Ruthenium oligonucleotides, targeting HPV16 E6 oncogene, inhibit the growth of cervical cancer cells under illumination by a mechanism involving p53.

High-risk Human Papillomaviruses (HPV) has been found to be associated with carcinomas of the cervix, penis, vulva/vagina, anus, mouth and oro-pharynx. As the main tumorigenic effects of the HPV have been attributed to the expression of E6 and E7 genes, different gene therapy approaches have been directed to block their expression such as antisense oligonucleotides (ASO), ribozymes and small interfering RNAs. In order to develop a gene-specific therapy for HPV-related cancers, we investigated a potential therapeutic strategy of gene silencing activated under illumination. Our aim according to this antisense therapy consisted in regulating the HPV16 E6 oncogene by using an E6-ASO derivatized with a polyazaaromatic ruthenium (Ru(II)) complex (E6-Ru-ASO) able, under visible illumination, to crosslink irreversibly the targeted sequence. We examined the effects of E6-Ru-ASO on the expression of E6 and on the cell growth of cervical cancer cells. We demonstrated using HPV16(+) SiHa cervical cancer cells that E6-Ru-ASO induces after illumination, a reactivation of p53, the most important target of E6, as well as the inhibition of cell proliferation with a selective repression of E6 at the protein level. These results suggest that E6-Ru ASOs, activated under illumination and specifically targeting E6, are capable of inhibiting HPV16(+) cervical cancer cell proliferation.

A prospective randomized study of minimally invasive total knee arthroplasty compared with conventional surgery.

BACKGROUND: Despite intense debate regarding whether minimally invasive techniques for total knee arthroplasty improve clinical outcomes over standard techniques, few prospective randomized trials addressing this debate are available in the literature. We therefore designed this multicenter study to assess the overall safety and effectiveness of a minimally invasive approach without the use of computer navigation in comparison with conventional knee arthroplasty. METHODS: We prospectively randomized 134 patients (101 women and thirty-three men, with an average age of 70.1 years) to undergo surgery for total knee arthroplasty with use of either minimally invasive knee instruments (sixty-six patients) or a standard approach (sixty-eight patients). The follow-up period was one year. RESULTS: On the basis of our sample size, no significant difference was detected between the groups in any of the relevant clinical areas assessed: total range of motion, Knee Society total and function scores, and visual analog scores for pain and activities of daily living. Patients who underwent minimally invasive surgery had a longer mean surgical time (by 5.6 minutes) and had less mean blood loss (by 17 mL). Radiographic measurements demonstrated reliable implant positioning in both groups. Seven patients in each group had an adverse event related to their procedure. CONCLUSIONS: On the basis of the numbers, no significant advantage to minimally invasive total knee arthroplasty over a conventional technique was observed. Greater sample sizes and a longer follow-up period are required to fully determine the long-term safety and efficacy of this minimally invasive surgical technique.

Carvedilol overdose.

Carvedilol is a non selective beta-adrenoceptor antagonist which also causes peripheral vasodilation primarily via alpha 1-adrenergic blockade (Strein et al., 1987, McTavish et al., 1993). It has been shown effective in the treatment of mild-to-moderate hypertension and angina, and is currently under investigation in patients with congestive heart failure.

Methanol poisoning during late pregnancy.

CASE REPORT: A 26-year-old woman ingested 250 to 500 mL methanol during the 38th week of pregnancy. The initial serum methanol concentration was 230 mg/dL and formate was 33.6 mg/dL. A mild metabolic acidosis was present. As gynecologic examination and fetal monitoring failed to detect fetal distress, it was decided to give tocolytic therapy until the treatment of methanol poisoning could be achieved in the mother. Therapy included ethanol infusion, bicarbonate administration and three courses of hemodialysis. Delivery occurred six days after methanol exposure, when methanol was no longer detected in maternal blood. No further complications were noted in the mother and her newborn. To our knowledge, there is no other case of methanol poisoning during pregnancy in the literature.

[Myocardial revascularization with internal mammary artery graft: analysis of early and late post-operative respiratory morbidity]. / Revascularisation myocardique avec greffon mammaire: analyse de la morbidité respiratoire post-opératoire immédiate et tardive.

To evaluate the respiratory morbidity resulting from myocardial revascularization with internal mammary artery (IMA) graft, we reviewed 153 patients operated on between April and November 1988. There were 124 men with a mean age of 61 years. A bilateral IMA graft was used in 30 patients (20%). During the harvesting of the mammary graft, the homolateral pleura was systematically opened. Acute respiratory failure was more frequent in patients with bilateral IMA (13%) than in patients with unilateral IMA graft (3%) (p less than 0.05). Consequently, the mean duration of mechanical ventilation was longer in patients with bilateral IMA graft: 56 versus 23 hours (p less than 0.05). Lung volume measurements were altered according to a restrictive pattern. On the 9th post-operative day, forced vital capacity was reduced to 59.6% of the pre-operative value in patients with unilateral IMA and to 47.1% in patients with bilateral IMA graft (p less than 0.001). Late results were obtained in 111 patients. After a mean follow-up of 7 months, forced vital capacity was still reduced to 86.8% of the pre-operative value in patients with single IMA and to 78.1% in patients with bilateral IMA graft (p less than 0.001). In conclusion, respiratory morbidity is not negligible. Bilateral IMA grafting should generally be reserved to young patients (less than 65 years) with normal pre-operative pulmonary function tests.