Release of adenosine and cyclic AMP from coronary endothelium in isolated guinea pig hearts: relation to coronary flow

The coronary efflux of radioactive 3',5'-cyclic adenosine monophosphate (cAMP) and adenosine from isolated guinea pig hearts was measured following selective prelabelling of coronary endothelial adenine nucleotides with 10 nM [2,8,5'-3H] adenosine. Intracoronary infusion of adenosine and its derivatives 5'-N-ethyl-carboxamide-adenosine (NECA), (-)-N6-(R-phenyl-isopropyl)-adenosine (R-PIA), and (+)-N6-(S-phenyl-isopropyl)-adenosine (S-PIA) caused dose-dependent parallel increases in both coronary flow and the coronary efflux of radioactive cAMP with a rank order of potency: NECA greater than R-PIA greater than adenosine greater than S-PIA. In contrast, adenosine receptor stimulation of isolated cardiomyocytes in primary culture decreased the cellular release of cAMP below control levels with a rank order of potency: R-PIA greater than NECA. Under control conditions, coronary efflux of adenosine and cAMP was 34.3 +/- 2.3 and 3.9 +/- 0.8 pmol/min (mean +/- SEM, n = 6), respectively. NECA (12 microM) caused an increase in cardiac cAMP release of 3.8 times and elevated the specific radioactivity of cAMP 5 times to 63.7 +/- 6.0 Ci/mol, a value 11 times greater than the specific radioactivity of tissue ATP. Based on these findings, it was concluded that the coronary endothelium possesses adenosine A2 receptors linked to adenylate cyclase, which are activated in parallel with increases in coronary flow and that cardiomyocyte adenosine receptors are predominantly of the A1 subtype. In addition, the contribution of the coronary endothelium to total cardiac adenosine release was calculated to be 14% using the specific radioactivities of adenosine and cAMP released into the effluent perfusate.     

The importance of secondary mitral valve involvement in primary aortic valve endocarditis; the mitral kissing vegetation.

AIMS: Secondary involvement of the mitral valve is well documented in primary aortic valve endocarditis. A poorly considered, but probably important causative mechanism, involving both left-sided valves, is 'mitral kissing vegetation'. This results from large aortic vegetations prolapsing into the left ventricular outflow tract and making contact with the ventricular aspect of the anterior mitral leaflet thus causing secondary infection. METHODS AND RESULTS: In 192 consecutive patients with aortic valve endocarditis, two to 18 (7.6+/-2.6) serial transoesophageal echocardiographic examinations were analysed per patient to demonstrate the development of mitral kissing vegetation on initially competent, morphologically normal mitral leaflets. In 19 patients (9.9%) with aortic valve endocarditis, mitral kissing vegetation was diagnosed within 11.6+/-9.0 (range 1-31) days following primary transoesophageal echocardiography. In all patients with mitral kissing vegetation, vegetations attached to aortic cusps were >6 mm. On hospital admission, patients with aortic valve endocarditis plus mitral kissing vegetation presented more often with a positive sepsis score, embolic events, renal failure and had larger aortic valve vegetations (9.9+/-3.3 vs 5.7+/-2.3 mm). Prognosis of aortic valve endocarditis plus mitral kissing vegetation was unfavourable (P<0.005) when compared to patients with aortic valve endocarditis alone. CONCLUSION: In aortic valve endocarditis early echocardiographic detection of mitral kissing vegetation and timely surgery may preserve the mitral valve apparatus, and favourably influence the long-term prognosis.     

Concordance between a neuroradiologist,a consultant radiologist and trained reporting radiographers interpreting MRI head examinations: An empirical study

IntroductionThis study assessed agreement between MRI reporting radiographers and a consultant radiologist compared with an index neuroradiologist when reporting MRI head (brain/internal auditory meati [IAMs]) examinations. The effect on patient management of any discordant reports was also examined.MethodsTwo trained MRI reporting radiographers (RRs), a consultant radiologist (CR) and an index neuroradiologist (INR) reported on a random sample of 210 MRI examinations. The radiographers reported during clinical practice and the radiologists in clinical practice conditions. Two independent consultant physicians (neuro-rehabilitation and neuropsychiatry) compared these reports with the index neuroradiologist report for agreement and the clinical importance of discrepant reports.ResultsOverall observer agreement between the RRs and CR was comparable in relation to agreement with the INR: RR; 93/210 (44.3%); and the CR; 83/210 (39.4%) for all head MRI examinations (p = 0.32). For brain examinations the difference was similar: RR; 64/180 (35.6%); and CR; 54/190 (30.0%), p = 0.26. Agreement rates for the IAMs examinations were identical, 29/30 (97.7%).For all head MRI examinations (n = 210) there was a very small observed difference of <0.5% in mean agreement between the reporting radiographers and the consultant radiologist (p = 0.92) for examinations where a major disagreement would have been likely to have led to a change in patient management.ConclusionMRI reporting radiographers reported during clinical practice on MRI head examinations to a level of agreement comparable with a consultant radiologist.Implications for practiceThis is an area in which radiographers could provide additional reporting roles to the reporting service to increase capacity. Wider potential benefits include cost-effectiveness and role development/retention of radiographers.     

Improvement of oral anticoagulation therapy by INR self-management

Thromboembolic complications after valve replacement are significantly reduced if the INR is increased from 1.0 to 2.0. Hemorrhagic events increase exponentially with more intensive oral anticoagulation. In INR (patient) self-testing (PST), patients self-check their INR after being appropriately educated and supplied with a coagulometer. Patients contact their home physician if the actual INR tends to run outside an individually defined target INR corridor for correction. For patient self-management (PSM), subjects are trained to self-test their INR and to adjust the anticoagulant dose according to their anticoagulation state. The median difference between self-tested and laboratory-tested INRs was < 5.0%, indicating no significant differences between the two methods. PSM resulted in a significantly more stable oral anticoagulation therapy (OAT), which was the strongest predictor for a low complication rate after valve replacement surgery. Lower rates of thromboembolism (0.9 versus 3.6% per patient-year; pt-yr) and bleeding (4.5 versus 10.9% per pt-yr) (p < 0.001) were seen in PSM subjects than with conventional INR management. A switch from conventional to PSM resulted in a 30% reduction in complication rates in the German Experience with Low Intensity Anticoagulation (GELIA) study. After appropriate education and provision with a handy coagulometer, the vast majority of patients after valve replacement can self-check INRs and adjust the anticoagulant dosage accordingly. PSM results in a significantly more stable oral anticoagulation treatment and consequently in lower incidences of thromboembolic and bleeding events.     

Aspirin esterase of gastric mucosal origin.

The enzyme, aspirin esterase, which converts acetylsalicyclic acid to the less toxic salicyclic acid, was found to be present in gastric mucosal specimens obtained from surgically resected tissue. The enzyme was found to be stable to storage and active at two pH optima. Alcohol in the reaction mixture produced a net effect of slowing the rate of aspirin hydrolysis; this was attributable to a marked inhibitory effect on aspirin esterase activity which was not completely counteracted by the increased rate of spontaneous breakdown of aspirin by alcohol. Age, sex, or gastric disease state of the patient from whom the tissue was obtained, did not significantly alter the level of enzyme activity measured, nor were different levels obtained from body or antral mucosa. In patients with gastric ulcer, those with a previous history of regular aspirin consumption did not show significantly different levels from those without such a history. It is concluded that aspirin esterase activity of gastric mucosa is not alone a significant factor in any role acetylsalicyclic acid may play in the etiology and natural history of chronic peptic ulcer.     

Inhibition of fatty acid oxidation and decrease of oxygen consumption of working rat heart by 4-bromocrotonic acid

Nonesterified fatty acids (NEFA), glucose and lactate are major fuels for myocardial energy production. The ratio of energy produced and oxygen consumed, which can be expressed as ATP/O ratio, is different for each substrate: e.g. 3.17 for glucose and 2.83 for palmitate. Direct measurements, however, have shown that the difference of oxygen consumption is about twice as great as theoretically expected. This difference is of little significance under aerobic conditions, but may be important when oxygen supply is restricted. Numerous attempts have been made to reduce oxygen consumption by activating carbohydrate oxidation or inhibiting fatty acid metabolism. As the rate of fatty acid oxidation has been shown to depend on arterial concentrations of NEFA and albumin, this may be one point of control. Further approaches such as increasing the arterial levels of glucose, insulin and potassium, have been controversially discussed. As 4-bromocrotonic acid has been found to inhibit the fatty acid oxidation in isolated rat heart mitochondria [8], this might be an effective agent to save oxygen by reducing the rate of fatty acid oxidation in intact hearts.     

A multicentre,prospective, randomised comparison of the sliding hip screw with the Medoff sliding screw and side plate for unstable intertrochanteric hip fractures

Objective

This study aimed to compare the dynamic hip screw (DHS) and Medoff sliding plate (MSP) for unstable intertrochanteric hip fractures.

Design

A randomised, prospective trial design was used.

Setting

The study was undertaken in two level-1 trauma centres and one community hospital.

Patients/participants

A total of 163 patients with unstable intertrochanteric hip fractures (Orthopaedic Trauma Association (OTA) 31-A2) were randomised to DHS or MSP. Inclusion and exclusion criteria were designed to focus on isolated unstable intertrochanteric hip fractures in ambulatory patients.

Intervention

Randomisation was performed intra-operatively, after placement of a 135° guide wire. Follow-up assessments were performed at regular intervals for a minimum of 6 months.

Main outcome measurements

The primary outcome measure was re-operation rate. The secondary outcome was patient function, evaluated using a validated outcome measure, the Hip Fracture Functional Recovery Score. Tertiary outcomes included: mortality, hospital stay, quality of reduction and malunion rate.

Results

A total of 86 patients were randomised to DHS and 77 to MSP. The groups had similar patient demographics, pre-fracture status and in-hospital course. The quality of reduction was the same for each group, but the operative time was longer in the MSP group (61.6 vs. 50.1 min, P = 0.01). The rate of re-operation was low (3/86 in DHS and 2/77 in MSP) with no statistically significant difference. The functional outcomes were the same for both groups, with functional recovery scores at 6 months of 51.0% in the DHS arm and 49.7% in the MSP arm.

Conclusions

The two techniques produced similar results for the clinically important outcomes of the need for further surgery and functional status of the patients at 6 months’ follow-up.