The relation of soy intake and isoflavone levels in nipple aspirate fluid.

Given the possible breast cancer preventive effects of isoflavones, substances with an estrogen-like structure occurring in soybeans, it is of interest to assess levels directly in the breast. The objective of this pilot study was to measure isoflavones in nipple aspirate fluid. In a pilot study with 11 women, nipple aspirate fluid and urine samples were collected at baseline and after 1 month of consuming two servings of soymilk per day. In a parallel investigation, one woman donated nipple aspirate fluid, blood, and urine on the same day after consuming different amounts of soy for 9 days. Nipple aspirate fluid was collected with an aspirator, diluted 1 : 11, and stored at -20 degrees C. Isoflavonoids in nipple aspirate fluid, serum, and urine were liquid-liquid extracted after enzymatic hydrolysis followed by liquid chromatography electrospray ionization high resolution tandem mass spectrometry analysis using triply C labeled internal isoflavonoid standards. After the 30-day soy intervention, median nipple aspirate fluid yield changed very little (P=0.47), whereas urinary isoflavonoid excretion (P=0.04) and isoflavonoid levels in nipple aspirate fluid (P=0.12) increased substantially. For the nine samples collected in one participant, isoflavonoids measured in nipple aspirate fluid, plasma, and urine were highly correlated with the number of daily soy servings and with each other. This pilot study indicates that isoflavonoids in nipple aspirate fluid are 10 times lower than in plasma and are closely related to levels of isoflavonoids in urine and plasma. These findings show that isoflavonoids are present in breast fluid and may act directly on breast tissue.     

Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

Hemorrhagic complications of oculoplastic surgery

PURPOSE: To determine the incidence and risk factors of hemorrhagic complications associated with selected oculoplastic procedures. METHODS: A prospective study was performed to document the severity of intraoperative hemorrhage and postoperative bruising in patients undergoing oculoplastic procedures. The use of anticoagulant or platelet-inhibiting medications, systemic medical conditions, patient age, patient sex, and type of procedure were examined to identify risk factors for hemorrhagic complications. RESULTS: Troublesome intraoperative bleeding prolonged surgery in 9.2% of cases. Severe bleeding with the potential to affect surgical outcome was encountered in 0.4% of procedures. There was little correlation between severity of bleeding and degree of postoperative bruising. Male sex, a history of heart disease, or age >60 years imparted a slightly greater risk of intraoperative bleeding. Age >60 years, hypertension, or recent cessation of aspirin may increase the risk of postoperative bruising. A history of previous stroke increased the risk of postoperative bleeding. There was no statistical difference in the incidence of hemorrhagic complications among patients currently treated with antiplatelet/anticoagulant agents, those who had stopped these medications before surgery, and those who were not treated with these agents. No patient had permanent sequelae related to hemorrhage. Two patients had postoperative systemic complications possibly attributable to withholding anticoagulant/antiplatelet medications in preparation for surgery. CONCLUSIONS: Although serious hemorrhagic complications may be associated with oculoplastic procedures, the incidence of these complications is low. The decision to withhold antiplatelet or anticoagulant medications before surgery should be individualized. Selected procedures can be safely performed without stopping these agents.     

Use of topical misoprostol to reduce radiation‐induced mucositis: Results of a randomized,double‐blind,placebo‐controlled trial

Radiation‐induced mucositis is an acute reaction of the mucosa of patients undergoing head and neck radiotherapy. It can have debilitating and dose‐limiting consequences. There is no consensus on an accepted intervention that significantly reduces its severity. Misoprostol is a synthetic prostaglandin E₁ analogue, with properties of a mucosal cytoprotectant. We designed a randomized, double‐blind, placebo‐controlled trial of misoprostol in patients with head and neck cancer. The aim of this study was to determine if topical misoprostol was effective in reducing the severity of radiation‐induced mucositis in patients receiving radical dose radiotherapy. The effect of this intervention on a patient’s general well‐being was also investigated. The primary end‐point of the study was the incidence of Radiation Therapy Oncology Group grade 3 mucositis. Between 1999 and 2002, 83 patients were recruited into the study at Westmead and Nepean Hospitals, Sydney. Forty‐two patients were randomized to receive misoprostol and 41 to receive a placebo. Most patients received radiotherapy in the adjuvant setting (52 of the 83) and had either an oral cavity (42 of the 83) or an oropharyngeal (16 of the 83) cancer. We could not identify any significant difference in the incidence of severe mucositis based on whether patients were allocated to receive misoprostol or placebo. There was no significant difference in the mean area under the mucositis curve (13.2 vs 16.6; P = 0.1). Patients allocated to misoprostol did report slightly increased soreness (7.6 vs 6.9; P = 0.04) and a greater use of analgesics. However, this difference did not translate into a worse feeling of general well‐being as measured by a simple visual analogue scale (5.8 vs 5.2; P = 0.3). In conclusion, we were unable to identify a reduction in radiation‐induced mucositis in patients receiving misoprostol. There is a paucity of high‐level evidence on potentially useful interventions and a continued need for new and innovative research, incorporating quality‐of‐life measurements, in patients experiencing radiation‐induced mucositis.     

DNA vaccination with vaccinia virus L1R and A33R genes protects mice against a lethal poxvirus challenge

Previously we found that passive transfer of monoclonal antibodies (MAbs) specific to either the vaccinia virus (VACV) L1R or A33R gene product protected mice from challenge with VACV. The L1R-specific MAbs, which bind the intracellular mature virion (IMV), neutralized virus in cell culture, whereas the A33R-specific MAbs, which bind extracellular enveloped virions (EEV), did not. To investigate whether a protective response could be generated by vaccination with these genes, we constructed and evaluated DNA vaccines expressing the VACV L1R and/or A33R genes under control of a cytomegalovirus promoter. Mice were vaccinated with DNA-coated gold beads by using a gene gun and then challenged with VACV (strain WR) intraperitoneally. Mice vaccinated with L1R alone developed neutralizing antibodies and were partially protected. Mice vaccinated with a combination of both genes loaded on the same gold beads developed a robust anti-A33R response; however, no neutralizing antibody response was detected, and the mice were not protected. In contrast, when mice were vaccinated with L1R and A33R loaded on different gold beads, neutralizing (presumably anti-L1R) and anti-A33R antibody responses were detected, and protection was markedly improved. Our results indicated that vaccination with both L1R and A33R proteins, intended to evoke mechanistically distinct and complementary forms of protection, was more effective than vaccination with either protein by itself.     

Chronic otitis media requiring ventilation tubes in tracheotomized ventilator dependent children

The occurrence of sinusitis and middle ear effusions has frequently been attributed to the obstruction of the sinus ostia and/or eustachian tube. In the intensive care unit setting, edema caused by the irritation from nasogastric, nasotracheal and orotracheal tubes has been associated with this pathology and has been responsible for occult sepsis in this population. Our investigation was performed to determine the risk of chronic otitis media with effusion necessitating myringotomy with tympanostomy tubes among tracheotomized, ventilator dependent children in a consecutive series of children admitted to our recently created stable ventilator unit. We retrospectively reviewed the medical records of all tracheotomized, chronically ventilator dependent children < 48 months of age who had been hospitalized in this unit from the initial opening in September 1990 to January 1993. Data collected consisted of patient demographics, gestational age, cognitive abilities, age at onset of mechanical ventilation, age at tracheostomy, age at myringotomy, presence of nasogastric and gastroenterostomy tubes and evidence of gastric-esophageal reflux. All children underwent a tracheostomy procedure subsequent to the onset of mechanical ventilation. Of these patients, 9/12 (75%) later required myringotomy with tympanostomy tube placement following the occurrence of chronic otitis media with effusion. Ventilation tubes for chronic otitis media with effusion were not required in 3 patients. Using a case control study design, we examined the need of myringotomy tubes for children requiring continuous mechanical ventilation versus those requiring night-time only ventilation. The risk of myringotomy tubes in the continuously ventilated group (9/9) was significantly greater than the risk in the intermittently ventilated group (0/3) P < 0.01. We conclude chronic otitis media with effusion is a common finding among preschool-aged children who are tracheotomized and ventilator dependent. Routine periodic ENT evaluation may be indicated in all pediatric patients who require chronic mechanical ventilation. In this specific population of children, there may be a subset of patients who would benefit from prophylactic antibiotic therapy or tympanostomy tube insertion during the duration of positive pressure ventilation. Further prospective study is warranted.