D. Walmsley

State of the art simulations of aortic haemodynamics feature full fluid-structure interaction (FSI) and coupled 0D boundary conditions. Such analyses require not only significant computational resource but also weeks to months of run time, which compromises the effectiveness of their translation to a clinical workflow. This article employs three computational fluid methodologies, of varying levels of complexity with coupled 0D boundary conditions, to simulate the haemodynamics within a patient-specific aorta. The most comprehensive model is a full FSI simulation. The simplest is a rigid walled incompressible fluid simulation while an alternative middle-ground approach employs a compressible fluid, tuned to elicit a response analogous to the compliance of the aortic wall. The results demonstrate that, in the context of certain clinical questions, the simpler analysis methods may capture the important characteristics of the flow field.

Objective: To determine whether tight control of blood pressure with either a beta blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes. Design: Randomised controlled trial comparing an angiotensin converting enzyme inhibitor (captopril) with a beta blocker (atenolol) in patients with type 2 diabetes aiming at a blood pressure of < 150/ < 85 mm Hg. Setting 20 hospital based clinics in England, Scotland, and Northern Ireland. Subjects: 1148 hypertensive patients with type 2 diabetes(mean age 56 years, mean blood pressure 160/94 mm Hg). Of the 758 patients allocated to tight control of blood pressure, 400 were allocated to captopril and 358 to atenolol. 390 patients were allocated to less tight control of blood pressure. Main outcome measures: Predefined clinical end points, fatal and non-fatal, related to diabetes, death related to diabetes, and all cause mortality. Surrogate measures of microvascular and macrovascular disease included urinary albumin excretion and retinopathy assessed by retinal photography. Results: Captopril and atenolol were equally effective in reducing blood pressure to a mean of 144/83 mm Hg and 143/81 mm Hg respectively, with a similar proportion of patients (27% and 31%) requiring three or more antihypertensive treatments. More patients in the captopril group than the atenolol group took the allocated treatment: at their last clinic visit, 78% of those allocated captopril and 65% of those allocated atenolol were taking the drug (P < 0.0001). Captopril and atenolol were equally effective in reducing the risk of macrovascular end points. Similar proportions of patients in the true groups showed deterioration in retinopathy by two grades after nine years (31% in the captopril group and 37% in the atenolol group) and developed clinical grade albuminuria greater than or equal to 300 mg/l (5% and 9%). The proportion of patients with hypoglycaemic attacks was not different between groups, but mean weight gain in the atenolol group was greater (3.4 kg v 1.6 kg). Conclusion: Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications. This study provided no evidence that either drug has any specific beneficial or deleterious effect, suggesting that blood pressure reduction in itself may be more important than the treatment used.

Objectives: To estimate the economic efficiency of tight blood pressure control, with angiotensin converting enzyme inhibitors or beta blockers, compared with less tight control in hypertensive patients with type 2 diabetes. Design: Cost effectiveness analysis incorporating within trial analysis and estimation of impact on life expectancy through use of the within trial hazards of reaching a defined clinical end point Use of resources driven by trial protocol and use of resources in standard clinical practice were both considered. Setting: 20 hospital based clinics in England, Scotland, and Northern Ireland. Subjects: 1148 hypertensive patients with type 2 diabetes from UK prospective diabetes study randomised to tight control of blood pressure (n = 758) or less tight control (n = 390). Main outcome measure: Cost effectiveness ratios based on (a) use of healthcare resources associated with tight control and less tight control and treatment of complications and (b) within trial time free from diabetes related end points, and life years gained. Results: Based an use of resources driven by trial protocol, the incremental cost effectiveness of tight control compared with less tight control was cost saving. Based on use of resources in standard clinical practice, incremental cost per extra year free from end points amounted to pound 1049 (costs and effects discounted at 6'% per year) and pound 434 (costs discounted at 6%, per year and effects not discounted). The incremental cost per life year gained was pound 720 (costs and effects discounted at 6% per year) and pound 291 (costs discounted at 6% per year and effects not discounted). Conclusions: Tight control of blood pressure in hypertensive patients with type 2 diabetes substantially reduced the cost of complications, increased the interval without complications and survival, and had a cost effectiveness ratio that compares favourably with many accepted healthcare programmes.

Muscle strips from the human detrusor and trigone were studied in vitro. The detrusor muscle contracted strongly to both cholinergic receptor stimulation with carbachol and to electrical field stimulation. There was no evidence of atropine resistance in the detrusor strips. The superficial trigone responded maximally to alpha-adrenergic receptor stimulation but also produced a significant cholinergic response. Intramural nerve stimulation in the presence of both atropine and phentolamine produced a residual non-adrenergic, non-cholinergic (NANC) response of 40% of its maximum at 5 Hz. Electrical stimulation, particularly at the lower frequencies of stimulation, produced relaxation responses in 40% of the superficial trigonal muscle strips. These relaxations were not blocked by atropine, phentolamine or propranolol, but were abolished by tetrodotoxin. The possible role of the cholinergic "input" to the superficial trigone and the importance of the NANC excitatory and inhibitory innervation in preventing vesico-ureteric reflux and and in aiding bladder neck opening is discussed.

1. Neurogenic inflammation, mediated by nociceptor C fibres, is part of the acute neurovascular response to injury producing the axon reflex flare. Laser Doppler flowmetry was used to measure the flare response induced by the electrophoresis, at various current strengths, of a ring of acetylcholine solution into dorsal foot skin. 2. Nineteen control subjects and 52 long-duration insulin-dependent (Type 1) diabetic patients of similar age (20 without complications; 19 with laser-treated retinopathy; 13 with reduced vibration perception and retinopathy) were studied in order to investigate the possible attenuation of this defence mechanism in diabetes. 3. The maximal (1 mA) flare response [control median (interquartile range): 1.55 (1.16-2.06) arbitrary units] was reduced greatly in neuropathic patients [0.37 (0.24-0.66) arbitrary units; P less than or equal to 0.001 with respect to all other groups], especially those with a previous history of foot ulceration. The flare was also reduced in some patients with retinopathy alone [1.06 (0.56-1.27) arbitrary units; P less than 0.005 with respect to control subjects]. 4. No rightward shift of the curve of hyperaemic response plotted against current strength was found, suggesting that the abnormal response was due to axonal loss rather than to dysfunction. 5. Neurogenic inflammation, mediated by small pain fibres, was markedly impaired in a group of diabetic patients at risk of foot ulceration. Furthermore, impairment of this nociceptor C fibre response can develop before clinical large-fibre neuropathy and could itself predispose to foot complications.