Utilisation of outpatient cardiac rehabilitation in Queensland

OBJECTIVES: To determine patient participation rates in outpatient cardiac rehabilitation (OCR) programs; ascertain the barriers to participation; and evaluate the quality of OCR programs. DESIGN AND SETTING: Retrospective cohort study of patient separations from selected public and private Queensland hospitals; questionnaire survey of hospitals and all registered OCR programs. PARTICIPANTS: Patients discharged with cardiac diagnoses between 1 July 1999 and 30 June 2000 from 31 hospitals (24 public; 7 private). MAIN OUTCOME MEASURES: Rates of referral of hospitalised patients to OCR programs; rates of program attendance and completion; barriers to OCR referral and attendance. RESULTS: 15 186 patients were discharged with cardiac diagnoses from participating hospitals, of whom 4346 (29%) were referred to an OCR program after discharge, compared with an estimated 59% (8895/15 186) of patients who were eligible for such a program. Proportionately more patients were referred from secondary (38% [1720/4500]) and private (52% [2116/4031]; P < 0.001) hospitals than from tertiary (25% [2626/10 686]) and public (20% [2230/11 155]) hospitals. Patients undergoing coronary revascularisation procedures comprised 35% of discharges, but accounted for 56% of all program attendances. Fewer than a third of all referred patients completed OCR programs, and only 39% of available OCR program places were fully utilised. Catchment populations of programs with unused places had excess coronary mortality. CONCLUSION: There is significant underutilisation of facility-based OCR programs in Queensland. Procedures are required for identifying and referring eligible patients to existing programs and improving program compliance. Alternative OCR models are also required.     

The mammalian innate immune system: potential targets for drug development

The innate immune system is the oldest mammalian defence against invading micro-organisms and provides the first line of defence against them, however until recently a detailed understanding of its complexity has been lacking. This review describes recent advances that have been made in understanding the components of the innate immune system, including the pathogen sensing mechanisms, receptor and intracellular signalling pathways, linkage to the acquired immune system, and effectors of the innate immune response. These discoveries have created an opportunity for the development of novel drugs through the identification of targets for rational drug design. The opportunity for the development of novel anti-inflammatory and antimicrobial drugs through modulation of pro-inflammatory or antimicrobial signals within the innate immune system, are discussed. A more detailed understanding of the effectors of the innate immune system is providing an opportunity for the design of effector mimetics as novel antimicrobial drugs. The innate immune system is providing the basis for much-needed alternative approaches to controlling infection and inflammation in human medicine.     

Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT-PCR: changes in ageing

1. We investigated muscarinic receptors in the detrusor and mucosa of the human bladder body. Radioligand-binding studies with [(3)H]QNB were conducted using specimens collected from patients (36-77 years) with normal bladder function, undergoing surgery. For RT-PCR, biopsies of normal bladder were obtained from patients (30-88 years) undergoing check cystoscopy. 2. Binding of [(3)H]QNB in detrusor (n=20) was of high affinity (K(D) 77.1 (55.2-99.0) pM) and capacity (B(max) 181+/-7 fmol mg protein(-1)). Similar values were obtained in mucosa (n=6) (K(D) 100.5 (41.2-159.9) pM; B(max) 145+/-9 fmol mg protein(-1)). 3. Competition-binding experiments in detrusor membranes with muscarinic receptor antagonists including trospium, darifenacin, 4-DAMP, methoctramine, AQ-RA 741, AF-DX 116 and pirenzepine indicated a receptor population of 71% M(2), 22% M(3) and 7% M(1). In the mucosa, 75% of sites were M(2) receptors, with 25% M(3)/M(5). 4. Using RT-PCR, expression of M(1), M(2), M(3) and M(5) mRNA was demonstrated in both detrusor and mucosa. 5. The presence of a high density of mainly M(2) muscarinic receptors in the mucosa appears to be a novel finding and raises the question of their physiological significance and the source of their endogenous ligand. 6. There was a negative correlation of receptor number (B(max)) with age in detrusor muscle from male patients (P=0.02). Quantitative competitive RT-PCR demonstrated a selective age-related decrease in mRNA for muscarinic M(3) but not M(2) receptors, in both male (P<0.0001) and female (P=0.019) detrusor. These findings correspond with reports of decreased detrusor contractility with ageing.     

Ambidexterity and magical ideation

In a sample of 250 healthy undergraduate students, scores on a scale of magical ideation rose to a peak at the point of ambilaterality on a scale of hand preference, and fell away with increasing right- or left-handedness. This effect mirrors that reported by Crow, Crow, Done, and Leask (1998) who found a dip in academic abilities at the point of ambilaterality, or what they call 'the point of hemispheric indecision'. We relate these findings to genetic theories of laterality in which one allele (RS+) codes for left-cerebral dominance while the other (RS-) leaves laterality to chance. RS-- homozygotes may be susceptible to a lack of dominance, resulting in a disposition to magical ideation and an increased risk of schizophrenia, but also enhanced creativity and lateral thinking.     

Granzyme B (GraB) Autonomously Crosses the Cell Membrane and Perforin Initiates Apoptosis and GraB Nuclear Localization

Granzyme B (GraB) induces apoptosis in the presence of perforin. Perforin polymerizes in the cell membrane to form a nonspecific ion pore, but it is not known where GraB acts to initiate the events that ultimately lead to apoptosis. It has been hypothesized that GraB enters the target cell through a perforin channel and then initiates apoptosis by cleaving and activating members of the ICE/Ced-3 family of cell death proteases. To determine if GraB can enter the cell, we treated YAC-1 or HeLa cells with FITC-labeled GraB and measured intracellular fluorescence with a high sensitivity CCD camera and image analyzer. GraB was internalized and found diffusely dispersed in the cell cytoplasm within 10 min. Uptake was inhibited at low temperature (4°C) and by pretreatment with metabolic inhibitors, NaF and DNP, or cytochalasin B, a drug that both blocks microfilament formation, and FITC-GraB remained on the cell membrane localized in patches. With the simultaneous addition of perforin and FITC-GraB, no significant increase in cytoplasmic fluorescence was observed over that found in cells treated only with FITC-GraB. However, FITC-GraB was now detected in the nucleus of apoptotic cells labeling apoptotic bodies and localized areas within and along the nuclear membrane. The ability of GraB to enter cells in the absence of perforin was reexamined using anti-GraB antibody immunogold staining of ultrathin cryosections of cells incubated with GraB. Within 15 min, gold particles were detected both on the plasma membrane and in the cytoplasm of cells with some gold staining adjacent to the nuclear envelope but not in the nucleus. Cells internalizing GraB in the absence of perforin appeared morphologically normal by Hoechst staining and electron microscopy. GraB directly microinjected into the cytoplasm of B16 melanoma cells induced transient plasma membrane blebbing and nuclear coarsening but the cells did not become frankly apoptotic unless perforin was added. We conclude that GraB can enter cells autonomously but that perforin initiates the apoptotic process and the entry of GraB into the nucleus.     

Psychological stress, coping, and symptoms of disordered eating in a community sample of young Australian women

OBJECTIVE: To investigate the relationships among stress, coping, and symptoms of disordered eating in a community sample of young Australian women. METHOD: A longitudinal study design was employed. Two mail-out surveys, assessing perceived psychological stress, coping strategies, body weight dissatisfaction, dieting, and disordered eating behaviors, were completed 6 months apart by 415 young women selected from a cohort of the Women's Health Australia Study. RESULTS: Strong cross-sectional relationships among the study variables were found. Results of longitudinal analyses, however, demonstrated only tenuous relationships among stress, coping, and later symptoms of disordered eating. DISCUSSION: These results did not support the hypothesis that stress and coping strategies would predict disordered eating over time. Some evidence was found for a modest reverse relationship between stress and disordered eating. Although contrary to generally accepted theoretical models of disordered eating, these findings are consistent with those of the few previous longitudinal studies reported. Theoretical implications are discussed.     

The effect of surface modification and aprotinin on cellular injury during simulated cardiopulmonary bypass

Cardiopulmonary bypass (CPB) elicits derangements to the formed elements of blood because of the physical stresses of extracorporeal flow. Methods of reducing the impact of CPB include circuit surface modification and pharmacological supplementation. The purpose of this study was to examine the effects of aprotinin in combination with surface modification during simulated CPB. Fresh whole bovine blood was used to prime standard CPB circuits divided into four groups (N = 3): control (CTR), aprotinin 300 KIU/mL (APR), Poly (2-methoxyethylacrylate) coating (PMEA), and APR with PMEA (APR-PMEA). Physical stresses included venous reservoir negative pressure (-85 mmHg), arterial line pressure of 150 mmHg at 5 LPM, and air-blood interface, applied over a 90-minute period. Samples were drawn at the following times: 0, 10, 45, and 90 minutes. Endpoints included platelet count (PLT), plasma-free hemoglobin (PFHb), and thromboelastography (TEG). PLT did not change (138.9 +/- 15.0 vs. 102.9 +/- 21.0, p = ns) throughout the 90-minute experimental periods in any group. PFHb increased significantly (mean of 19- fold) throughout the experiment, but was not affected by any treatment. The TEG index declined in the CTR (3.6 +/- 0.4 vs. -16.2 +/- 2.9, p < .0003), PMEA (5.9 +/- 0.8 vs. -2.7 +/- 3.8, p < .02), and APR-PMEA (4.6 +/- 1.0 vs. -2.8 +/- 0.3 p < .0003) groups, but not in the APR group (3.6 +/- 2.2 vs. -1.3 +/- 3.3 p = .10). In conclusion, neither APR nor PMEA had an effect on either red cell hemolysis or PLT, but APR treatment alone significantly attenuated the derangements in coagulation induced in this extracorporeal model.