pair frameshifts recovered at potential T-T crosslink sites. These results indicate that while crosslinks may play a substantial role in the induction of mutation in the Uvr+ strain, they do not contribute substantially to mutagenesis in the UvrB- strain. In addition, the data also suggest that excision repair may not always occur in an error-free manner.

Missense mutation in the lacI gene of Escherichia coli. Inferences on the structure of the repressor protein.

The lac repressor has been studied extensively but a precise three-dimensional structure remains unknown. Studies using mutational data can complement other information and provide insight into protein structure. We have been using the lacI gene-repressor protein system to study the mutational specificity of spontaneous and induced mutation. The sequencing of over 6000 lacI- mutations has revealed 193 missense mutations generating 189 amino acid replacements at 102 different sites within the lac repressor. Replacement sites are not distributed evenly throughout the protein, but are clustered in defined regions. Almost 40% of all sites and over one-half of all substitutions found occur within the amino-terminal 59 amino acid residues, which constitute the DNA-binding domain. The core domain (residues 60 to 360) is less sensitive to amino acid replacement. Here, substitution is found in regions involved in subunit aggregation and at sites surrounding residues that are implicated in sugar-binding. The distribution and nature of missense mutational sites directs attention to particular amino acid residues and residue stretches.

Monoclonal antibody BB9 raised against bone marrow stromal cells identifies a cell-surface glycoprotein expressed by primitive human hemopoietic progenitors.

OBJECTIVE: The identification of cell-surface antigens whose expression is limited to primitive hematopoietic progenitor cells (HPC) is of major value in the identification, isolation, and characterization of candidate stem cells in human hemopoietic tissues. Based on the observation that bone marrow stromal cells and primitive HPC share several cell-surface antigens, we sought to generate monoclonal antibodies to HPC by immunization with cultured human stromal cells. METHODS: BALB/c mouse were immunized with human bone marrow (BM)-derived stromal cells. Splenocytes isolated from immunized mice were fused with the NS-1 murine myeloma cell line and resulting hybridomas selected in HAT medium, then screened for reactivity against stromal cells, peripheral blood (PB), and BM cells. RESULTS: A monoclonal antibody (MAb), BB9, was identified based on its binding to stromal cells, a minor subpopulation of mononuclear cells in adult human BM, and corresponding lack of reactivity with leukocytes in PB. BB9 bound to a minor subpopulation of BM CD34(+) cells characterized by high-level CD34 antigen and Thy-1 expression, low-absent expression of CD38, low retention of Rhodamine 123, and quiescent cycle status as evidenced by lack of labeling with Ki67. CD34(+)BB9(+) cells, in contrast to CD34(+)BB9(-) cells, demonstrated a capacity to sustain hematopoiesis in pre-CFU culture stimulated by the combination of IL-3, IL-6, G-CSF, and SCF. BB9 also demonstrated binding to CD34(+) cells from mobilized PB. CONCLUSION: Collectively, these data therefore demonstrate that MAb BB9 identifies an antigen, which is selectively expressed by hierarchically primitive human HPC and also by stromal cells.

Nearest neighbor affects G:C to A:T transitions induced by alkylating agents.

The influence of local DNA sequence on the distribution of G:C to A:T transitions induced in the lacI gene of E. coli by a series of alkylating agents has been analyzed. In the case of nitrosoguanidine, two nitrosoureas and a nitrosamine, a strong preference for mutation at sites proceeded 5' by a purine base was noted. This preference was observed with both methyl and ethyl donors where the predicted common ultimate alkylating species is the alkyl diazonium ion. In contrast, this preference was not seen following treatment with ethylmethanesulfonate. The observed preference for 5'PuG-3' site over 5'-PyG-3' sites corresponds well with alterations observed in the Ha-ras oncogene recovered after treatment with NMU. This indicates that the mutations recovered in the oncogenes are likely the direct consequence of the alkylation treatment and that the local sequence effects seen in E. coli also appear to occur in mammalian cells.

Mutational specificity of alkylating agents and the influence of DNA repair.

Alkylating treatments predominantly induce G: C = greater than A:T transitions, consistent with the predicted significance of the miscoding potential of the O6-alG lesion. However, the frequency and distribution of these events induced by any one compound may be diagnostic. SN1 agents that act via an alkyldiazonium cation, such as the N-nitroso compounds, preferentially generate G: C = greater than A:T transitions at 5'-RG-3' sites, while the more SN2 alkylsulfates and alkylalkane-sulfonates do not. The precise nature of this site bias and the possibility of strand bias are target dependent. The extent of this site bias and the contribution of other base substitutions are substituent size dependent. A similar 5'-RT-3' effect is seen for A:T = greater than G:C transitions, presumably directed by O4-alT lesions. The 5'-RG-3' effect, at least, likely reflects a deposition specificity arising from some aspect of helix geometry, although it may be further exaggerated by alkylation-specific repair. Excision repair appears to preferentially reduce the occurrence of ethylation-induced G:C = greater than A:T and A:T = greater than G:C transitions at sites flanked by A:T base pairs. This may be due to an enhancement of the helical distortion imposed by damage at such positions. A similar effect is not seen for methylation-induced mutations and in the case of propyl adducts, the influence of excision repair on the ultimate distribution of mutation cannot be as easily defined with respect to neighbouring sequence.

Mutational specificity of thymine deprivation-induced mutation in the lacI gene of Escherichia coli.

LacI- mutants obtained following 2 and 6 h of thymine deprivation were cloned and sequenced. The mutational spectra recovered were dissimilar. After 2 h of starvation the majority of mutations were base substitutions, largely G:C----C:G transversions. Frameshift mutations but not deletions were observed. In contrast, following 6 h of starvation, with the exception of the G:C----C:G transversion, all possible base substitutions were recovered. Moreover, several deletions but no frameshift events were observed. The differences in the mutational spectra recovered after the two periods of thymine deprivation highlight the role of altered nucleotide pools and the potential influence of DNA replication and repair mechanisms.

Mutagenesis induced by single UV photoproducts in E. coli and yeast.

Data from experiments with single-stranded vectors that carry a site-specific cyclobutane dimer, pyrimidine (6-4) pyrimidone adduct, or abasic lesion, replicated in either E. coli or, in some cases, bakers' yeast, Saccharomyces cerevisiae, are used to examine two questions: (i) what factors are responsible for the lesion's mutagenicity? and (ii) what are the relative contributions of different photoproducts to the spectrum of UV-induced mutations? With respect to the first question, we suggest that the structure of the mutagen-modified template itself largely determines the kinds of mutations induced, but the relative frequencies of these mutations, the error frequency, and the bypass frequency are strongly dependent on the particular organism studied. With respect to the second question, we suggest that cyclobutane dimers may be responsible for most of the mutations in slowly replicating genomes because of the deamination of cytosine, and that the T-T, and to a lesser extent the T-C, (6-4) adducts play a greater role in the UV mutagenesis of quickly replicating viruses, such as M13 and lambda phage.

Sorption of cadmium(II) and zinc(II) ions from aqueous solutions by cassava waste biomass (Manihot sculenta Cranz).

The sorption of two divalent metal ions, Cd(II) and Zn(II), onto untreated and differentially acid-treated cassava waste biomass over a wide range of reaction conditions was studied at 30 degrees C. The metal ion removal from the spent biomass was also measured. The batch experiments show that pH 4.5-5.5 was the best range for the sorption of the metal ions for untreated and acid-treated biomass. Time-dependent experiments for the metal ions showed that for the two metals examined, binding to the cassava waste biomass was rapid and occurred within 30 min and completed within 1h. High sorption capacities were observed for the two metals. The binding capacity experiments revealed the following amounts of metal ions bound per gram of biomass: 86.68 mg/g Cd, 55.82 mg/g Zn and 647.48 mg/g Cd, 559.74 mg/g Zn for untreated and acid-treated biomass, respectively. It was further found that the rate of sorption was particle-diffusion controlled, and the sorption rate coefficients were determined to be 2.30 x 10(-1)min(-1) (Cd(2+)), 4.0 x 10(-3)min(-1) (Zn(2+)) and 1.09 x 10(-1)min(-1) (Cd(2+)), 3.67 x 10(-2)min(-1) (Zn(2+)) for 0.5 and 1.00 M differential acid treatment, respectively. Desorption studies showed that acid treatment inhibited effective recovery of metal ions already bound to the biomass as a result of stronger sulfhydryl-metal bonds formed. Less than 25% of both metals were desorbed as concentration of acid treating reagent increases. However, over 60% Cd and 40% Zn were recovered from untreated biomass during the desorption study. The results from these studies indicated that both untreated and acid-treated cassava waste biomass could be employed in the removal of toxic and valuable metals from industrial effluents.

The use of chemically modified and unmodified cassava waste for the removal of Cd, Cu and Zn ions from aqueous solution.

The use of different chemically modified cassava waste biomass for the enhancement of the adsorption of three metal ions Cd, Cu and Zn from aqueous solution is reported in this paper. Treating with different concentrations of thioglycollic acid modified the cassava waste biomass. The sorption rates of the three metals were 0.2303 min(-1) (Cd(2+)), 0.0051 min(-1) (Cu(2+)), 0.0040 min(-1) (Zn(2+)) and 0.109 min(-1) (Cd(2+)), 0.0069 min(-1) (Cu(2+)), 0.0367 min(-1) (Zn(2+)) for 0.5 and 1.00 M chemically modified levels, respectively. The adsorption rates were quite rapid and within 20-30 min of mixing, about 60-80% of these ions were removed from the solutions by the biomass and that chemically modifying the binding groups in the biomass enhanced its adsorption capacity towards the three metals. The results further showed that increased concentration of modifying reagent led to increased incorporation, or availability of more binding groups, in the biomass matrix, resulting in improved adsorptivity of the cassava waste biomass. The binding capacity study showed that the cassava waste, which is a serious environmental nuisance, due to foul odour released during decomposition, has the ability to adsorb trace metals from solutions.

Changing patterns in the use of slow acting antirheumatic drugs for the treatment of rheumatoid arthritis.

AIM: To report on the changing use of slow acting antirheumatic drugs in the treatment of rheumatoid arthritis by contrasting prescribing patterns in 1990 and 1995. METHOD: Data were extracted from the case notes of 103 outpatients with rheumatoid arthritis. Results were compared with those obtained in 1990 in a survey of 81 patients using identical methods. RESULTS: There was a significant increase in the use of methotrexate between 1990 and 1995, and a marked decrease in the use of auranofin. A new feature was the use of drugs in combination. Methotrexate was the most effective agent and auranofin least effective (p = 0.02). The agent with the highest average toxicity score was D-penicillamine. The long term tolerability of methotrexate was superior, with a median time for remaining on therapy 6.4 times longer than that of the other slow acting antirheumatic drugs (p = 0.01). CONCLUSIONS: Our results suggest that identified trends in the altered use of slow acting antirheumatic drugs for treatment of rheumatoid arthritis are rationally based on the increased use of the most effective agents and decreased use of those with greater toxicity and lesser efficacy.

Mutation site specificity of N-nitroso-N-methyl-N-alpha-acetoxybenzylamine: a model derivative of an esophageal carcinogen.

A total of 171 mutations induced by N-nitroso-N-methyl-N-alpha-acetoxybenzylamine within the first 180 base pairs of the lacI gene of Escherichia coli were characterized at the DNA sequence level. Consistent with the methylating ability of this compound and the predicted mutagenic specificity of the O6-methylguanine lesion, all but two of these mutations were G:C----A:T transitions. An analysis of neighboring sequences revealed the same 5' flanking sequence influence on mutability reported for other SN1-type direct-acting alkylating agents. G:C----A:T transitions were found to be six times more likely to occur at G:C base pairs at which the guanine residues were flanked (5') by a purine than at those preceded by a pyrimidine. This mutagenic and site specificity appeared to be independent of the dose and likely reflects the behaviour of the activated parent carcinogen, N-nitroso-N-methyl-N-benzylamine in the esophagus.

Mutational specificities of environmental carcinogens in the lacI gene of Escherichia coli. I. The direct-acting analogue N-nitroso-N-methyl-N-alpha-acetoxymethylamine.

The mutational specificity of N-nitroso-N-methyl-N-alpha-acetoxymethylamine in Escherichia coli has been determined through the DNA sequence characterization of 190 forward mutations in the lacI gene. Consistent with the methylating ability of this compound and the predicted mutagenic potential of O6-methylguanine damage, the predominant mutation was the G:C----A:T transition. An analysis of the neighbouring template revealed a similar 5' flanking sequence influence on G:C----A:T site mutability reported for other direct-acting SN1 alkylating agents. However, a dose-dependency was observed. The preference for transition at guanine residues flanked (5') by a purine over those preceded by a pyrimidine decreased from a ratio of 19:1 (upon 1 mM treatment) to 6:1 (upon 10 mM treatment) and 4:1 (upon 30 mM treatment). Two double G:C----A:T transition mutants were characterized. In addition, this nitrosamine appears to be relatively more efficient at producing other kinds of mutations. In total 19 non-G:C----A:T mutations were identified. These included: A:T----G:C transitions, transversions and frameshifts. The relative contribution of these events was found also to decrease with increasing dose. These results may help explain why the parent carcinogen N-nitroso-N,N-dimethylamine is hepatotropic while other methylating carcinogens, similarly metabolized in the liver, are not.

Distribution and partitioning of trace metals in sediments of the lower reaches of the New Calabar River, Port Harcourt, Nigeria.

The distribution of trace metals in sediments of the lower reaches of the New Calabar River, Nigeria was evaluated together with the partitioning of their chemical species between five geochemical phases. Samplings were made in five zones at the lower reaches of the New Calaber River. All the trace metals were determined by AAS after selective chemical extractions and concentrations given in microg gm(-1) (dry weight basis). The average total concentrations found for trace metals in the sediment were ( mean +/- rsd.) Pb: 41.6 +/- 0.29, Zn: 31.60 +/- 0.42, Cd: 12.80 +/- 0.92, Co: 92 +/- 0.25, Cu: 25.5 +/- 0.65 and Ni: 3.2 +/- 0.25. Maxima and minima concentrations are inconsistent with previous studies in other rivers of this region. Spatial distribution revealed that the sources of trace metals into the river appeared to be of non-point. Five contamination indices were applied in studying the partitioning of the trace metals in the sediment. These indices provided bases for ascertaining the potential environmental risk of trace metals in the river system. The results denote high partition levels in the more mobile and more dangerous phases.

The dissimilar mutational consequences of SN1 and SN2 DNA alkylation pathways: clues from the mutational specificity of dimethylsulphate in the lacI gene of Escherichia coli.

The mutational specificity of the monofunctional alkylating agent dimethylsulphate has been determined through the DNA sequence characterization of 121 lacI-d mutations of Escherichia coli. The predominant mutation induced was the G:C----A:T transition (75%). Transversions constituted 20% of all mutation with the greatest contribution being that of G:C----T:A events (12%). Runs of G:C base pairs were the preferred sites of frameshift mutation. One 6-bp sequence (5'-CCCGCG-3') appeared to be highly susceptible to all classes of mutation and events within this sequence accounted for 33% of all mutations characterized. Although the distribution of G:C----A:T mutations appeared non-random, the site-specificity observed was quite different from that reported for SN1 alkylating agents. The results of this study highlight the differences between the consequences of SN1 and SN2 alkylation pathways.

Specificity of SOS mutagenesis in native M13lacI phage.

Base substitutions account for 90% of all forward mutations sequenced in unmodified M13lacI DNA grown in both UV-irradiated and nonirradiated hosts. The principal effect of SOS induction was an increase in the contribution of transversions, in particular A.T----T.A events.