The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation.

OBJECTIVE: Prophylactic salpingo-oophorectomy is recommended to women who carry a BRCA1 or BRCA2 mutation to reduce the risks of breast, ovarian and fallopian tube cancer. We measured the impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual functioning in women with a BRCA mutation. METHODS: Women who underwent prophylactic salpingo-oophorectomy between October 1, 2002 and June 26, 2008 for a known BRCA1 or BRCA2 mutation were invited to participate. Participants completed questionnaires before prophylactic surgery and again one year after surgery. Measures of sexual functioning and menopausal symptoms before and after surgery were compared. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy was evaluated. RESULTS: 114 women who underwent prophylactic surgery completed questionnaires before and one year after surgery. Subjects who were premenopausal at the time of surgery (n=75) experienced a significant worsening of vasomotor symptoms (hot flashes, night sweats and sweating) and a decline in sexual functioning (desire, pleasure, discomfort and habit). The increase in vasomotor symptoms and the decline in sexual functioning were mitigated by HRT, but symptoms did not return to pre-surgical levels. HRT decreased vaginal dryness and dyspareunia; however, the decrease in sexual pleasure was not alleviated by HRT. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy remained high regardless of increased vasomotor symptoms and decreased sexual function. CONCLUSIONS: Women who undergo prophylactic salpingo-oophorectomy prior to menopause experience an increase in vasomotor symptoms and a decrease in sexual functioning. These symptoms are improved by HRT, but not to pre-surgical levels.

Breast and ovarian cancer risk perception after prophylactic salpingo-oophorectomy due to an inherited mutation in the BRCA1 or BRCA2 gene.

It is often recommended that women who carry a mutation in the BRCA1 or BRCA2 gene have their ovaries and fallopian tubes removed to reduce their risk of gynecologic cancer. The aim of this study was to evaluate women's perception of their risk of breast and ovarian cancer before and after prophylactic salpingo-oophorectomy. We surveyed 127 women who carry a BRCA1 or BRCA2 mutation and who underwent prophylactic salpingo-oophorectomy at the University Health Network, Toronto. Subjects were asked to estimate their risks of breast and ovarian cancer before and after surgery. Their perceived risks of cancers were then compared with published risks, based on their mutation status. BRCA1 carriers estimated their risk of breast cancer risk to be, on average, 69% before surgery and 41% after surgery. They estimated their risk of ovarian cancer to be 55% before surgery and 11% after surgery. BRCA2 carriers estimated their risk of breast cancer to be 69% prior to surgery and 45% after surgery and their perceived risk of ovarian cancer to be 43% before surgery and 8% after surgery. Compared with published risk figures, the perceived risk of ovarian cancer before prophylactic salpingo-oophorectomy was overestimated by 47% of BRCA1 mutation carriers and by 61% of BRCA2 mutation carriers. Most women who have undergone genetic counseling and subsequently choose prophylactic salpingo-oophorectomy accurately perceive their risk of breast cancer. However, in this study, many women overestimated their risk of ovarian cancer, particularly women who carry a BRCA2 mutation.

Camptothecin-loaded films for the prevention of postsurgical adhesions.

OBJECTIVE AND DESIGN: The purpose of this work was to investigate the local application of camptothecin (CPT), a drug with anti-inflammatory, antiproliferative and antiangiogenic properties, as an inhibitor of surgical adhesion formation in rats. METHODS: The anti-adhesion properties of CPT were investigated using the cecal sidewall abrasion model in a total of 92 rats. An adhesion score for each animal was obtained based on the strength and extent of the adhesions. Significance was determined by Students t-test and p values less than 0.05 were considered significant. TREATMENT: The drug was administered by application of carbodiimide crosslinked hyaluronic acid (HA) films containing CPT at concentrations of 0, 0.6, 2.5 and 7.5% w/w at the site of surgical injury. The HA films were characterized by in vitro measurements of drug release rates. RESULTS: In this model the application of HA films alone, or 0, 0.6, 2.5 or 7.5% w/w CPT-loaded HA films, had a significant effect in reducing the mean strength and area of adhesions (3.8 +/- 2.7, 5.6 +/- 0.7, 1.3 +/- 0.7, 0.9 +/- 0.8, 0.7 +/- 1.0, respectively) when compared to those animals in which no film was placed (8.4 +/- 2.5). In addition, a significant difference was observed in the effect of 0.6, 2.5 and 7.5% w/w CPT-loaded films when compared to the HA or 0% CPT-loaded films (p < 0.05). No toxicity was observed in the rats following administration of these films. CONCLUSIONS: CPT loaded films inhibited the formation of adhesions in the rat cecal sidewall abrasion model. HA crosslinked with 2 mM carbodiimide and containing 20% w/w glycerol and 0.6, 2.5 or 7.5% w/w CPT are flexible, mucoadhesive, biocompatible controlled release films that can be used to prevent adhesion formation.

Neutrophil activation by plasma opsonized polymeric microspheres: inhibitory effect of pluronic F127.

The phagocytosis of drug-loaded polymeric microspheres by white blood cells, such as neutrophils or mononuclear cells, represents the major clearance mechanism by which this foreign material is eliminated from the body. The process of phagocytosis requires the activation of the white blood cells by the microsphere surface, followed by binding and engulfment. Phagocytosis may result in the removal of the microspheres from the blood or the disease site and an inflammatory response. Therefore, we have studied the level of neutrophil activation by microspheres ( +/- opsonization) manufactured from various biomaterials or polymers. Polymer microspheres with equivalent size distributions were made from poly (DL-lactic acid) (PLA), poly(epsilon-caprolactone) (PCL), poly(methyl methacrylate) (PMMA) or a 50 : 50 blend of PLA: poly(ethylene-co-vinyl acetate) (PLA: EVA). Neutrophils were isolated from human blood and activation of these cells by microspheres was measured by chemiluminescence (CL). All four types of microspheres induced only low levels of CL, however these levels were enhanced significantly if the microspheres were pretreated with plasma or IgG suggesting an opsonization effect. The adsorption of IgG or proteins from plasma was confirmed by polyacrylamide gel electrophoresis (SDS-PAGE). The poloxamer Pluronic F127 inhibited the opsonization effect of IgG and plasma on all four types of microspheres and inhibited protein adsorption as measured by SDS-PAGE. Since neutrophil activation is part of the inflammation process in vivo, these in vitro data suggest that all four types of microspheres are likely to be inflammatory if injected into body compartments containing plasma-derived fluids. Pretreatment of the microspheres with Pluronic F127 may reduce the inflammatory potential of the microspheres.

Toxicological findings in military aircraft fatalities from 1986-1990.

Toxicological findings in all military aircraft fatalities investigated by the Division of Forensic Toxicology at the Armed Forces Institute of Pathology from 1986-1990 are presented. Carbon monoxide saturation levels greater than 10% were found in 4% of the 535 cases where appropriate specimens were collected. Positive ethanol findings were more indicative of postmortem formation than antemortem consumption. In only 1 case were abused drugs (cannabinoids in a passenger) detected. Other drugs identified included nicotine, chloroquine and over-the-counter analgesic agents, antihistamines and sympathomimetic drugs.

Fire deaths in aircraft without the crashworthy fuel system.

Cases reported to the Armed Forces Institute of Pathology were examined for occupants of helicopters without the crashworthy fuel system (CWFS) who survived crashes but died as a result of postcrash fires. There were 16 fire deaths in the 9 such accidents which occurred between January 1976 and April 1984. All of these victims would have survived if there had been no postcrash fire. Partial body destruction by fire probably prevented inclusion of many other cases. The dramatic reduction in fire deaths and injuries due to installation of the CWFS in Army helicopters is discussed. The author concludes that fire deaths and injuries in aircraft accidents could almost be eliminated by fitting current and future aircraft with the CWFS.