Extended therapeutic window and functional recovery after intraarterial administration of neuregulin-1 after focal ischemic stroke.

We have previously shown that neuregulin-1 (NRG-1) protects neurons from ischemic brain injury if administered before focal stroke. Here, we examined the therapeutic window and functional recovery after NRG-1 treatment in rats subjected to 90 mins of middle cerebral artery occlusion (MCAO) and 24 h of reperfusion. Neuregulin-1 (2.5 ng/kg bolus, 1.25 ng/kg/min infusion) reduced infarct volume by 89.2%+/-41.9% (mean+/-s.d.; n=8; P<0.01) if administered immediately after the onset of reperfusion. Neuroprotection was also evident if NRG-1 was administered 4 h (66.4%+/-52.6%; n=7; P<0.01) and 12 h (57.0%+/-20.8%; n=8; P<0.01) after reperfusion. Neuregulin-1 administration also resulted in a significant improvement of functional neurologic outcome compared with vehicle-treated animals (32.1%+/-5.7%; n=9; P<0.01). The neuroprotective effect of the single administration of NRG-1 was seen as long as 2 weeks after treatment. Neurons labeled with the neurodegeneration marker dye Fluoro-JadeB were observed after MCAO in the cortex, but the numbers were significantly reduced after NRG-1 treatment. These results indicate that NRG-1 is a potent neuroprotective compound with an extended therapeutic window that has practical therapeutic potential in treating individuals after ischemic brain injury.     

QALYfying the value of life.

This paper argues that the Quality Adjusted Life Year or QALY is fatally flawed as a way of priority setting in health care and of dealing with the problem of scarce resources. In addition to showing why this is so the paper sets out a view of the moral constraints that govern the allocation of health resources and suggests reasons for a new attitude to the health budget.     

Preneoplastic and neoplastic growth of xenotransplanted lung-derived human cell lines using deepithelialized rat tracheas

The human lung tumor-derived cell lines A549, Calu-1, Calu-3, HuT292, and SW900 and the transformed human bronchial epithelial cell line TBE-1, that was transfected with the v-Harvey-ras oncogene, were inoculated into deepithelialized Fisher 344 rat tracheas (5 X 10(5) cells/trachea). After the ends of the tracheas were sealed, the tracheas were transplanted into s.c. tissues of nude mice. In a parallel experiment, 1 X 10(6) cells from each of these cell lines were injected s.c. Histological examination of the tracheal transplants 2, 4, 8, 12, and 16 weeks after cell inoculation proved to be of greater usefulness than either clinical or histological observation of the s.c. injection sites. A549, Calu-1, and TBE-1 produced intratracheal neoplastic nodules as early as 2 weeks after cell inoculation. Calu-3, HuT292, and SW900 grew relatively slowly in the tracheas, and simple or stratified epithelia with slight or moderate atypia (preneoplastic lesions) were seen at 2 weeks. After the 4th week, they produced tumor nodules in the tracheal transplants, whereas no tumor cells could be seen at the s.c. injection sites. The human derivation of the cells was confirmed by in situ hybridization using human-specific DNA probes. The intratracheal inoculation and xenotransplantation of human-derived cell lines offers a time-saving alternative to the s.c. inoculation assay for tumorigenicity and is at the same time a potentially valuable approach to studying preneoplastic and neoplastic progression with human cell subpopulations.     

A case of lesser curve ulceration after combined highly selective vagotomy and abdominal aortic aneurysm resection

A 71 year old white male is reported in whom ischaemic ulceration of the lesser curve of the stomach, a variant of lesser curve necrosis, occurred after the combined procedures of highly selective vagotomy (HSV) and abdominal aortic aneurysmectomy. Other operations, particularly fundoplication and incidental splenectomy, have been implicated in the aetiology of lesser curve ischaemia, an otherwise rare complication of HSV. This case suggests that concomitant aortic surgery may also increase the risk of lesser curve ischaemia after HSV. Careful endoscopic monitoring of patients undergoing these combined procedures is therefore recommended to better define the risk.     

Tachycardia''s toll: tachycardia induced cardiomyopathy — a case study

Cardiac arrhythmias are a well known cause of mortality for patients with heart disease. However, sinus tachycardia is a more unusual arrhythmia which can lead to serious heart damage or death. Even young patients with structurally normal hearts may become gravely ill.

This case study outlines the condition of sinus tachycardia, and associated changes in heart function, altered cellular structure of the myocardium and compensatory mechanisms in the body. Treatment modalities, including electro-physiological studies and drug therapies to moderate the tachycardia and myocardial oxygen demand of the heart, are discussed. Fourteen year old ‘Ben’ was previously a well, active and outgoing youth who suddenly became critically ill. He endured weeks of hospitalisation, numerous serious complications including Torsade de pointes arrhythmia, Cheyne-Stokes respirations, nausea and dizziness during this acute phase. Despite challenges, Ben's severely compromised heart muscle recovered at a remarkable rate.     

Hydatid cyst of gall bladder.

Gall bladder hydatid cyst is a rare entity. Concurrent occurrence of gall blader hydatid cysts along with liver cysts, especially with the biliary channels clear of cysts, is very rare. We report a 27-year-old man with a gall bladder hydatid cyst that was diagnosed only after opening the resected specimen of the gall bladder.     

Comprehension of pretense in children with autism

In an attempt to tap underlying competencies, the ability of children with autism to comprehend pretend acts carried out by an experimenter was compared with that shown by controls. These acts consisted of the pouring of a pretend substance from an appropriate container onto a target figure. There was no significant difference in the groups' ability to identify the pretend substance involved, to predict the pretend outcome of the actions, or to reflect on the pretend nature of the episodes. However, the performance of controls on these latter two tasks was surprisingly poor, limiting the implications that might be drawn from the observed absence of group differences in comprehension abilities.We are very grateful to the teachers and headteachers of the following schools for their cooperation and assistance throughout the period of this research: John Worrall School, Sheffield; Doucecroft School, Kelvedon; East Hill First and Middle School, Sheffield; East Hill Second School, Sheffield; Mossbrook School, Sheffield; Priory School, Doncaster; The Rowan School, Dore; St. Mary's School, Sheffield. We also thank James Russell for his helpful comments of earlier drafts of this paper.