The Wellcome Trust population initiative

This paper describes what the Wellcome Trust has done and aims to do through its population initiative. The Trust is required to spend its funds to improve the physical welfare of mankind, and in this context there can be no more important issue than the rapid changes that are occurring in the human population. The Trust's first involvement was to help fund the New Delhi population summit covered by the world's scientific academics in 1993 and, following discussions with authorities in the field, initiated its funding programme in 1995. Through this programme, the Trust hopes to bring about improved understanding of the relationship between reproductive health, population growth, and sustainable development and create cadres of high quality research scientists in relevant disciplines. Uniquely, funding is available under this programme to suitably qualified applicants from any country other than the USA.      

Eccentric photorefraction: improving the predictive value and yield in detection of refractive errors

Abstract
Eccentric photorefraction (EPR) is a simple photographic technique for detecting amblyopiogenic conditions. Previous EPR studies to detect refractive errors (RE) have demonstrated high sensitivity but poor predictive value. We have established new criteria for detecting RE involving quantifying retinoscopic reflex crescent widths, thereby achieving 67% predictive value with 100% sensitivity for detecting RE ≥+ 3.5 D in a clinical study of 69 children.
Optical analysis of EPR shows that anticrescent width (light crescent-free portion of the pupil) is independent of pupil diameter. Quantifying anti-crescent widths in the above clinical trial increased the predictive value to 85%.
Schematic eye and human eye EPR studies verify the theoretical prediction that similar ability to detect refractive errors is maintained when the working distance and eccentricity (distance of light source from lens edge) are reduced.
These improvements in EPR reduce its cost and improve its yield; both are essential for its introduction as an acceptable community screening tool.     

What radiation dose for DLA-identical canine marrow grafts? [published erratum appears in Blood 1989 Feb;73(2):624]

In view of reported attempts at marrow grafting after nuclear accidents with a broad range of radiation exposures, the present study explored the total-body irradiation (TBI) conditions needed for engraftment in a canine model by using marrow from DLA-identical littermates. Previous studies have shown that such grafts are consistently successful when recipients are exposed to 920 cGy of TBI delivered at a rate of 7 cGy/min from opposing dual cobalt sources. The present TBI doses were all in the lethal range. Five dogs were administered 450 cGy; seven dogs, 600 cGy; five dogs, 700 cGy; and five dogs, 800 cGy of TBI administered at 7 cGy/min. They received a median of 3.3 x 10(8) marrow cells/kg intravenously after completion of radiation. Results showed transient allogeneic marrow engraftment in all dogs administered the lowest dose of TBI studied (450 cGy). Importantly, transient grafts permitted four of five dogs to live long enough for autologous marrow recovery to occur. At increasing radiation doses, 600, 700, and 800 cGy, the risk of graft failure lessened, with 3 of 7, 2 of 5, and 1 of 5 dogs, respectively, showing graft rejection. Fewer dogs survived with autologous marrow recovery, and more showed sustained allogeneic engraftment (4 of 7, 3 of 5, and 4 of 5 dogs, respectively). We conclude that DLA-identical littermate marrow grafts are beneficial in the setting of otherwise lethal radiation exposures, with most dogs either experiencing sustained allogeneic engraftment or surviving with autologous marrow recovery due to the extended support provided by a transient allogeneic graft.     

Constrictive pericardial disease: prognostic significance of a nonvisualized left ventricular wall

Twenty-six patients with pericardial constriction confirmed by catheterization were studied by dynamic computed tomography (CT). The posterolateral wall of the left ventricular myocardium was not detected in five patients (19.2%). None had evidence of previous myocardial infarction on electrocardiogram or levocardiogram. In 16 patients, a pericardiectomy was performed to remove pericardial constriction. All five patients with nondetectable posterolateral walls of the left ventricle died at or immediately following surgery because of acute myocardial failure. Nonvisualization of the posterolateral wall of the left ventricle in patients with constrictive pericarditis suggests the presence of myocardial fibrosis or atrophy. Surgery is an extremely high risk in these patients.     

Current strategies for retarding progression of renal disease

Physiological insights gained in the 1980s into mechanisms of disease progression in experimental chronic nephropathies established the basis for therapeutic interventions to retard the progression of chronic renal disease in humans. In the 1990s, several large-scale clinical trials have confirmed the renoprotective effects of angiotensin-converting enzyme inhibitors in diabetic and nondiabetic nephropathies. Other studies have afforded strong support for the efficacy of dietary protein restriction in certain settings and underscored the importance of blood pressure control in proteinuric individuals. These interventions form the core of current strategies designed to preserve kidney function in patients with chronic renal disease.     

Is adrenaline released by sympathetic nerves in man?

Radiotracer methods were used to measure the rates of regional release of adrenaline and noradrenaline into plasma in man. This was done as a partial test of a theory of essential hypertension pathogenesis which envisages an important cotransmitter function for neuronally released adrenaline. In healthy resting men no release of adrenaline could be detected from the heart, lungs or liver. Adrenaline was released into the right renal vein but an adrenal medullary source is suspected. With the relatively limited activation of the cardiac sympathetic outflow which accompanied mental challenge and isometric exercise, cardiac adrenaline release remained undetectable. During supine bicycle exercise, which increased cardiac noradrenaline release 10–30 fold, to a mean value of 197ng/min, cardiac adrenaline release averaged 2.36 ng/min. In two clinical conditions associated with persistently elevated plasma adrenaline concentrations, cardiac failure and adrenaline-secreting phaeochromocytoma, regional release of adrenaline was clearly evident. Thus, in normal man during exercise, and in patients with cardiac failure at rest, adrenaline is released from non-adrenal sources, and probably from sympathetic nerves. Whether neuronal adrenaline release of the degree found would be sufficient to facilitate noradrenaline release, augment sympathetically-mediated cardiovascular responses and contribute to the development of arterial hypertension remains to be tested.