Significant disparity in base and sugar damage in DNA resulting from neutron and electron irradiation

In this study, a comparison of the effects of neutron and electron irradiation of aqueous DNA solutions was investigated to characterize potential neutron signatures in DNA damage induction. Ionizing radiation generates numerous lesions in DNA, including base and sugar lesions, lesions involving base–sugar combinations (e.g. 8,5′-cyclopurine-2′-deoxynucleosides) and DNA–protein cross-links, as well as single- and double-strand breaks and clustered damage. The characteristics of damage depend on the linear energy transfer (LET) of the incident radiation. Here we investigated DNA damage using aqueous DNA solutions in 10 mmol/l phosphate buffer from 0–80 Gy by low-LET electrons (10 Gy/min) and the specific high-LET (∼0.16 Gy/h) neutrons formed by spontaneous ²⁵²Cf decay fissions. 8-hydroxy-2′-deoxyguanosine (8-OH-dG), (5′R)-8,5′-cyclo-2′-deoxyadenosine (R-cdA) and (5′S)-8,5′-cyclo-2′-deoxyadenosine (S-cdA) were quantified using liquid chromatography–isotope-dilution tandem mass spectrometry to demonstrate a linear dose dependence for induction of 8-OH-dG by both types of radiation, although neutron irradiation was ∼50% less effective at a given dose compared with electron irradiation. Electron irradiation resulted in an exponential increase in S-cdA and R-cdA with dose, whereas neutron irradiation induced substantially less damage and the amount of damage increased only gradually with dose. Addition of 30 mmol/l 2-amino-2-(hydroxymethyl)-1,3-propanediol (TRIS), a free radical scavenger, to the DNA solution before irradiation reduced lesion induction to background levels for both types of radiation. These results provide insight into the mechanisms of DNA damage by high-LET ²⁵²Cf decay neutrons and low-LET electrons, leading to enhanced understanding of the potential biological effects of these types of irradiation.     

Evidence that postoperative pain is a mediator of the tumor-promoting effects of surgery in rats

We have previously shown in rats that the provision of analgesic doses of morphine significantly reduces the tumor-promoting effects of undergoing and recovering from surgery. Because morphine had no effect in non-operated animals, and because a single preoperative dose given hours before tumor inoculation was effective, we have suggested that it is the pain-relieving effects of the drug that underlies its beneficial impact. To support and strengthen this suggestion, two different regimens of analgesia were employed, the systemic administration of the more selective mu-agonist, fentanyl, and the intrathecal (i.t.) administration of bupivacaine plus morphine. To assess host resistance against metastasis, we used a lung clearance assay of the MADB106 mammary adenocarcinoma, a natural killer (NK)-sensitive syngeneic cell line that metastasizes only to the lungs. Female and male Fischer 344 rats were randomly assigned to one of four groups using a 2x2 experimental design: experimental laparotomy under halothane anesthesia versus anesthesia alone, by drug treatment versus vehicle. In the first in vivo experiment, fentanyl was administered 20 min before surgery (40 microg/kg subcutaneously (s.c.)), and at the end of surgery in a slow-release suspension (20 microg/kg s.c.). In the second in vivo experiment, bupivacaine (10 microg) plus morphine (20 microg) in 50 microl was administered i.t. before surgery. Surgery resulted in a 3- to 4-fold increase in the lung retention of MADB106 cells in both males and females, and the observed surgery-induced increase in lung tumor retention was reduced by more than 65% in the fentanyl-treated animals and more than 45% in the animals receiving i.t. bupivacaine plus morphine. Neither drug regimen exerted effects in the anesthesia only animals. Surgery also resulted in a significant suppression of whole blood NK activity assessed at 5 h postoperatively, the same time point at which MADB106 tumor cells were inoculated in the in vivo studies. Unlike the in vivo study, fentanyl suppressed NK activity at this time point in non-operated rats, but had no effect in operated rats. Taken together, these findings strengthen the suggestion that the management of perioperative pain is a critical factor in preventing surgery-induced decreases in host resistance against metastasis. If similar relationships between pain and metastasis occur in humans, then pain control must become a priority in the postoperative care of individuals with cancer.     

A novel treatment for chronic pancreatitis

Background Hereditary pancreatitis is an important cause of chronic pancreatitis, which may result in endocrine and exocrine failure. This may necessitate simultaneous pancreas and kidney transplant (SPK). Bladder drainage of the exocrine secretions may cause problems. Aim To report one such case and its surgical correction. Methods A 20-year-old male with insulin-dependent diabetes mellitus secondary to idiopathic chronic pancreatitis had a SPK with bladder drainage. Urological and metabolic complications secondary to the drainage of pancreatic secretions, rich in proteolytic enzymes required convertion from bladder to enteric drainage. Results He was able to discontinue his pancreatic enzyme supplements, ceased to have steatorrhoea and gained weight. He was referred to the €pean Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (€PAC), hereditary pancreatitis was confirmed by genetic analysis. Conclusion Enteric-drained pancreas transplantation is a successful treatment for exocrine as well as endocrine pancreatic failure and should be considered as a treatment option in patients with chronic pancreatitis.     

Use of educational games in the health professions: A mixed-methods study of educators' perspectives in the UK

Educational games have been shown to be effective in supporting learning, especially to reinforce knowledge, and students are generally positive about the use of games. The aim of this mixed-methods study that was conducted in the UK was to explore educators' views towards the use of educational games in the health sciences. The data were collected via semistructured interviews with 13 health educators and an online survey that was completed by 97 health educators. Three factors influence the use of classroom games: reflective practice, the impact of games on students, and the impact of logistical factors. Educators assess their own performance and the impact of the games on students when planning their use; however, large classes and the need for preparation time have a negative impact on educators' willingness to use games. Similar constraints might restrict the use of active learning strategies, such as simulation, that are crucial for enabling health professionals to develop competence. These issues require consideration when planning educational methods.     

The heart and estrogen/progestin replacement study revisited: hormone replacement therapy produced net harm, consistent with the observational data

Lower coronary event rates in women receiving hormone replacement therapy (HRT) have led to a presumption of benefit. The Heart and Estrogen/Progestin Replacement Study, a large randomized trial, observed a 1.4% first year excess of coronary events, well beyond the plausible play of chance on the expected effect. Over the duration of the study, event totals were similar, but patients treated with HRT experienced them earlier, with a net loss of patient-months of event-free survival. The point at which the lower event rate in hormone-treated patients would fully repay the first year loss, with constant rates, is almost double the trial duration (of 4.1 years). Since patients in the trial were preselected for satisfactory adherence to therapy, the net benefit in practice is likely to be even less. Had the patients in the Heart and Estrogen/Progestin Replacement Study been recruited to an observational study at various intervals over the first 5 years after starting HRT, the apparent risk reduction over 5 years would have been between 21% and 34%. A previous meta-analysis of trials of HRT for other indications also shows net harm. Women with or at high risk of coronary heart disease should not start HRT. There is a risk that women without coronary heart disease might experience even greater net harm from HRT. The late benefit is necessarily limited, as it cannot exceed the event rate. The mechanism of the early loss is unknown; if it were reduced proportionately less than the late benefit, considerable net harm could result. Arch Intern Med. 2000;160:2897-2900     

Diminished concentrations of insulin-like growth factor I in cystic fibrosis

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.