The relationship of radiation pneumonitis to treated lung volume in breast conservation therapy

Breast conservation therapy has become a common modality for therapy of early stage breast cancer. Most studies of primary lung irradiation correlate the risk of pneumonitis with the volume of lung treated. It is proposed that the lung volume treated during tangential radiation of the intact breast may be calculated from a measurement of the central lung distance. Central lung distance is the distance from the chest wall to the edge of the field at the central axis. This study examines whether the incidence of radiation pneumonitis indeed correlates with the lung volume treated as calculated from a measurement of the central lung distance. From January 1, 1985, through December 31, 1998, 353 patients were treated with breast conservation therapy at the University of Louisville. The charts were reviewed for any evidence of clinically significant radiation pneumonitis. The treatment films were obtained and the central lung distance ascertained. Four cases of radiation pneumonitis were identified. Three of these occurred after tangential radiation and one occurred in a retreatment field after bone marrow transplant. The overall rate of radiation pneumonitis was 1.2%. A central lung distance of less than 3 cm was found in 78.3% of patients and 21.7% had a central lung distance of three or greater. There was no correlation between central lung distance and the risk of radiation pneumonitis. Breast conservation therapy is a well-tolerated modality for treatment of early stage breast cancer. The incidence of radiation pneumonitis is very low and is usually associated with other factors in addition to the tangential field lung volume.     

Optimal utilization of donor grafts with extended criteria: a single-center experience in over 1000 liver transplants

OBJECTIVE: Severely limited organ resources mandate maximum utilization of donor allografts for orthotopic liver transplantation (OLT). This work aimed to identify factors that impact survival outcomes for extended criteria donors (ECD) and developed an ECD scoring system to facilitate graft-recipient matching and optimize utilization of ECDs. METHODS: Retrospective analysis of over 1000 primary adult OLTs at UCLA. Extended criteria (EC) considered included donor age (>55 years), donor hospital stay (>5 days), cold ischemia time (>10 hours), and warm ischemia time (>40 minutes). One point was assigned for each extended criterion. Cox proportional hazard regression model was used for multivariate analysis. RESULTS: Of 1153 allografts considered in the study, 568 organs exhibited no extended criteria (0 score), while 429, 135 and 21 donor allografts exhibited an EC score of 1, 2 and 3, respectively. Overall 1-year patient survival rates were 88%, 82%, 77% and 48% for recipients with EC scores of 0, 1, 2 and 3 respectively (P < 0.001). Adjusting for recipient age and urgency at the time of transplantation, multivariate analysis identified an ascending mortality risk ratio of 1.4 and 1.8 compared to a score of 0 for an EC score of 1, and 2 (P < 0.01) respectively. In contrast, an EC score of 3 was associated with a mortality risk ratio of 4.5 (P < 0.001). Further, advanced recipient age linearly increased the death hazard ratio, while an urgent recipient status increased the risk ratio of death by 50%. CONCLUSIONS: Extended criteria donors can be scored using readily available parameters. Optimizing perioperative variables and matching ECD allografts to appropriately selected recipients are crucial to maintain acceptable outcomes and represent a preferable alternative to both high waiting list mortality and to a potentially futile transplant that utilizes an ECD for a critically ill recipient.     

Dementia and low testosterone and bioavailable testosterone levels in men: possible increased risk

This study examines associations of serum total and bioavailable testosterone (T) with dementia in a community-based cohort of men. Study subjects (n=128; ages 65 y and older at baseline) were recruited in 1990 and followed through 2006. Dementia was assessed from the subject medical records on the basis of the criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Serum from a blood draw performed in 1994 was assayed for total and bioavailable T. Twenty-one men developed dementia over 1186 person-years of follow-up. The cumulative incidence of dementia was 14.7% in men with total T <410 ng/mL (median) and 8.0% in men with higher levels [>/=410 ng/mL; age-adjusted hazard ratio (HR)=2.09; 95% confidence interval (CI)=0.76, 5.75]. Similarly, the cumulative incidence of dementia was 18.8% in men with bioavailable T <12 ng/mL (median) and 2.2% in men with bioavailable T >/=12 ng/mL; age-adjusted HR=1.22 (95% CI=0.38, 3.87). These findings do not demonstrate a significant association between T levels and dementia. However, they suggest a need for further investigation of these potential associations.     

Biomarkers for isocyanate exposure: Synthesis of isocyanate DNA adducts

Isocyanates are important intermediates in industrial manufacturing. DNA adducts and protein adducts are important tools to biomonitor people exposed to xenobiotics. In the present work, the formation of DNA adducts deriving from 4-chlorophenyl isocyanate (4CPI) and 4-methylphenyl isocyanate (4MPI) were explored. The adducts of 4CPI and/or 4MPI with 2'-deoxyadenosine, 2'-deoxyguanosine, and 2'-deoxycytidine were synthesized and characterized by NMR and MS. For low level detection, an LC-MS/MS method was developed. The formation of DNA adducts was confirmed in in vitro reactions with DNA.     

Peptide and non-peptide bradykinin receptor antagonists: role in allergic airway disease

Kinins are proinflammatory peptides that mediate a variety of pathophysiological responses. These actions occur through stimulation of two pharmacologically distinct receptor subtypes B1 and B2. In both human and animal airways, the majority of kinin-induced effects including bronchoconstriction, increases in vascular permeability and mucus secretion and cholinergic and sensory nerve stimulation appear to be bradykinin B2-receptor mediated. Peptidic and non-peptidic receptor antagonists have been developed as potential therapeutic agents. These antagonists are effective in blocking kinin-induced effects in a variety of animal models and in some instances, have been used effectively in animal models of allergic airway disease to alleviate allergen-induced pathophysiological airway responses. This review summarizes relevant studies supporting the evidence that bradykinin B2 receptor antagonism and/or upstream inhibition of tissue kallikrein will be beneficial in the treatment of inflammatory airway diseases.