The adaptation and translation of the PEACH™ RCT intervention: the process and outcomes of the PEACH™ in the community trial.

OBJECTIVE: To describe the process and report selected outcomes of translating an effective child weight management initiative (PEACH™) from a randomised controlled trial intervention to a community health programme. STUDY DESIGN AND METHODS: Pre-post study design utilising the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) evaluation framework. Adaptation of PEACH™ required significant promotional activity and consideration of legal, ethical and financial issues. PEACH™ components were revised and an evaluation design based on the RE-AIM framework was developed. Facilitator training workshops were made available to South Australian health or education professionals initially, then opened up to new graduates, interstate dietitians and others interested in professional development. Facilitators completed pretraining and post-training questionnaires and a third questionnaire following programme delivery. Data were collected from families by facilitators and returned to university staff for assessment of change (baseline to programme end) in body mass index (BMI) and waist circumference (WC) z-scores. RESULTS: Changes to organisational and political environments prevented maximum programme reach and adoption. Nonetheless, data indicated that PEACH™ was effective at improving facilitators' confidence (P < 0.05) and children's (n = 37) BMI z-score (-0.17, 95% confidence interval [CI]: 0.03:0.30, P = 0.016), WC z-score (-0.14, 95% CI: -0.02:0.30, P = 0.09) and lifestyle behaviours. Collection of maintenance data was prevented due to time and financial constraints. CONCLUSIONS: Translational research needs to develop ways to effectively and efficiently bridge the gap between behavioural research and practice to improve the adoption of evidence-based approaches to child weight management. Nutrition educators and researchers can drive these nutrition-focussed translational research efforts forward. Funding bodies and health service organisations are encouraged to provide financial and structural support for such activity.

Dietary intake in Australian children aged 4-24 months: consumption of meat and meat alternatives.

Meat/meat alternatives (M/MA) are key sources of Fe, Zn and protein, but intake tends to be low in young children. Australian recommendations state that Fe-rich foods, including M/MA, should be the first complementary foods offered to infants. The present paper reports M/MA consumption of Australian infants and toddlers, compares intake with guidelines, and suggests strategies to enhance adherence to those guidelines. Mother-infant dyads recruited as part of the NOURISH and South Australian Infants Dietary Intake studies provided 3 d of intake data at three time points: Time 1 (T1) (n 482, mean age 5·5 (SD 1·1) months), Time 2 (T2) (n 600, mean age 14·0 (SD 1·2) months) and Time 3 (T3) (n 533, mean age 24 (SD 0·7) months). Of 170 infants consuming solids and aged greater than 6 months at T1, 50 (29%) consumed beef, lamb, veal (BLV) or pork on at least one of 3 d. Commercial infant foods containing BLV or poultry were the most common form of M/MA consumed at T1, whilst by T2 BLV mixed dishes (including pasta bolognaise) became more popular and remained so at T3. The processed M/MA increased in popularity over time, led by pork (including ham). The present study shows that M/MA are not being eaten by Australian infants or toddlers regularly enough; or in adequate quantities to meet recommendations; and that the form in which these foods are eaten can lead to smaller M/MA serve sizes and greater Na intake. Parents should be encouraged to offer M/MA in a recognisable form, as one of the first complementary foods, in order to increase acceptance at a later age.

A GIP/xenin hybrid in combination with exendin-4 improves metabolic status in db/db diabetic mice and promotes enduring antidiabetic benefits in high fat fed mice.

The current study has determined the ability of exendin-4 to augment the antidiabetic benefits of the recently characterised GIP/xenin hybrid, (DAla2)GIP/xenin-8-Gln. As such, combined activation of metabolic pathways linked to various gut derived hormones has been shown to exert complementary beneficial metabolic effects in diabetes. (DAla2)GIP/xenin-8-Gln and exendin-4 were administered twice daily to high fat fed (HFF) or db/db mice for 28 days and antidiabetic benefits assessed. Persistence of beneficial metabolic effects in HFF mice was also examined. Twice-daily injection of (DAla2)GIP/xenin-8-Gln for 28 days in HFF mice significantly reduced energy intake, body weight, circulating glucose, HbA1c and improved glucose tolerance and insulin sensitivity. Overall pancreatic islet, alpha- and beta-cell areas were reduced, with concurrent reduction in alpha- and beta-cell proliferation that was more apparent in the combined treatment group. Addition of exendin-4 to (DAla2)GIP/xenin-8-Gln therapy did not significantly improve metabolic control. Remarkably, beneficial effects were still evident 14 days following complete cessation of peptide administration. Thus, circulating glucose and insulin, HbA1c concentrations and glucose tolerance were still significantly improved when compared to control HFF mice on day 42, with minimal changes to pancreatic islet architecture. In contrast to HFF mice, combined treatment of db/db mice with (DAla2)GIP/xenin-8-Gln plus exendin-4 was required to induce beneficial effects on key metabolic parameters, which were not observed with either treatment alone. This included improvements in glucose tolerance and insulin sensitivity, but no effect on pancreatic architecture. These studies highlight the clear, and persistent, metabolic advantages of sustained activation of GLP-1 receptors, alongside concurrent activation of related GIP and xenin cell signalling pathways, in diabetes.

The impact of diabetes mellitus on two-year mortality following contemporary percutaneous coronary intervention: implications for revascularization practice.

OBJECTIVE: To assess the impact of diabetes on 2-year mortality in current PCI practice. BACKGROUND: In patients with coronary artery disease undergoing revascularization, diabetes mellitus is associated with higher mortality. METHODS: A retrospective analysis was done of all patients undergoing PCI at our tertiary center between January 2000 and December 2004. There were 6,160 PCI procedures performed in 5,759 patients who received at least one stent. Of these patients, 801 (13.9%) were diabetic and 4,958 (86.1%) were nondiabetic. The primary outcome measure of the study was all-cause mortality. All patients were followed up for a period of 2 years. Multivariate logistic regression analysis was used to test for a potential independent association between diabetic status and follow-up mortality. RESULTS: Before adjustment, a trend toward higher mortality was observed in diabetic patients compared to non-diabetics at 1 year (3.2% vs 2.4%) and 2 years (5.1% vs 3.8%), P = 0.12. Independent predictors for mortality were increasing age, renal dysfunction, peripheral vascular disease, NYHA class >2, urgent PCI, treating left main stem lesions, vessel diameter < or = 2.5 mm, and 3-vessel disease. The use of drug-eluting stent was associated with a reduction in mortality. Diabetes was found to have no independent impact on mortality following PCI (odds ratio = 1.08; 95% confidence intervals = 0.73-1.60; P = 0.71). CONCLUSION: The presence of diabetes was not an independent predictor of mortality following PCI. A diabetic patient that does not require insulin treatment and has no evidence of macro- or microvascular diabetic disease could enjoy a PCI outcome similar to nondiabetic subjects.

Characterisation of Glucose-Dependent Insulinotropic Polypeptide Receptor Antagonists in Rodent Pancreatic Beta Cells and Mice.

Hypersecretion and alterations in the biological activity of the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), have been postulated as contributing factors in the development of obesity-related diabetes. However, recent studies also point to weight-reducing effects of GIP receptor activation. Therefore, generating precise experimental tools, such as specific and effective GIP receptor (GIPR) antagonists, is of key significance to better understand GIP physiology. Thus, the primary aim of the current study was to uncover improved GIPR antagonists for use in rodent studies, using human and mouse GIP sequences with N- and C-terminal deletions. Initial in vitro studies revealed that the GIPR agonists, human (h) GIP(1-42), hGIP(1-30) and mouse (m) GIP(1-30), stimulated (P < 0.01 to P < 0.001) insulin secretion from rat BRIN-BD11 cells. Analysis of insulin secretory effects of the N- and C-terminally cleaved GIP peptides, including hGIP(3-30), mGIP(3-30), h(Pro3)GIP(3-30), hGIP(5-30), hGIP(3-42) and hGIP(5-42), revealed that these peptides did not modulate insulin secretion. More pertinently, only hGIP(3-30), mGIP(3-30) and h(Pro3)GIP(3-30) were able to significantly (P < 0.01 to P < 0.001) inhibit hGIP(1-42)-stimulated insulin secretion. The human-derived GIPR agonist sequences, hGIP(1-42) and hGIP(1-30), reduced (P < 0.05) glucose levels in mice following conjoint injection with glucose, but mGIP(1-30) was ineffective. None of the N- and C-terminally cleaved GIP peptides affected glucose homeostasis when injected alone with glucose. However, hGIP(5-30) and mGIP(3-30) significantly (P < 0.05 to P < 0.01) impaired the glucose-lowering action of hGIP(1-42). Further evaluation of these most effective sequences demonstrated that mGIP(3-30), but not hGIP(5-30), effectively prevented GIP-induced elevations of plasma insulin concentrations. These data highlight, for the first time, that mGIP(3-30) represents an effective molecule to inhibit GIPR activity in mice.

Impact of a 6-month family-based weight management programme on child food and activity behaviours: short-term and long-term outcomes of the PEACH™ intervention.

BACKGROUND: The PEACH™ randomized controlled trial measured changes to children's food and activity behaviours following participation in a weight management programme. We have previously reported a 10% reduction in body mass index z-score at intervention end (6-month post-baseline) that was maintained to 24 months with no further intervention for the full study sample. OBJECTIVES: The objective of the study is to report changes in food and activity outcomes in the full sample at (i) the end of the 6-month intervention and (ii) 24-month post-baseline (18-month post-intervention). METHODS: Changes in dietary and activity outcomes were assessed over time (baseline: n = 169, 8.1 ± 1.2 years, body mass index z-score 2.72 ± 0.62). Dietary intake was assessed using the Child Dietary Questionnaire, and times spent active and sedentary were assessed using a study-specific questionnaire. Linear mixed models were used. RESULTS: There were significant time effects for all Child Dietary Questionnaire scores and activity and sedentary behaviours in the expected direction. Significant sex effects were observed for fruit and vegetable and sweetened beverages scores and for time spent in small screen-based activity. CONCLUSIONS: This is one of few child weight management studies to report short-term and long-term behaviour outcomes. It demonstrates that an intervention promoting food and activity behaviours consistent with guidelines can achieve modest changes, mediating improvements in relative weight.

PGC-1α4 gene expression is suppressed by the IL-6-MEK-ERK 1/2 MAPK signalling axis and altered by resistance exercise, obesity and muscle injury.

AIM: PGC-1α4 is a novel regulator of muscle hypertrophy; however, there is limited understanding of the regulation of its expression and role in many (patho)physiological conditions. Therefore, our purpose was to elicit signalling mechanisms regulating gene expression of Pgc1α4 and examine its response to (patho)physiological stimuli associated with altered muscle mass. METHODS: IL-6 knockout mice and pharmacological experiments in C2C12 myocytes were used to identify regulation of Pgc1α4 transcription. To examine Pgc1α4 gene expression in (patho)physiological conditions, obese and lean Zucker rats with/without resistance exercise (RE), ageing mice and muscle regeneration from injury were examined. RESULTS: In IL-6 knockout mice, Pgc1α4mRNA was ~sevenfold greater than wild type. In C2C12 cells, Pgc1α4mRNA was suppressed ~70% by IL-6. Suppression of Pgc1α4 by IL-6 was prevented by MEK-ERK-MAPK inhibition. RE led to ~260% greater Pgc1α4mRNA content in lean rats. However, obese Zucker rats exhibited ~270% greater Pgc1α4mRNA than lean, sedentary with no further augmentation by RE. No difference was seen in IL-6mRNA or ERK-MAPK phosphorylation in Zucker rats. Aged mice demonstrated ~50% lower Pgc1α4mRNA and ~fivefold greater ERK-MAPK phosphorylation than young despite unchanged Il-6mRNA. During muscle regeneration, Pgc1α4 content is ~30% and IL-6mRNA >threefold of uninjured controls 3 days following injury; at 5 days, Pgc1α4 was >twofold greater in injured mice with no difference in IL-6mRNA. CONCLUSION: Our findings reveal a novel mechanism suppressing Pgc1α4 gene expression via IL-6-ERK-MAPK and suggest this signalling axis may inhibit Pgc1α4 in some, but not all, (patho)physiological conditions.

Translational machinery of mitochondrial mRNA is promoted by physical activity in Western diet-induced obese mice.

AIM: Mitochondria-encoded proteins are necessary for oxidative phosphorylation; however, no report has examined how physical activity (PA) and obesity affect mitochondrial mRNA translation machinery. Our purpose was to determine whether Western diet (WD)-induced obesity and voluntary wheel running (VWR) impact mitochondrial mRNA translation machinery and whether expression of this machinery is dictated by oxidative phenotype. METHODS: Obesity was induced with 8-wk WD feeding, and in the final 4 wks, half of mice were allowed VWR. Mitochondrial mRNA translation machinery including initiation factors (mtIF2/3), elongation factor Tu (TUFM) and translational activator (TACO1), and mitochondria-encoded proteins (CytB and ND4) was assessed by immunoblotting. The relation of mitochondrial mRNA translation to muscle oxidative phenotype was assessed using PGC-1α transgenic overexpression (MCK-PGC-1α vs. wild-type mice) and comparing across muscle groups in wild-type mice. RESULTS: mtIF3 and TACO1 proteins were ~45% greater in VWR than sedentary (SED), and TACO1 and mtIF2 proteins were ~60% and 125% greater in WD than normal chow (NC). TUFM protein was ~50% lower in WD-SED than NC-SED, but ~50% greater in WD-VWR compared to NC-SED. CytB and ND4 were ~40% greater in VWR and ND4 was twofold greater with WD. TUFM, TACO1, ND4 and CytB were greater in MCK-PGC-1α compared to wild-type, and mtIF2/3 contents were not different. In oxidative muscle (soleus), mitochondrial translation machinery was elevated compared to mixed (gastrocnemius) or glycolytic (extensor digitorum longus) muscles. CONCLUSION: These data suggest a novel mechanism promoting mitochondrial function by translation of mitochondrial protein following PA. This may act to promote muscle health by PA in obesity.

On the reactivities of the tryptophan residues of human alpha-lactalbumin to 2-hydroxy-5-nitrobenzyl bromide.

The reaction of human alpha-lactalbumin with the tryptophan reagent 2-hydroxy-5-nitrobenzyl bromide has been studied. This protein has 3 tryptophan residues (Trp-60, Trp-104 and Trp-118) all of which are accessible to the reagent at pH 2.7 or 7. Trp-60 of human alpha-lactalbumin is much more reactive than Trp-60 of bovine alpha-lactalbumin (Barman, T. E. (1972) Biochim. Biophys. Acta 257, 297-313). As with bovine alpha-lactalbumin, at pH 2.7, 2-hydroxy-5-nitrobenzyl bromide is specific for tryptophan but at pH 7 His-32 also reacts. When treated with the tryptophan reagent, both alpha-lactalbumins lose their specifier protein activities in the lactose synthase (UDPgalactose:D-glucose 4-beta-galactosyltransferase, EC 2.4.1.22) reaction.

Diet-induced obesity alters anabolic signalling in mice at the onset of skeletal muscle regeneration.

AIM: Obesity is classified as a metabolic disorder that is associated with delayed muscle regeneration following damage. For optimal skeletal muscle regeneration, inflammation along with extracellular matrix remodelling and muscle growth must be tightly regulated. Moreover, the regenerative process is dependent on the activation of myogenic regulatory factors (MRFs) for myoblast proliferation and differentiation. The purpose of this study was to determine how obesity alters inflammatory and protein synthetic signalling and MRF expression at the onset of muscle regeneration in mice. METHODS: Forty-eight male C57BL/6J mice (3 weeks old) were randomly assigned to either a high-fat diet (HFD, 60% fat) or a lean diet (10% fat) for 12 weeks. At 15 weeks, bupivacaine was injected into the tibialis anterior (TA) of the injured group (n = 5-8/group) and PBS was injected into the control (n = 5-6). The TA was excised 3 or 28 days after injection. RESULTS: We demonstrated impaired muscle regeneration in obese mice. The obese mice had reduced IL-6, MyoD and IGF-1 mRNA abundance compared to the lean mice (P < 0.05). Three days following muscle damage, TNF-α mRNA and protein levels of P-STAT3 and P-Akt were 14-fold, fourfold and fivefold greater in the lean mice respectively. However, there were no differences observed in the obese injured group compared to the uninjured group. Moreover, p70S6K1 was threefold greater in lean injured mice compared to uninjured but was reduced by 28% in the obese injured mice. CONCLUSION: Obese mice have impaired inflammatory and protein synthetic signalling that may negatively influence muscle regeneration.

The development of corticotrophs in the fetal sheep pars distalis: the effect of adrenalectomy or cortisol infusion.

At 90 days gestation a uniquely fetal-type and an adult-type corticotroph have been observed in the fetal sheep pars distalis (term approximately 147 days). Between 90 and 130 days gestation the fetal type is predominant, and its numbers decline toward term. In this study the effect of the endogenous cortisol surge on the change in the population of corticotrophs in the pars distalis was investigated in sheep fetuses after bilateral adrenalectomy at 120 days gestation or after an infusion of 2 mg cortisol/day between 109 and 115 days gestation. The total proportion of corticotrophs, expressed as a percentage, decreased significantly (P less than 0.01) from 115 days in saline-infused controls (21.09 +/- 1.10%) and 135 days in intact controls (14.59 +/- 1.12%). The percentage of adult-type corticotrophs increased significantly (P less than 0.01) from 5.65 +/- 0.77 at 115 days, to 11.93 +/- 1.41 at 135 days. The percentage of fetal-type corticotrophs decreased significantly (P less than 0.001) from 14.91 +/- 0.35 at 115 days to 2.33 +/- 0.48 at 135 days. A small proportion of ACTH-immunoreactive cells could not be defined as either adult- or fetal-type corticotrophs. These changes in the corticotroph population had not occurred at 135 days in fetuses that had been adrenalectomized at 120 days; the percentage of corticotrophs relative to unstained cells (21.70 +/- 0.46%), the percentage of adult-type corticotrophs (6.42 +/- 0.29%), and the percentage of fetal-type corticotrophs (14.65 +/- 0.49%) were similar to those in 115-day-old fetuses, indicating that the normal change in the corticotroph population between 115 and 135 days gestation was dependent upon the presence of the fetal adrenal. In fetuses exposed to exogenous cortisol between 109 and 115 days gestation, the percentage of corticotrophs relative to unstained cells (16.53 +/- 1.68%), the percentage of adult-type corticotrophs (12.40 +/- 1.34%), and the percentage of fetal-type corticotrophs (3.78 +/- 0.58%) were similar to those at 135 days. This indicates that a short period of increased fetal plasma cortisol can bring about premature maturation of the corticotrophs in the fetal sheep pars distalis. We have also described an ACTH-immunoreactive cell which has characteristics of both an adult- and a fetal-type corticotroph. Its morphological appearance suggests that it may be a transitional stage from the fetal- to the adult-type corticotroph.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of adrenalectomy or long term cortisol or adrenocorticotropin (ACTH)-releasing factor infusion on the concentration and molecular weight distribution of ACTH in fetal sheep plasma.

It is unclear whether the maturation of corticotrophs from the fetal to the adult type in the fetal sheep pituitary in late gestation is associated with changes in the sensitivity of the fetal pituitary to corticotrophic secretagogues and in the form of ACTH-containing peptides (IR-ACTH) secreted into the circulation. The maturation of the pituitary corticotroph population is known to be accelerated by intrafetal cortisol infusion and delayed by bilateral fetal adrenalectomy. We have therefore investigated the mol wt profile of IR-ACTH present in fetal sheep plasma from 110 days gestation until term (147 +/- 3 days) and determined whether intrafetal cortisol infusion between 105-117 days (2.5 mg cortisol/day), or bilateral fetal adrenalectomy can alter the mol wt profile of IR-ACTH in fetal sheep plasma. We have also investigated whether prior exposure to cortisol alters the subsequent responsiveness of the fetal pituitary to a long term infusion of ovine (o) CRF (10 micrograms oCRF/day). In the control group, the proportion of IR-ACTH which eluted in the low-mol wt (LMW) range (i.e. less than 12K) was significantly higher between 121-125 days (43.9 +/- 4.2%) than between 126-139 days (26.8 +/- 9.3%) but not different to that after 140 days gestation (29.9 +/- 5.5%). Between 110-117 days, cortisol infusion had no effect on the proportion of IR-ACTH in the LMW range (43.9 +/- 5.7%, saline infused; 44.1 +/- 2.4%, cortisol infused). Between 121-125 days, the proportion of IR-ACTH in the LMW range in the CRF-infused groups (with or without prior exposure to cortisol) was significantly lower (27.4 +/- 2.1%) than in the saline-infused control group. In contrast, after fetal adrenalectomy, the proportion of IR-ACTH in the LMW range between 126-139 days was significantly higher (48.0 +/- 6.7%) than in intact control animals (23.8 +/- 3.5%). We conclude that the change in the mol wt profile of IR-ACTH in fetal plasma after 125 days may be a consequence of changes in the morphological and/or functional characteristics of the corticotrophic cells in the fetal pituitary. Infusion of oCRF appears to accelerate the normal maturation of the fetal pituitary-adrenal relationship, and oCRF acting either directly or via secretion of cortisol may play a role in the posttranslational processing of POMC in the fetal sheep pituitary after 125 days gestation.

Differential free-radical activity after successful and unsuccessful thrombolytic reperfusion in acute myocardial infarction.

BACKGROUND: Free-radical generation after successful thrombolysis in acute myocardial infarction may jeopardize ischaemic but viable myocardium, thus limiting the optimal benefits of reperfusion. METHODS: Circulating free-radical activity was assessed in 25 consecutive patients with acute myocardial infarction. Those who successfully reperfused (Group A) were compared with those who did not (Group B). We also compared patients who had or had not developed Q waves and patients with and without previous angina or myocardial infarction. All patients presented within 6 h of the onset of chest pain and received standard intravenous streptokinase therapy. Free-radical activity in serial serum samples collected over 72 h was measured using the percentage molar ratio (PMR) of the concentrations of 9,11-linoleic acid to 9,12-linoleic acid, and malonaldehyde concentration. RESULTS: Throughout the study period Group A (n = 11) showed significantly greater change in serum PMR and malonaldehyde levels compared with Group B (n = 14) (P < 0.01). PMR differences between the two groups were most pronounced at 3 and 12 h (P < 0.001). Patients with non-Q-wave myocardial infarction (n = 5) showed significantly greater changes in serum PMR and malonaldehyde levels (P < 0.01) compared with those with Q-wave infarction (n = 20). A history of previous infarction or angina had no apparent effects on the changes in serum free-radical activity. CONCLUSIONS: Successful early reperfusion and non-Q-wave myocardial infarction are both associated with a significantly greater increase in the levels of markers of serum free-radical activity immediately after infarction. The results support present concepts of free-radical-mediated reperfusion injury. Use of these assays may identify those patients who may be at risk from free-radical-mediated reperfusion injury.

Total coronary arterial occlusion: real or apparent?

We describe a case in which the angiographic appearance of total occlusion of the left anterior descending coronary artery was not due to a complete anatomical obstruction, but due to competitive and retrograde flow in the distal segment of the artery from collaterals via the contralateral vessel. This case has implications on our current practice and results of coronary angioplasty in total coronary arterial occlusion.

Effect of completeness of revascularization on clinical outcome in patients with multivessel disease presenting with unstable angina who undergo percutaneous coronary intervention.

We evaluated the current short- and medium-term outcomes of complete revascularization, compared to culprit lesion percutaneous coronary intervention (PCI), in patients with multivessel coronary disease presenting with unstable angina. One hundred fifty-one patients with multivessel coronary disease presented to a tertiary cardiothoracic center with unstable angina/non-ST elevation myocardial infarction (UA/NSTEMI) between January 2000 and September 2001. In group A (n=71), the intended strategy was complete revascularization by multivessel PCI. In group B (n=80), culprit lesion PCI was intended despite the presence of other lesions amenable to PCI (B1) or due to confounding anatomical factors (B2). Clinical variables and endpoints were collected from patient notes, a dedicated database and telephone follow-up, and included recurrent stable and unstable angina, need for repeat PCI or elective coronary artery bypass graft, incidence of non-fatal myocardial infarction (MI) and death. Baseline characteristics were similar in each group. Procedural success was achieved in over 95% of cases in both groups with high stent implantation rates (>96%). There was no observed difference in mortality or incidence of MI between the groups. Compared to group A, more patients in group B1 had residual angina [22.8% (13/57) versus 9.9% (7/71); p=0.041] and required further PCI [17.5% (10/57) versus 7.0% (5/71); p=0.045]. There was a non-significant trend toward fewer readmissions for UA and less long-term antianginal medication in group A [38.0% (27/71) versus 52.6% (30/57); p=0.043]. Complete and culprit lesion revascularization by PCI are safe methods of treating patients with multivessel coronary disease presenting with UA/NSTEMI. Reductions in residual angina, repeat PCI and need for antianginal therapies suggest that complete revascularization should be the strategy of choice when possible.

Distribution of trimipramine and its major metabolites in a fatal overdose case.

A fatality following ingestion of the tricyclic antidepressant trimipramine (Surmontil) is described. Quantitation was performed by high-performance liquid chromatography. Trimipramine and desmethyltrimipramine concentrations were 4.8 and 2.1 mg/L, respectively, in postmortem blood. The concentration of trimipramine, desmethyltrimipramine, and their respective 2-hydroxy metabolites were also measured in liver and urine. Analysis of gastric contents revealed a tricyclic antidepressant drug. These findings are compared to previously published reports of trimipramine-related fatalities.

Toxicologic studies in a fatal overdose of 2,4-D, mecoprop, and dicamba.

A suicidal poisoning committed by a 61-year-old woman, who ingested an unknown quantity of Killex, containing in aqueous solution 100 g/L of (2,4-dichlorophenox)acetic acid (2,4-D), 50 g/L of mecoprop, and 9 g/L of dicamba as amine salts is described. Quantitation of chlorophenoxy acids was performed by extraction from an acidified mixture and concentration before high performance liquid chromatography analysis. All three herbicides were separated in a phosphate buffer/acetonitrile mixture at 280 nm on a RP-8 column. Concentrations of herbicides found were: in blood--520-mg/L 2,4-D, 530-mg/L mecoprop, and 170-mg/L dicamba; in urine--670-mg/L 2,4-D and 520-mg/L mecoprop; in bile--340-mg/L 2,4-D, 530-mg/L mecoprop, and 140-mg/L dicamba; and in liver--540-mg/Kg 2,4-D, 500-mg/Kg mecoprop, and less than 100-mg/Kg dicamba. Liquid chromatography was found to be a reliable method for herbicide quantitation in biological tissues and fluids. The technique offered definite advantages over ultraviolet spectrophotometry and avoids the derivatization requirement for gas chromatography.

Disorders of the avian integument.

The avian integument consists of highly specialized structures that show extreme variations between species. Feathers are the most obvious part of the integument, and their color and beauty forms an important basis for the attraction of birds to humans. Any disorder in the feathers can be distressing for a client and frustrating for the avian practitioner. The cause of some disorders may be apparent, but others have a complex pathogenesis involving management, human-bird interaction, malnutrition, psychologic factors, disease, or hormone imbalances.

The pathology of psittacine beak and feather disease.

Psittacine beak and feather disease is characterised by loss of feathers, abnormally shaped feathers and overgrowth and irregularity of the surface of the beak. The disease occurs in a number of psittacine species including the Sulphur-crested Cockatoo, Lovebirds , Budgerigars and Galahs . The abnormal appearance of feathers and beak is due to a dystrophic process within the epidermis of the feather and beak. The process consists of epidermal cell necrosis, epidermal hyperplasia and hyperkeratosis. Many of the feather abnormalities are due to retention of a hyperkeratotic feather sheath. A characteristic microscopic finding is the presence of macrophages containing purple intracytoplasmic inclusions in affected epidermis and feather pulp. The inclusions consist of aggregates of particles 17 to 22 nm in diameter. Similar but smaller inclusions occur in epidermal cells. In addition, non-suppurative inflammation occurs in the feather pulp. The findings are suggestive of a viral infection.

Transmitral Doppler assessment of left ventricular diastolic function during coronary artery bypass surgery.

OBJECTIVE: To evaluate which Doppler transmitral velocity indices of left ventricular diastolic function change with alteration of left ventricular filling pressure. METHODS: Twenty-two patients undergoing coronary artery bypass surgery. The effect of fluid loading on indices derived from the transmitral Doppler waveform, recorded by a trans-oesophageal echocardiography, was evaluated using a generalised linear statistical model. RESULTS: E-wave maximum velocity, E-wave acceleration time and slope, E-wave deceleration slope, A-wave maximum velocity and E/A wave maximum velocity ratio showed significant changes after alterations in left ventricular filling pressure. E-wave deceleration time and E-wave maximum velocity/time velocity integral showed no significant change after fluid loading. CONCLUSION: Several commonly used Doppler derived indices of left ventricular diastolic function are significantly affected by changes in filling pressure of the left ventricle. This may limit the usefulness of the Doppler method for serial assessment of diastolic function when the left ventricular filling pressure has changed between assessments. Only the E-wave deceleration time did not show significant changes and might be a useful Doppler index for the serial measurement of left ventricular compliance but this needs to be confirmed with haemodynamic measurements.