Arrhythmogenic gene remodelling in elderly patients with type 2 diabetes with aortic stenosis and normal left ventricular ejection fraction.

NEW FINDINGS: What is the central question of this study? Type 2 diabetes is associated with a higher rate of ventricular arrhythmias compared with the non-diabetic population, but the associated myocardial gene expression changes are unknown; furthermore, it is also unknown whether any changes are attributable to chronic hyperglycaemia or are a consequence of structural changes. What is the main finding and its importance? We found downregulation of left ventricular ERG gene expression and increased NCX1 gene expression in humans with type 2 diabetes compared with control patients with comparable left ventricular hypertrophy and possible myocardial fibrosis. This was associated with QT interval prolongation. Diabetes and associated chronic hyperglycaemia may therefore promote ventricular arrhythmogenesis independently of structural changes. Type 2 diabetes is associated with a higher rate of ventricular arrhythmias, and this is hypothesized to be independent of coronary artery disease or hypertension. To investigate further, we compared changes in left ventricular myocardial gene expression in type 2 diabetes patients with patients in a control group with left ventricular hypertrophy. Nine control patients and seven patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal-averaged ECGs and echocardiograms before surgery. During surgery, a left ventricular biopsy was taken, and mRNA expressions for genes relevant to the cardiac action potential were estimated by RT-PCR. Mathematical modelling of the action potential and calcium transient was undertaken using the O'Hara-Rudy model using scaled changes in gene expression. Echocardiography revealed similar values for left ventricular size, filling pressures and ejection fraction between groups. No difference was seen in positive signal-averaged ECGs between groups, but the standard ECG demonstrated a prolonged QT interval in the diabetes group. Gene expression of KCNH2 and KCNJ3 were lower in the diabetes group, whereas KCNJ2, KCNJ5 and SLC8A1 expression were higher. Modelling suggested that these changes would lead to prolongation of the action potential duration with generation of early after-depolarizations secondary to a reduction in density of the rapid delayed rectifier K+ current and increased Na+ -Ca2+ exchange current. These data suggest that diabetes leads to pro-arrythmogenic changes in myocardial gene expression independently of left ventricular hypertrophy or fibrosis in an elderly population.

Effectiveness of out-patient based acute heart failure care: a pilot randomised controlled trial.

OBJECTIVES: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). METHODS: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. RESULTS: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient. CONCLUSIONS: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.

Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: a retrospective cohort study.

OBJECTIVE: To examine the relationship between hyperuricaemia, haemoconcentration and maternal and fetal outcomes in hypertensive pregnancies. DESIGN: Retrospective analysis of a database of hypertensive pregnancies. SETTING: St George Hospital, a major obstetric unit in Australia. POPULATION: A cohort of 1880 pregnant women without underlying hypertension or renal disease, referred for management of pre-eclampsia or gestational hypertension. METHODS: Demographic, clinical and biochemical data at time of referral and delivery were collected for each pregnancy. Women were grouped according to diagnosis (pre-eclampsia or gestational hypertension) and logistic regression analysis was used to determine the relationship between uric acid, haemoglobin, haematocrit and adverse outcomes; an α level of P < 0.01 was used for statistical significance. MAIN OUTCOME MEASURES: Composites of adverse maternal and fetal outcomes. RESULTS: In women with 'benign' GH (without proteinuria or any other maternal clinical feature of pre-eclampsia) gestation-corrected hyperuricaemia was associated with increased risk of a small-for-gestational-age infant (OR 2.5; 95% CI 1.3-4.8) and prematurity (OR 3.2; 95% CI 1.4-7.2), but not with adverse maternal outcome. In the whole cohort of hypertensive pregnant women (those with pre-eclampsia or gestational hypertension) the risk of adverse maternal outcome (OR 2.0; 95% CI 1.6-2.4) and adverse fetal outcome (OR 1.8; 95% CI 1.5-2.1) increased with increasing concentration of uric acid. Hyperuricaemia corrected for gestation provided additional strength to these associations. Haemoglobin and haematocrit were not associated with adverse pregnancy outcome. CONCLUSIONS: Hyperuricaemia in hypertensive pregnancy remains an important finding because it identifies women at increased risk of adverse maternal and particularly fetal outcome; the latter, even in women with gestational hypertension without any other feature of pre-eclampsia.

Anterior development in the parthenogenetic and viviparous form of the pea aphid, Acyrthosiphon pisum: hunchback and orthodenticle expression.

In the dipteran Drosophila, the genes bicoid and hunchback work synergistically to pattern the anterior blastoderm during embryogenesis. bicoid, however, appears to be an innovation of the higher Diptera. Hence, in some non-dipteran insects, anterior specification instead relies on a synergistic interaction between maternally transcribed hunchback and orthodenticle. Here we describe how orthologues of hunchback and orthodenticle are expressed during oogenesis and embryogenesis in the parthenogenetic and viviparous form of the pea aphid, Acyrthosiphon pisum. A. pisum hunchback (Aphb) mRNA is localized to the anterior pole in developing oocytes and early embryos prior to blastoderm formation - a pattern strongly reminiscent of bicoid localization in Drosophila. A. pisum orthodenticle (Apotd), on the other hand, is not expressed prior to gastrulation, suggesting that it is the asymmetric localization of Aphb, rather than synergy between Aphb and Apotd, that regulates anterior specification in asexual pea aphids.

Comprehensive survey of developmental genes in the pea aphid, Acyrthosiphon pisum: frequent lineage-specific duplications and losses of developmental genes.

Aphids exhibit unique attributes, such as polyphenisms and specialized cells to house endosymbionts, that make them an interesting system for studies at the interface of ecology, evolution and development. Here we present a comprehensive characterization of the developmental genes in the pea aphid, Acyrthosiphon pisum, and compare our results to other sequenced insects. We investigated genes involved in fundamental developmental processes such as establishment of the body plan and organogenesis, focusing on transcription factors and components of signalling pathways. We found that most developmental genes were well conserved in the pea aphid, although many lineage-specific gene duplications and gene losses have occurred in several gene families. In particular, genetic components of transforming growth factor beta (TGFbeta) Wnt, JAK/STAT (Janus kinase/signal transducer and activator of transcription) and EGF (Epidermal Growth Factor) pathways appear to have been significantly modified in the pea aphid.

The origin and evolution of segmentation.

Arthropods, annelids and chordates all possess segments. It remains unclear, however, whether the segments of these animals evolved independently or instead were derived from a common ancestor. Considering this question involves examining not only the similarities and differences in the process of segmentation between these phyla, but also how this process varies within phyla, where the homology of segments is generally accepted. This article reviews what is known about the segmentation process and considers various proposals to explain its evolution.

Role of angiotensin receptor blockers in the prevention and management of ischaemic stroke.

Angiotensin receptor blockers (ARB's) are an important class of antihypertensive agents and appear to have a role in the prevention and management of ischaemic stroke. We present a discussion of the data on ARB's in this important condition.

A comparison of antimicrobial susceptibility profile of urinary pathogens for the years, 1999 and 2003.

Urinary tract infection is a common condition worldwide; responsible for significant morbidity in both hospitalized and community patients. The laboratory records, for microbial isolates of infected urine and their susceptibility profiles for the years 1999 and 2003 were retrospectively reviewed and compared. In 2003, there was a significant decline in recovery ofCitrobacter spp compared to 1999. Conversely, the proportion of K pneumoniae, E coli and Enterococci increased dramatically in 2003, in both practices. For Proteus vulgaris and Proteus mirabilis, rates of isolation were increased in 2003, in hospital practice and community practice, respectively. Significant changes in antimicrobial susceptibility were also evident. A greater proportion of isolates from both practices were resistant to ampicillin, amoxicillin-clavulanic acid, cefuroxime, ceftazidime and cotrimoxazole in 2003 when compared to 1999. With respect to E coli, there were significant increases in prevalence of resistance to cefuroxime and amoxicillin-clavulanic acid. The overall resistance rate for norfloxacin remained relatively low and was unchanged for E coli. Continued surveillance of uropathogen resistance trends is important and this information should be communicated to clinicians. The feasibility of using the fluoroquinolones as a first line of therapy in urinary tract infection should be considered.

Molecular genetics of the renin-angiotensin system: implications for angiotensin II receptor blockade.

Angiotensin II (Ang II) is the main effector hormone of the renin-angiotensin system (RAS). The pathogenesis of many cardiovascular diseases, including heart failure and hypertension, appear to be related to Ang II production. The generation of Ang II involves angiotensin-converting enzyme (ACE) in circulating and tissue RAS's, as well as non-ACE pathways. ACE and other components of the RAS show natural mutations. In this review, we discuss the molecular genetics of the human RAS in relation to cardiovascular disease, including the clinical effects of known ACE molecular variants and possible pharmacological treatment strategies.

Cocaine and the heart.

Cocaine is the second commonest illicit drug used and the most frequent cause of drug related deaths. Its use is associated with both acute and chronic complications that may involve any system, the most common being the cardiovascular system. Cocaine misuse has a major effect in young adult drug users with resulting loss of productivity and undue morbidity with cocaine related cardiac and cerebrovascular effects. Many cocaine users have little or no idea of the risks associated with its use. Patients, health care professionals, and the public should be educated about the dangers and the considerable risks of cocaine use. This review concentrates on the cardiovascular effects of cocaine and their management.

Myocardial infarction in young adults.

Although myocardial infarction (MI) mainly occurs in patients older than 45, young men or women can suffer MI. Fortunately, its incidence is not common in patients younger than 45 years. However, the disease carries a significant morbidity, psychological effects, and financial constraints for the person and the family when it occurs at a young age. The causes of MI among patients aged less than 45 can be divided into four groups: (1) atheromatous coronary artery disease; (2) non-atheromatous coronary artery disease; (2) hyper-coagulable states; (4) MI related to substance misuse. There is a considerable overlap between all the groups. This article reviews the literature and highlights the practical issues involved in the management of young adults with MI.

Fecal bulk, energy intake, and serum cholesterol: regression response of serum cholesterol to apparent digestibility of dry matter and suboptimal energy intake in rats on fiber-fat diet.

Two experiments were conducted in the rat to determine the relationships of serum cholesterol (SC, mg/dl), apparent digestibility of dry matter (DDM, %), and digested energy intake (DE, kcal/day) at suboptimal level of energy. The energies in diet and feces were determined by calorimetry. DE as percentage of the National Research Council requirement (DE%) was suboptimal (70 to 85%). The experiments had four to five isofibrous diets, and no fiber diets, supplemented with 0.2% crystalline cholesterol (CChol). Animals in experiment 1 were fed varying amounts of feed with 18% coconut oil in the diets where as these in experiment 2 were given fixed amounts of feed with either 6 or 18% oil. The following regressions (p less than 0.001) for SC were found: experiment 1: -1157.7 -5.97 DDM +105.5 CCI -1.48 CCI2 (r2 0.35), where CCI = CChol, mg/day; -1888.4 -2.66 DE +120.97 CCI -1.62 CCI2 (r2 0.37). Experiment 2: 762.99 -6.15 DDM -0.8 fat cal % -0.87DE% (r2 0.31), where fat cal % = fat calories % of DE. Data indicate that at suboptimal energy intake, SC was inversely related to (1) DDM, (2) fat cal, and (3) total energy intake. Liver cholesterol lowering effect of the dietary fiber was also observed. The above findings help to elucidate various conflicting reports related to diet and blood cholesterol.

The prevalence and clinical significance of nocturnal hypertension in pregnancy.

OBJECTIVE: To determine (a) the prevalence of hypertension during sleep in pre-eclampsia and gestational hypertension, and (b) whether women with hypertension during sleep have worse pregnancy outcomes than hypertensive pregnant women with controlled (normal) blood pressure (BP) during sleep. DESIGN: Prospective double-blind cohort study. SETTING: Inpatients and outpatients managed in a day assessment unit (DAU) at St George Hospital, Sydney, Australia. PARTICIPANTS: A total of 186 hypertensive pregnant women, 158 of whom had successful 24 h BP monitoring; 40% had proteinuric pre-eclampsia (PE), 43% gestational hypertension (GH) and 17% essential hypertension (EH). INTERVENTIONS: Blood pressure, 24 h non-invasive, monitoring (Spacelabs 90207) was undertaken successfully in 158 women with PE, GH or EH, whether or not they were receiving antihypertensives. Women and clinicians were blinded to results of these BP monitors. Sleep hypertension was defined as BP > 117/68 mmHg at 26-30 weeks or > 123/72 mmHg after 30 weeks gestation. MAIN OUTCOME MEASURES: Maternal and fetal outcomes were compared between women with and without sleep hypertension and the prevalence of sleep hypertension was determined. RESULTS: Sleep hypertension was present in 59%, more commonly in PE (79%) than GH/EH (45%), P < 0.0001. Sleep hypertensives also had higher routine sphygmomanometer BPs [137(10)/91(7) mmHg; mean(SD)] than women with normal sleep BP [130(12)/ 87(8) mmHg] P = 0.007, and higher awake ambulatory blood pressure monitoring (ABPM) BPs [137(8)/88(7) versus 127(7)/79(6) mmHg], P < 0.0001. Awake, but not sleep, average heart rate was lower in sleep hypertensives [85(11) versus 91 (10) beats per minute, bpm], P = 0.002. Sleep hypertensives had a significantly greater frequency of renal insufficiency, liver dysfunction, thrombocytopenia and episodes of (awake) severe hypertension (P < 0.05), as well as lower birth weight babies [2715 (808) versus 3224(598) g, P < 0.0001]. CONCLUSIONS: Hypertension during sleep is a common finding in women with hypertensive disorders of pregnancy, particularly pre-eclampsia. These women also have higher awake BPs and a greater frequency of adverse maternal and fetal outcomes. These findings are largely explained by the greater likelihood of pre-eclamptics having sleep hypertension.

Angiotensin converting enzyme (ACE) gene expression in the human left ventricle: effect of ACE gene insertion/deletion polymorphism and left ventricular function.

AIMS: We investigated the effect of the angiotensin converting enzyme (ACE) I/D polymorphism and left ventricular (LV) function on ACE gene expression in tru-cut LV myocardial biopsies from 50 consecutive patients (II: 18, ID: 18, DD: 14; 40 males) with ischaemic heart disease undergoing coronary artery bypass grafting (CABG). METHODS: The polymerase chain reaction was used for ACE genotyping. LV function [normal (n=22) or impaired] was determined by left ventriculography at cardiac catheterisation prior to bypass surgery. ACE expression was determined (n=46) by a competitive quantitative reverse transcription PCR assay using 5x10(5), 12. 5x10(5) and 20x10(5) copies of a mutant DNA internal standard (IS). PCR products were analysed by negative film photography and laser densitometry to determine the number of ACE transcripts present. RESULTS: Mean age was similar (II: 59.1+/-10.4, ID: 57.0+/-10.6, DD: 61.4+/-6.2; P=NS) with no differences between groups in sex (P=0. 25); hypertension, P=0.31; previous myocardial infarction, P=0.44; LV function, P=0.23; and ACE inhibitor therapy, P=0.06. ACE expression per 100 ng of total RNA varied with genotype [<5x10(5) copies in II: 6, 5-12.5x10(5) copies in II: 6, ID: 16, DD: 4; and >12.5x10(5) (II: 4, ID: 2, DD: 8), Kendall's tau-b coefficient (tau(b))=0.43, P=0.003]. Impaired LV function also correlated with higher levels of ACE expression, Kendall's tau(b)=0.40, P=0.001. CONCLUSION: ACE gene expression in the left ventricle varied with ACE genotype and LV function in IHD patients undergoing CABG.

Myocardial perforation associated with the use of the Gensini ventriculography catheter.

We describe myocardial perforation during left ventriculography using the Gensini catheter in two patients with aortic valve disease. In each case this occurred despite careful catheter positioning and prior 'test' injection of contrast agent. The use of the Gensini catheter for left ventriculography in this circumstance is seriously questioned.

Coronary arteriographic and pathological findings in a case of primary leiomyosarcoma of the heart.

A case of primary leiomyosarcoma of the heart diagnosed during life is described. Selective coronary arteriography and transoesophageal echocardiography (TOE) aided pre-operative differentiation from the more common atrial myxoma.

What do women feel about community-based antenatal care?

OBJECTIVE: This study evaluated women's perceptions of a new community-based model of continuity of antenatal care, the St George Outreach Maternity Project (STOMP). The model was established in an attempt to address some of the ongoing concerns and criticisms regarding antenatal care in Australia: lack of continuity of care and caregiver; prolonged waiting times; and inaccessible clinics. METHODS: A randomised controlled trial was conducted with 1,089 women (550 in the experimental group and 539 in the control group). The experimental group (the STOMP group) received antenatal care from small teams of midwives and an obstetrician in community-based settings. Data were collected using a questionnaire administered at 36 weeks' gestation, with a response rate of 75%. RESULTS: Women in the STOMP group reported waiting significantly less time for antenatal visits with easier access to care. STOMP group women also reported a higher perceived 'quality' of antenatal care compared with the control group. STOMP group women saw slightly more midwives and fewer doctors than control group women did. CONCLUSION AND IMPLICATIONS: This model of care has implications for the planning and provision of antenatal services within the Australian public health system, which is increasingly moving towards a community-based emphasis. Antenatal care is a service that can be successfully transferred into community-based settings with benefits for women.

Management of acute myocardial infarction in the public sector in the Bahamas.

In 1996 and 1997, 52 patients were admitted to the Princess Margaret Hospital, Nassau, Bahamas, with a confirmed diagnosis of acute myocardial infarction (AMI). The average time to presentation after the onset of symptoms was 18 hours, with 56% of patients presenting within 12 hours. Risk factors identified for ischaemic heart disease were hypertension (77%), obesity (62%), diabetes mellitus (35%), tobacco smoking (25%), a family history of coronary artery disease (17%) and hypercholesterolaemia (8%). Medications administered in the treatment of AMI included oral nitrates (96%), intravenous heparin (90%), beta-blockers (65%), morphine (15%), thrombolytic agents (8%) and lignocaine (4%). In hospital post myocardial infarction complications were angina (23%), arrhythmias (12%) and cardiac failure (10%). The average hospital stay was eight days, with a mortality rate of 19%. These results show that there is considerable room for improvement, particularly in the use of thrombolytic therapy, to ensure that all patients receive optimal acute and post myocardial infarction care.

Community-based continuity of midwifery care versus standard hospital care: a cost analysis.

This paper reports the costs of providing a new model of maternity care compared to standard care in an Australian public hospital. The mean cost of providing care per woman was lower in the group who had the new model of care compared with standard care ($2,579 versus $3,483). Cost savings associated with new model of care were maintained even after costs associated with admission to special care nursery were excluded. The cost saving was also sustained even when the caesarean section rate in the new model of care increased to beyond that of the standard care group.