Cell survival and DNA double-strand break repair following X-ray or neutron irradiation of V79 cells

We have investigated the effects of 250kVp X-rays and 2.3 MeV (mean energy) neutrons on the cell survival, DNA double-strand break (dsb) induction and repair (using the Kohn neutral elution technique) in V79 cells. The lethal effects of neutrons were shown to be significantly greater than for a similar dose of X-rays (RBE = 3.55 at 10 per cent survival). However, the RBE for dsb induction, in a dose range of 10-50 Gy, was 1. On investigating the repair of DNA dsb induced by either X-ray or neutron irradiation, clear differences in the pattern of repair were found. Both a fast and a slow component of repair were seen in both cases; the former, however, was reduced following neutron irradiation and, since the amount of slow repair was similar in both cases, this resulted in proportionally more unrejoined breaks after neutrons. These experiments were carried out with elution buffer at pH 9.6; however, when similar experiments were performed at pH 7.2 the results obtained support our earlier findings. We suggest that these differences in DNA dsb repair reflect basic differences in the nature of the lesions induced by high- and low-LET ionizing radiations.     

Reversed vein graft stenosis: early diagnosis and management.

Conscientious surveillance of intrainguinal bypass grafts is mandatory to detect vein graft stenoses, which, if uncorrected, can lead to graft occlusion. It is now widely accepted that noninvasive vascular laboratory studies are the best way to detect these lesions. However, controversy still exists over treatment, specifically whether balloon angioplasty is an acceptable substitute for surgery (patch angioplasty or short jump grafts) in the treatment of these lesions. We have always favored balloon angioplasty as primary treatment and have summarized our experience with treating 72 stenotic reversed femoropopliteal and femorotibial vein grafts, which represent 12% of 521 bypass grafts performed at our institution. Prosthetic and in situ grafts are specifically excluded from this report, as well as occluded grafts, found to have stenotic lesions after lytic therapy. The most common stenotic lesion occurred within 4 cm of the proximal anastomosis (29/72 = 40%). The other sites were near the distal anastomosis (7/72 = 10%), and in the middle of the graft (15/72 = 12%). Eighty-one percent (58/72) of the lesions were treated initially by balloon angioplasty with a 31% recurrence. Twenty-nine percent of the 14 grafts treated surgically by vein patch angioplasty or short jump grafts experienced recurrence. Overall 61% (44/72) of the stenotic grafts were treated by balloon angioplasty alone. The 5-year life-table assisted primary patency after correction of the stenotic lesion was 61%. The patency of the grafts from the time of initial bypass surgery, however, was 80%. Location of the stenosis within the graft was a major determinant of patency. Lesions in the proximal graft, proximal anastomosis, and distal graft taken as a group had significantly better patency than the midgraft and distal anastomotic lesions (5-year patency, 65% vs 48%, p less than 0.001 log rank test). We continue to recommend balloon angioplasty as primary therapy for vein graft stenosis except for those occurring in the midgraft and distal anastomosis. Fortunately, this group accounts for only 36% of lesions seen with reversed veins. Recurrent stenosis after balloon angioplasty should be repaired surgically.     

Clinical correlates of high signal lesions on magnetic resonance imaging in Alzheimer's disease

Summary The pathophysiology and clinical significance of high signal lesions, visualized on magnetic resonance imaging (MRI) in patients with Alzheimer's disease (AD), remain controversial. Since they are known to correlate with vascular disease and vascular risk factors, we reviewed the clinical correlates of periventricular high signal (PVH) and subcortical white matter lesions (WML) in a sample of 106 patients with probable AD, excluding persons with treated vascular risk factors or symptomatic cerebrovascular and cardiovascular disease. Grade 2 PVH were seen in 26 (25%) and scattered WML were identified in 29 (18%). PHV were associated with advancing age and gait disturbance. WML were associated with gait disturbance and incontinence. Neither radiologic finding was related to dementia severity. The findings suggest that these lesions are common in patients with AD even when those with evidence of cerebrovascular disease are excluded; their presence, therefore, should not preclude a diagnosis of AD. Additionally, the data suggest that HSL on MRI may be one of many risk factors associated with functional disability in persons with probable AD.     

Socio-economic differences in mortality and morbidity

In England and Wales interest in differences in health between different sectors of the community can be traced back to analyses of vital registration records in the 1840s. Increased attention in recent years to differences between socio-economic groups, in part in response to initiatives by the World Health Organisation, has again exposed the limitations of traditional data. National data on this topic are now based on the OPCS Longitudinal Study, a record linkage study as used in a number of countries. Such studies provide more reliable measures of differences, cover a wider range of social dimensions, and also allow different explanations of differences to be investigated. Analyses of differences in mortality are complemented by longitudinal analyses of differences in health and morbidity now deriving from other studies such as the birth cohort studies which provide a basis for investigating processes. The time is ripe for more effort to be put into international comparisons of differences.     

Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis

Administration of an elemental diet to rats given methotrexate (MTX), 20 mg/kg intraperitoneally (ip), results in 100% mortality from severe enterocolitis. Previous studies indicate that glutamine (GLN), which is not present in elemental diets, is the preferred oxidative substrate for the gut and may facilitate intestinal recovery after injury. This study investigated the effects of a glutamine-supplemented elemental diet (GLN-ED) on nutritional status, intestinal morphometry, bacterial translocation and survival in this lethal model of intestinal injury. Three experiments were performed. In the first experiment, rats received an intragastric elemental diet supplemented with either 2% GLN or an equivalent amount of glycine (Control). After 4 days animals received either MTX, 20 mg/kg ip, or saline ip and were killed 3 days later. The GLN-ED resulted in significantly decreased weight loss, improved nitrogen retention, and increased mucosal weight, protein, and DNA content of the jejunum and colon. In the second experiment rats were assigned to diet as in the first experiment, but all animals received MTX. Control diet animals died within 120 hrs of MTX administration. The GLN-ED group had significantly longer survival time and decreased mortality. In the third experiment animals were assigned to diet and MTX as in the first experiment. Ninety-six hrs later aortic blood cultures revealed enteric bacteremia in animals administered MTX. GLN-ED resulted in a significant reduction in the incidence of bacteremia. These experiments showed that a GLN-ED significantly improved nutritional status, decreased intestinal injury, decreased bacterial translocation, and resulted in improved survival in a lethal model of enterocolitis.