Potent inhibition by ropivacaine of metastatic colon cancer SW620 cell invasion and NaV1.5 channel function.

BACKGROUND: Metastatic breast and colon cancer cells express neonatal and adult splice variants of NaV1.5 voltage-activated Na(+) channels (VASCs). Block of VASCs inhibits cell invasion. Local anaesthetics used during surgical tumour excision inhibit VASC activity on nociceptive neurones providing regional anaesthesia. Inhibition of VASCs on circulating metastatic cancer cells may also be beneficial during the perioperative period. However, ropivacaine, frequently used to provide analgesia during tumour resection, has not been tested on colon cancer cell VASC function or invasion. METHODS: We used reverse transcription-polymerase chain reaction and sequencing to identify NaV1.5 variants in the SW620 metastatic colon cancer cell line. Recombinant adult and neonatal NaV1.5 variants were expressed in human embryonic kidney cells. Voltage-clamp recordings and invasion assays were used to examine the effects of ropivacaine on recombinant NaV1.5 channels and the metastatic potential of SW620 cells, respectively. RESULTS: SW620 cells expressed adult and neonatal NaV1.5 variants, which had similar steady-state inactivation profiles, but distinctive activation curves with the neonatal variant having a V1/2 of activation 7.8 mV more depolarized than the adult variant. Ropivacaine caused a concentration-dependent block of both NaV1.5 variants, with IC50 values of 2.5 and 3.9 µM, respectively. However, the reduction in available steady-state current was selective for neonatal NaV1.5 channels. Ropivacaine inhibited SW620 invasion, with a potency similar to that of inhibition of NaV1.5 channels (3.8 µM). CONCLUSIONS: Ropivacaine is a potent inhibitor of both NaV1.5 channel activity and metastatic colon cancer cell invasion, which may be beneficial during surgical colon cancer excision.

Ileal pouch-anal anastomosis-vaginal fistula: a review.

BACKGROUND: Fistula between an ileal pouch and the vagina is an uncommon complication of ileal pouch-anal anastomosis. Its optimal management has not been determined because of its low incidence. METHODS: The literature describing such fistulas was reviewed to determine the incidence, cause, and appropriate investigation and repair of these lesions. A literature search was performed with the PubMed, MEDLINE, and EMBASE databases. Through this search we located English-language articles from 1970 to 2003 on pouch-vaginal fistulas following ileal pouch-anal anastomosis. References from these articles were searched manually for further references. RESULTS AND CONCLUSION: Pouch-vaginal fistula occurs in 6.3 (range, 3.3-15.8) percent of female patients with an ileal pouch-anal anastomosis. Sepsis and technical factors are the most common contributors. It is the cause of considerable morbidity. Management depends on the level of the fistula, the amount of pelvic scar tissue, and previous treatments. An algorithm for surgical treatment is suggested.

Xenotransplantation: consent, public health and charter issues.

There is a growing body of literature and commentary analyzing the ethical and public policy concerns associated with xenotransplantation. While this technology holds great promise to provide an almost limitless supply of organs for transplantation, there remains grave concern about possible public health ramifications. As a result, it has been recommended that patients who undergo xenotransplantations will need to agree, inter alia, to a lifetime of close health monitoring, participation in an international database and autopsy upon death. It has been suggested that this agreement would transform the nature of informed consent into a "binding contract." Though such draconian measures are understandable given the magnitude of the risks involved, would existing common law and legislation allow their implementation? This paper analyzes relevant Canadian consent and public health law in the context of the xenotransplantation. Canada is a country with a particularly rich body of informed consent jurisprudence--jurisprudence firmly rooted (rightly or not) in the ethical principle of autonomy. In this climate, many of the suggested monitoring strategies would find little support from Canadian law. Before xenotransplantations proceed, policy makers must be sensitive to the legal barriers which exist to the implementation [of] effective public health measures. Effective surveillance programs will require novel approaches to consent and the enactment of specific public health laws.

Informed consent in Canada: an empirical study.

The case of Reibl v. Hughes has significantly altered the law regarding informed consent in Canada. It might be expected, therefore, that its impact on the Canadian medical profession would be significant. However, in the first study to examine the practice of Canadian doctors in this respect, Professor Robertson concludes that the profession is largely unaware of either the decision or its importance. Further, the study examines doctors' current perceptions and opinions on the disclosure of risks to patients and the results, among others, raise serious questions regarding both the awareness and reception of important legal rulings.

An autoradiographic search for radioactive particles in the lungs of cigarette smokers.

Mucosal samples from the bifuracation of a major bronchus were examined from 23 patients undergoing diagnostic bronchoscopy. Samples were autoradiographed using a technique that avoids any contact between tissue and reagents until the end of autoradiographic exposure. The autoradiographs were scanned for a-particle tracks. No significant level of alpha -activity was detected, even in samples from heavy smokers who had continued to smoke within several hours of the bronchoscopy. The lower limit of detection of a-activity in this experiment was equivalent to about 55.5 becquerrels/kg (1,500 pCi/kg) Polonium-210. These results do not support the hypothesis presented by others that a radioactivity in particulate material of cigarette smoke contributes significantly to the association between cigarette-smoking and bronchial carcinoma.

Civil liability arising from "wrongful birth" following an unsuccessful sterilization operation.

This Article examines the question of civil liability arising, both in tort and in contract, as a result of the "wrongful birth" of a child following an unsuccessful sterilization operation. After a general overview of the concept and background of wrongful birth, the Article deals with tort liability in a sterilization-wrongful-birth action, suggesting in particular that there are four stages in the sterilization process at which a physician's conduct may fall below the standard required by law, and discussing the effect of negligence at each of the four stages. The alternative claim for breach of warranty is then examined, with emphasis on the practical difficulties involved in establishing contractual liability in this type of case. Finally, the Article discusses public policy and assessment of damages issues involved in the wrongful birth action, and evaluates the merits of some of the arguments that have been advanced under these headings--particularly the "overriding benefit" theory--to defeat claims for wrongful birth.