Mutation analysis of RAD51D in non-BRCA1/2 ovarian and breast cancer families.

BACKGROUND: Recent data show that mutations in RAD51D have an aetiological role in ovarian carcinoma, yet mutations do not appear to be associated with an increased risk for breast cancer. We studied ovarian and breast cancer families having at least one woman affected by ovarian carcinoma, to assess the importance of RAD51D mutations in such families. METHODS: The coding region of the RAD51D gene was analysed in 175 BRCA1/2-negative families with family histories of both ovarian and breast cancer ascertained from two Canadian and two Belgian institutions. RESULTS: We identified one previously reported deleterious mutation, p.Arg186(*) (c.556C>T), and two novel variants; missense substitution p.Cys119Arg and an intronic variant c.83-26A>G. p.Arg186(*) segregated with the disease in the family and two ovarian carcinomas available for analysis showed loss of the wild-type allele, but the novel variants are likely neutral. CONCLUSION: RAD51D should be included in genetic screening of ovarian cancer families that do not have BRCA1/BRCA2 mutations. We show that mutations are more likely to be found in families with two or more ovarian cancers, or in probands with first-degree relatives with ovarian cancer, and we feel testing should be preferentially offered to affected women from such families.

The best approach to safety is to fix schools and support children and staff.

It is possible to create schools that are humane, caring places where discipline issues are minimized.

Prostate position late in the course of external beam therapy: patterns and predictors.

PURPOSE: To examine prostate and seminal vesicles position late in the course of radiation therapy and to determine the effect and predictive value of the bladder and rectum on prostate and seminal vesicles positioning. METHODS AND MATERIALS: Twenty-four patients with localized prostate cancer underwent a computerized tomography scan (CT1) before the start of radiation therapy. After 4-5 weeks of radiation therapy, a second CT scan (CT2) was obtained. All patients were scanned in the supine treatment position with instructions to maintain a full bladder. The prostate, seminal vesicles, bladder, and rectum were contoured. CT2 was aligned via fixed bony anatomy to CT1. The geometrical center and volume of each structure were obtained and directly compared. RESULTS: The prostate shifted along a diagonal axis extending from an anterior-superior position to a posterior-inferior position. The dominant shift was to a more posterior-inferior position. On average, bladder and rectal volumes decreased to 51% (+/-29%) and 82% (+/-45%) of their pretreatment values, respectively. Multiple regression analysis (MRA) revealed that bladder movement and volume change and upper rectum movement were independently associated with prostate motion (p = 0.016, p = 0. 003, and p = 0.052 respectively). CONCLUSION: Patients are often instructed to maintain a full bladder during a course of external beam radiation therapy, in the hopes of decreasing bladder and small bowel toxicity. However, our study shows that large bladder volumes late in therapy are strongly associated with posterior prostate displacement. This prostate displacement may result in marginal miss.

Pulmonary embolus after vena cava filter placement.

This report characterizes risk factors in patients who suffer pulmonary embolus (PE) after insertion of vena caval filter (VCF) and formulates an organized diagnostic and therapeutic plan of management. Three hundred eighteen patients were included in a review of patients undergoing insertion of VCF from 1989 to 1995. Ten patients (six men and four women, ages 25-72 years) from this group (3.1%) experienced PE after VCF insertion. Risk factors for deep venous thrombosis were documented in these ten patients. Venacavography was performed after diagnosis of PE. Thrombus length measured from the apex of the filter was used to determine further therapy. Thrombus 5 cm or greater in length was treated with a second VCF (VCF-2). Smaller clots were treated with anticoagulation (AC). All patients treated with AC underwent repeat vena caval study (CT scan or venacavagram) 10 days to 18 months after treatment. PE occurred from 8 days to 5.5 years after original VCF insertion. Five patients suffered PE longer than 6 months (range, 21-66 months; mean, 39 months) after VCF insertion. Venacavagrams demonstrated thrombus in all ten patients with PE. Six patients were treated with VCF-2 and four patients with AC. Dissolution of thrombus was seen on follow-up in all patients given AC. All 10 patients harbored at least two risk factors for deep venous thrombosis. Malignancy was found in only two patients. Five patients were found to have procoagulant states characterized by decreased levels of anti-thrombin III or protein C or S. No postoperative deaths or early recurrent PE occurred. One patient experienced another PE 5 years after treatment with AC when she discontinued warfarin. Contraindications to AC appeared to be self-limited, and all patients were discharged on warfarin. No significant bleeding occurred during early follow-up. Our findings confirm the reliability and low complication rate for VCF. Patients experiencing PE after insertion of VCF mandate an aggressive diagnostic approach that should include venacavography and a search for identifiable risk factors including procoagulant state. Treatment with AC and insertion of a second VCF both give favorable results. All patients appear to benefit from short- or long-term warfarin therapy, and contraindications to AC frequently are self-limited. Therapy based on clot size warrants further study.

Lymphadenopathy in celiac sprue, not necessarily a malignant disease.

A 47-year-old woman who was studied for other reasons proved to have abdominal lymphadenopathy, some nodes measuring up to 2 cm. The patient, through biopsy and other studies, was diagnosed with celiac sprue; however, on a gluten-free diet, abdominal computed tomography scans several months later showed marked reduction in the size of the mesenteric nodes.

Respiratory health in asbestos-exposed ironworkers.

This study aimed to determine the prevalence of respiratory morbidity among asbestos-exposed ironworkers and to determine the relationship between respiratory morbidity indices and length of exposure. A medical screening provided information on chest radiographic abnormalities, pulmonary function, rales, finger clubbing, and respiratory symptoms for 547 asbestos-exposed ironworkers. Union pension records furnished data on length of exposure. The study group exhibited on increased prevalence of small irregular opacities, pleural plaques, and pleural thickening on chest x-ray; reduced FEF 25-75; rales; and respiratory symptoms. After controlling for the effect of cigarette smoking and age, years since joining the ironworkers union were significantly associated with profusion, pleural thickening, pleural plaques, rales, percent predicted FVC, reduced FVC, reduced FEV1, reduced FEV1/FVC, and dyspnea grades I, II, III, and IV.

Case report 589: Use of Ostamer in fusion of lumbar spine, postoperative appearance.

In the late 1950s and early 1960s there was intense orthopedic interest in a plastic polyurethane foam (Ostamer) that could be used in the fixation of fractures, performance of arthrodesis, and in spinal fusions. It saw limited success at that time but eventually fell from favor. A patient presenting with a draining sinus in the buttock, back pain, and a history of lumbar spinal fusion with Ostamer was recently scanned in our department. The CT appearance of Ostamer and a brief review of the literature are reported.