Despite advances in identifying genetic markers of high risk patients and the availability of genetic testing, it remains challenging to efficiently identify women who are at hereditary risk and to manage their care appropriately. HughesRiskApps, an open-source family history collection, risk assessment, and Clinical Decision Support (CDS) software package, was developed to address the shortcomings in our ability to identify and treat the high risk population. This system is designed for use in primary care clinics, breast centers, and cancer risk clinics to collect family history and risk information and provide the necessary CDS to increase quality of care and efficiency. This paper reports on the first implementation of HughesRiskApps in the community hospital setting. HughesRiskApps was implemented at the Newton-Wellesley Hospital. Between April 1, 2007 and March 31, 2008, 32,966 analyses were performed on 25,763 individuals. Within this population, 915 (3.6%) individuals were found to be eligible for risk assessment and possible genetic testing based on the 10% risk of mutation threshold. During the first year of implementation, physicians and patients have fully accepted the system, and 3.6% of patients assessed have been referred to risk assessment and consideration of genetic testing. These early results indicate that the number of patients identified for risk assessment has increased dramatically and that the care of these patients is more efficient and likely more effective.

The American Cancer Society (ACS) guidelines define the appropriate use of MRI as an adjunct to mammography for breast cancer screening. Three risk assessment models are recommended to determine if women are at sufficient risk to warrant the use of this expensive screening tool, however, the real-world application of these models has not been explored. We sought to understand how these models behave in a community setting for women undergoing mammography screening. We conducted a retrospective analysis of 5,894 women, who received mammography screening at a community hospital and assessed their eligibility for MRI according to the ACS guidelines. Of the 5,894 women, 342 (5.8%) were eligible for MRI, but we found significant differences in the number of eligible women identified by each model. Our results indicate that these models identify very different populations, implying that the ACS guidelines deserve further development and consideration. Cancer Epidemiol Biomarkers Prev; 22(1);

Rat mast cells pretreated with the tricyclic antidepressant drug amitriptyline and stimulated with compound 48/80 secreted 60% of the total serotonin present in the cells, but only 15% of histamine, another amine stored in the same granules. Ultrastructural studies demonstrated that mast cells undergoing such differential release do not exhibit classical degranulation by compound sequential exocytosis. However, there were changes in granule shape and size, as well as alterations in many morphometric parameters consistent with secretion. Storage granules lost their homogeneity, exhibited greatly reorganized matrix and were surrounded by clear spaces which were often associated with small (0.1-0.01 microns) cytoplasmic vesicles, some of which contained electron-dense material. Secretory granules often had bud-like protrusions or were fused together in series. Quantitative autoradiography localized 3H-serotonin outside the storage granules, close to small vesicles, while staining with ruthenium red demonstrated that vesicular structures associated with differential release were not endocytotic. These results suggest that amitriptyline may inhibit regular exocytosis and permit at least serotonin to be moved selectively from storage granules to the cytosol or small vesicles from which it is eventually released.

Delta-9-tetrahydrocannabinol (THC) is an effective antiemetic as compared with placebos in patients receiving chemotherapy for cancer. In this study we compared THC with prochlorperazine (compazine) in a randomized, double-blind, crossover trial with patients who had failed to benefit from standard antiemetic therapy. Regardless of the emetic activity of the chemotherapeutic agents, there were more complete responses to THC courses (in 36 of 79 courses) than to prochlorperazine (in 16 of 78 courses). Of 25 patients who were treated with both drugs and who expressed a preference, 20 preferred THC (P = 0.005). Among patients under 20 years of age there was a higher proportion of complete responses to THC courses (15 of 20) than among older patients (21 of 59 courses; P = 0.004). Increased food intake occurred more frequently with THC (P = 0.008) and was associated with the presence of a "high." Of 36 THC courses resulting in complete antiemetic responses, 32 were associated with a high. We conclude that THC is an effective antiemetic in many patients who receive chemotherapy for cancer and for whom other antiemetics are ineffective. (N Engl J Med 302:135--138, 1980).

Positive results of investigations of the antiemetic activity of delta‐9‐tetrahydrocannabinol (THC) in patients receiving cancer chemotherapy have led to the development of levonantradol, a synthetic derivative of THC. We assessed both the antiemetic activity and toxicity of intramuscular levonantradol in patients receiving cancer chemotherapy who were refractory to conventional antiemetic therapy. An open dose‐finding study was conducted using initial doses of 0.5 mg. Doses were escalated by 0.5 mg when an incomplete response with no toxicity was observed. Of the 28 patients initially treated, 25/28 (89 per cent) achieved a complete or partial antiemetic response at doses ranging from 0.5 to 1.5 mg. There was no difference in response rate with respect to age or patient size. Of the 31 patients evaluable for toxicity, six reported none. Dysphoria, the dose‐limiting toxicity, occurred in five patients (16 per cent) at 1.0 to 1.5‐mg doses. The most commonly reported side effects were somnolence (48 per cent) and dry mouth (32 per cent). We conclude that intramuscular levonantradol is an effective antiemetic at doses as low as 0.5 mg.

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Thirty five patients were enrolled into a Phase I‐II study of oral levonantradol being tested as an antiemetic for chemotherapy patients who were refractory to the aggressive use of standard antiemetic agents. Sixty‐nine total courses were given. Dysphoric reactions (fear, anxiety, hallucinations) were the most serious side effects, and were most prevalent at the highest dose tested (2.0 mg q4h). Somnolence, a “high” feeling, hypotension were also noted. Antiemetic responses were seen at 0.5, 1.0, 1.5 and 2.0 mg dose levels: the two intermediate doses gave responses comparable to those previously reported for oral THC. It is suggested that a combination of oral and parenteral levonantradol may prove to be a very effective program to relieve the otherwise disabling problems of persistent nausea and vomiting.

Sterile inflammation of the bladder has often been associated with interstitial cystitis (IC), a urologic condition of unknown etiology, predominantly affecting young and middle-aged females, for which no effective therapy is known. Recent reports have indicated that IC is associated with an increased number of bladder mast cells. Here we report the case of a middle-aged man with chronic sterile hematuria, dysuria and lower abdominal pain associated with a high number of bladder and prostate mast cells. Following therapeutic transurethral resection of the trigone area, bladder neck and prostate, samples of bladder and prostate were examined with light and electron microscopy and contained many mast cells (about 150 cells/mm²) which were not degranulated. Nevertheless, mast cells contained many altered granules and urinary levels of histamine were elevated, implying secretion without exocytosis. These findings are discussed in the context of the pathophysiology of IC and possible therapeutic interventions.