RNAi-mediated knockdown of the voltage gated sodium ion channel TcNav causes mortality in Tribolium castaneum.

The voltage-gated sodium ion channel (VGSC) belongs to the largest superfamily of ion channels. Since VGSCs play key roles in physiological processes they are major targets for effective insecticides. RNA interference (RNAi) is widely used to analyse gene function, but recently, it has shown potential to contribute to novel strategies for selectively controlling agricultural insect pests. The current study evaluates the delivery of dsRNA targeted to the sodium ion channel paralytic A (TcNav) gene in Tribolium castaneum as a viable means of controlling this insect pest. Delivery of TcNav dsRNA caused severe developmental arrest with larval mortalities up to 73% post injection of dsRNA. Injected larvae showed significant (p < 0.05) knockdown in gene expression between 30-60%. Expression was also significantly (p < 0.05) reduced in pupae following injection causing 30% and 42% knockdown for early and late pupal stages, respectively. Oral delivery of dsRNA caused dose-dependant mortalities of between 19 and 51.34%; this was accompanied by significant (p < 0.05) knockdown in gene expression following 3 days of continuous feeding. The majority of larvae injected with, or fed, dsRNA died during the final larval stage prior to pupation. This work provides evidence of a viable RNAi-based strategy for insect control.

neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.

PURPOSE: It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS: A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION: neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.

Primary colorectal anastomosis with the intracolonic bypass tube.

BACKGROUND: Intracolonic bypass with primary colocolonic or colorectal anastomosis may be an effective option in the operative management of complicated colonic disease when adequate bowel preparation is not possible. A pliable latex tube is anchored to mucosa and submucosa 3 centimeters proximal to a site of colocolonic anastomosis and later spontaneously evacuated by way of the rectum. METHODS: Twenty-nine consecutive patents who required urgent colorectal operations in the presence of unprepared bowel underwent left colon resection with intracolonic bypass and primary anastomosis. These patients would have otherwise undergone multistage procedures for the management of the colorectal disorders. Demographic data, APACHE II scores, and type and frequency of complications were recorded. RESULTS: Between July 1, 1990, and June 30, 1991, 31 patients were eligible for entry in the study. Two patients ultimately had contraindications for the use of intracolonic bypass. The causes encountered included complicated diverticular disease, colonic carcinoma, sigmoid volvulus, and iatrogenic colorectal injury. Complications included wound infection (7), myocardial infarction (2), prolonged ileus (1), deep vein thrombosis (2), and anastomotic leak (2). Postoperative myocardial infarction and subsequent multiorgan system failure were responsible for the only death in this study. CONCLUSIONS: Intracolonic bypass permits a safe primary anastomosis where multistage procedures would otherwise be required. Avoidance of colostomy and the attendant socioeconomic benefits warrants further study of this method.

Primary osteomyelitis of the sternum due to Salmonella hirschfeldii.

The case of a 71 year-old man with primary osteomyelitis of the sternum caused by Salmonella hirschfeldii is reported. The diagnosis was confirmed by culture, the bony defect was curetted to remove all dead bone and the patient was successfully treated with 6 weeks of high-dose ampicillin (2 g q6h). The treatment is particularly important because inadequate treatment may result in death and overtreatment may cause deformity and instability of the chest wall. Primary osteomyelitis of the sternum is a rare entity and this is apparently the first such case to be reported in the English literature.