Thermal conductivity and energetic recoils in UO2 using a many-body potential model.

Classical molecular dynamics simulations have been performed on uranium dioxide (UO2) employing a recently developed many-body potential model. Thermal conductivities are computed for a defect free UO2 lattice and a radiation-damaged, defect containing lattice at 300 K, 1000 K and 1500 K. Defects significantly degrade the thermal conductivity of UO2 as does the presence of amorphous UO2, which has a largely temperature independent thermal conductivity of ∼1.4 Wm(-1) K(-1). The model yields a pre-melting superionic transition temperature at 2600 K, very close to the experimental value and the mechanical melting temperature of 3600 K, slightly lower than those generated with other empirical potentials. The average threshold displacement energy was calculated to be 37 eV. Although the spatial extent of a 1 keV U cascade is very similar to those generated with other empirical potentials and the number of Frenkel pairs generated is close to that from the Basak potential, the vacancy and interstitial cluster distribution is different.

Density and structural effects in the radiation tolerance of TiO2 polymorphs.

The radiation response of TiO2 has been studied using molecular dynamics. The simulations are motivated by experimental observations that the three low-pressure polymorphs, rutile, brookite and anatase, exhibit vastly different tolerances to amorphization under ion-beam irradiation. To understand the role of structure we perform large numbers of simulations using the small thermal spike method. We quantify to high statistical accuracy the number of defects created as a function of temperature and structure type, and reproduce all the main trends observed experimentally. To evaluate a hypothesis that volumetric strain relative to the amorphous phase is an important driving force for defect recovery, we perform spike simulations in which the crystalline density is varied over a wide range. Remarkably, the large differences between the polymorphs disappear once the density difference is taken into account. This finding demonstrates that density is an important factor which controls radiation tolerance in TiO2.

Impact of hospital volume on clinical and economic outcomes for esophagectomy.

BACKGROUND: Several complex surgical procedures had a reduction in mortality when they were performed at high volume centers. We hypothesized esophagectomy procedures for cancer performed at high volume hospitals in the state of Massachusetts would show a similar relationship. METHODS: Data were obtained from the Massachusetts Health Data Consortium on discharge information for all acute care hospitals in Massachusetts regardless of payer from 1992 to 2000. The influence of hospital volume was related to days in the intensive care unit, length of stay, discharge disposition, hospital mortality, and total cost. Hospitals were stratified to low volume hospitals (< 6 cases per year) and high volume hospitals (> 6 cases per year). RESULTS: One thousand one hundred ninety-three patients underwent esophagectomy during this 8-year study period in Massachusetts. Three high volume hospitals performed 56.5% of all resections (674 of 1,193). Sixty-one low volume hospitals performed 43.5% of the resections (519 of 1,193) with an average volume of only 1 case of esophagectomy per year. High volume hospitals were associated with a 2-day decrease in median length of stay (p < 0.001), a 3-day reduction in median intensive care unit stay (p < 0.001), an increased rate of home discharges (as opposed to rehabilitation hospitals) (p < 0.001), and a 3.7-fold decrease in hospital mortality (9.2% vs 2.5%; p < 0.001). The odds ratio of death at a low volume hospital was 4.3 (95% confidence interval, 2.3 to 7.7; p < 0.001). The median cost was $755 dollars greater at high volume hospitals (p = not significant). CONCLUSIONS: Hospitals that perform a high volume of esophagectomies have better results with early clinical outcomes and marked reductions in mortality compared with low volume hospitals.

Monocharged inhibitors of mast cell tryptase derived from potent and selective dibasic inhibitors.

Truncation of potent and selective dibasic inhibitors afforded monocharged inhibitors of human mast-cell tryptase. Using two classes of analogues as lead structures, several monocharged derivatives were identified with K(i) values ranging from 0.084 to 0.21 microM against the enzyme.

Dibasic inhibitors of human mast cell tryptase. Part 3: identification of a series of potent and selective inhibitors containing the benzamidine functionality.

A survey of charged groups and linkers for a series of symmetrical and unsymmetrical dibasic inhibitors is described, leading to several classes of potent and selective inhibitors. In particular, the benzamidine functionality was identified as the most potent charged group investigated.

Dibasic inhibitors of human mast cell tryptase. Part 1: synthesis and optimization of a novel class of inhibitors.

The synthesis and optimization of a novel class of reversible and active-site directed dibasic inhibitors of human mast cell tryptase are described. The compounds were shown to be both remarkably potent and selective for tryptase with Ki values for optimized inhibitors in the picomolar range.

Dibasic inhibitors of human mast cell tryptase. Part 2: structure-activity relationships and requirements for potent activity.

Detailed structure activity relationships (SARs) for a series of dibasic human tryptase inhibitors are presented. The structural requirements for potent inhibitory activity are remarkably broad with a range of core template modifications being well tolerated. Optimized inhibitors demonstrate potent anti-asthmatic activity in a sheep model of allergic asthma. APC-2059, a dibasic tryptase inhibitor with subnanomolar activity, has been advanced to phase II clinical trials for the treatment of both psoriasis and ulcerative colitis.

Long-segment colon interposition for acquired esophageal disease.

BACKGROUND: Long-segment colon interposition has been used for esophageal replacement for acquired esophageal disease. The indications for use, morbidity, and functional results of these conduits have been debated. METHODS: We reviewed the medical records, office visits, and operative reports of patients undergoing long colon interposition for acquired esophageal disease at our institution from 1956 to 1997. RESULTS: Long colon interposition was performed in 52 patients for caustic injury (n = 20), gastroesophageal disease (n = 16), previous irradiation (n = 8), primary motility disorders (n = 4), and acquired absence of the esophagus (n = 4). From 1976 to 1997, acquired diseases accounted for 62% of long colon interposition. The left colon was used in 46 patients and the right colon in 6. The in-hospital mortality rate was 4%. Early complications included graft ischemia in 5 patients, anastomotic leak in 3, and small bowel obstruction in 1. Late complications included anastomotic stenosis requiring dilation in 26 patients, with 2 requiring surgical revision, and bile reflux requiring surgical diversion in 1 patient. Swallowing function was excellent in 24% of patients, good in 66%, and poor in 10%. CONCLUSIONS: Long colon interposition can be performed safely, with acceptable long-term functional results in patients with acquired esophageal disease.

Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary resection.

BACKGROUND: The adult respiratory distress syndrome (ARDS) developing after pulmonary resection is usually a lethal complication. The etiology of this serious complication remains unknown despite many theories. Intubation, aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of treatment. Mortality rates from ARDS after pneumonectomy have been reported as high as 90% to 100%. METHODS: In 1991, nitric oxide became clinically available. We instituted an aggressive program to treat patients with ARDS after pulmonary resection. Patients were intubated and treated with standard supportive measures plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all patients had postural changes to improve ventilation/perfusion matching and management of secretions. Systemic steroids were given to half of the patients. RESULTS: Ten consecutive patients after pulmonary resection with severe ARDS (ARDS score = 3.1+/-0.04) were treated. The mean ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen at initiation of treatment was 95+/-13 mm Hg (mean +/- SEM) and improved immediately to 128+/-24 mm Hg, a 31%+/-8% improvement (p<0.05). The ratio improved steadily over the ensuing 96 hours. Chest x-rays improved in all patients and normalized in 8. No adverse reactions to nitric oxide were observed. CONCLUSIONS: We recommend the following treatment regimen for this lethal complication: intubation at the first radiographic sign of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per million); aspiration bronchoscopy and postural changes to improve management of secretions and ventilation/perfusion matching; diuresis and antibiotics; and consideration of the addition of intravenous steroid therapy.

Effects of cancer chemotherapeutic agents on endocrine organs and serum levels of estrogens, progesterone, prolactin, and luteinizing hormone.

The effects of the following cancer chemotherapeutic agents on serum hormonal levels, estrous cycles, and endocrine organs were studied in mature, normal Sprague-Dawley rats by radioimmunoassay, vaginal smear examination, and organ weight end point: estradiol mustard (NSC 112259), testosterone mustard (NSC 112260), phenoestrin (NSC 104469), methotrexate (NSC 740), 5-fluorouracil (NSC 19893), vinblastine (NSC 49842), vincristine (NSC 67574), nitrogen mustard (NSC 762), and 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC 409962). Following 2 weeks of treatment, estradiol-17beta levels were markedly elevated by all compounds except testosterone mustard and nitrogen mustard, which caused a decrease. Estrone levels were elevated by methotrexate, 5-fluorouracil, vinblastine, vincristine, nitrogen mustard, and 1,3-bis(2-chloroethyl)-1-nitrosourea, but were lowered by estradiol mustard. Progesterone levels were elevated only by estradiol mustard and testosterone mustard and were not affected by other compounds. Prolactin surge during proestrus was suppressed by phenesterin and methotrexate. Luteinizing hormone levels were lowered by methotrexate and nitrogen mustard. Estrous cycles of rats treated with estradiol mustard were arrested at proestrus, and the uterine and pituitary weights of these rats markedly increased. Uterine weight loss was significant following treatment with testosterone mustard, 5-fluorouracil, and nitrogen mustard. Thyroid weight was reduced by all compounds except methotrexate and vinblastine. Significant increases in pituitary weights occurred following treatment with all compounds except 1,3-bis(2-chloroethyl)-1-nitrosourea. The effects on ovarian and adrenal weights were minimal although significant by some compounds. Thus, in addition to their direct antitumor effects, these agents also produced changes in endocrine system which may be synergistic or antagonistic to the chemotherapy of endocrine-responsive neoplasms.