Roxithromycin potentiates the effects of chloroquine and mefloquine on multidrug-resistant Plasmodium falciparum in vitro.

Chloroquine (CQ) and mefloquine (MQ) are no longer potent antimalarial drugs due to the emergence of resistant Plasmodium falciparum. Combination therapy has become the standard for many regimes in overcoming drug resistance. Roxithromycin (ROM), a known p-glycoprotein inhibitor, is reported to have antimalarial activity and it is hoped it will potentiate the effects of both CQ/MQ and reverse CQ/MQ-resistance. We assayed the effects of CQ and MQ individually and in combination with ROM on synchronized P. falciparum (Dd2 strain) cultures. The IC(50) values of CQ and MQ were 60.0+/-5.0 and 16.0+/-3.0 ng/ml; these were decreased substantially when combined with ROM. Isobolograms indicate that CQ-ROM combinations were relatively more synergistic (mean FICI 0.70) than MQ-ROM (mean FICI 0.85) with their synergistic effect at par with CQ-verapamil (VRP) (mean FICI 0.64) and MQ-VRP (mean FICI 0.60) combinations. We conclude that ROM potentiates the CQ/MQ response on multidrug-resistant P. falciparum.

Epidural pain relief versus systemic opioid-based pain relief for abdominal aortic surgery.

BACKGROUND: Epidural analgesia offers greater pain relief compared to systemic opioid-based medications, but its effect on morbidity and mortality is unclear. OBJECTIVES: To assess the benefits and harms of postoperative epidural analgesia in comparison with postoperative systemic opioid-based pain relief for adult patients who underwent elective abdominal aortic surgery. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials via OVID (CENTRAL) (The Cochrane Library, Issue 3, 2004); OVID MEDLINE (1966 to July 2004); and EMBASE (1980 to June 2004). We assessed non-English language reports and contacted researchers in the field. We did not seek unpublished data. SELECTION CRITERIA: We included all randomized controlled trials comparing postoperative epidural analgesia and postoperative systemic opioid-based analgesia for adult patients who underwent elective open abdominal aortic surgery. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information and data. MAIN RESULTS: Thirteen studies involving 1224 patients met our inclusion criteria; 597 patients received epidural analgesia and 627 received systemic opioid analgesia. The epidural analgesia group showed significantly lower visual analogue scale for pain on movement (up to postoperative day three), regardless of the site of epidural catheter and epidural formulation. Postoperative duration of tracheal intubation and mechanical ventilation was significantly shorter by about 20% in the epidural analgesia group. The overall incidence of cardiovascular complication; myocardial infarction; acute respiratory failure (defined as an extended need for mechanical ventilation); gastrointestinal complication; and renal insufficiency was significantly lower in the epidural analgesia group, especially in trials that used thoracic epidural analgesia. AUTHORS' CONCLUSIONS: Epidural analgesia provides better pain relief (especially during movement) for up to three postoperative days. It reduces the duration of postoperative tracheal intubation by roughly 20%. The occurrence of prolonged postoperative mechanical ventilation, overall cardiac complication, myocardial infarction, gastric complication and renal complication was also reduced by epidural analgesia, especially thoracic. However, current evidence does not confirm the beneficial effect of epidural analgesia on postoperative mortality and other types of complications.

Tailoring the field and indication of adjuvant pelvic radiation for patients with FIGO stage Ib lymph nodes-negative cervical carcinoma following radical surgery based on the GOG score--a pilot study.

INTRODUCTION: The traditional indications for adjuvant pelvic radiotherapy (RT) for International Federation of Obstetrics and Gynecology (FIGO) stage Ib1 lymph nodes-negative cervix carcinoma following radical surgery based on histopathological factors, such as deep stromal invasion and lymphovascular space invasion (LVSI), were often inconsistently applied. The perceived risk of relapse was subjectively determined. This pilot study attempts to determine if the treatment outcome will be affected when the indication for RT is based on the Gynecologic Oncology Group (GOG) Risk Score (RS) and the field of adjuvant RT is tailored to the RS. MATERIALS AND METHODS: From 1997 to 1999, 55 patients with FIGO stage Ib1 lymph nodes-negative cervical carcinoma limited to the cervix were prescribed RT following radical surgery, based on their RS, as follows: RS <40, RT is omitted; RS >40 to <120, modified (smaller) field RT; and RS >120, standard field pelvic RT. Their incidence and site of recurrence were compared with a similar cohort of 40 patients who were treated prior to 1997. RESULTS: Prior to 1997, of the 40 patients, 10 patients were given standard field RT. There were 2 (5%) recurrent diseases. The mean duration of follow-up was 61.6 months (range, 1 to 103 months). The RS of 23 of the 30 patients who were not given RT were available. The mean RS was 22 with 5 patients having a score of >40. From 1997 onwards, of the 55 patients, 28 (51%) did not require RT, 13 (23%) were treated with modified (smaller) field RT and 14 (26%) were given standard field RT. There were 2 (3.6%) cases of relapse. The mean duration of follow-up was 36.4 months (range, 5 to 60 months). All patients with a RS of <40 did not suffer any relapse. Their survival outcomes were better when compared to patients who did not have any RT in the GOG Study. CONCLUSIONS: The results of this study indicated that postoperative adjuvant RT given to patients with a high GOG RS of >120, significantly improved their 5-year recurrence rate and disease-free survival, as compared with the similar group of patients who were without adjuvant therapy in the GOG study. Patients with a GOG risk-score of <40 may be safely spared from adjuvant pelvic RT. The current treatment protocol did not compromise the outcome in patients, compared with the use of a less precise treatment protocol in the past.

Survey of epidural analgesia management in general intensive care units in England.

BACKGROUND: The management of epidural analgesia is controversial. Many intensive care unit (ICU) patients may benefit from this form of analgesia but have one or more contraindications to its use. Sepsis, coagulopathy, insertion in a sedated, ventilated patient, and lack of consent are common problems in ICU patients. Little has been published to help guide practice in this area. I wished to establish the current practice of the management of epidural analgesia in general ICUs in England when relative or absolute contraindications occur, in order to determine the current standard of care for placement and use of epidural analgesia in ICU patients. METHODS: A postal questionnaire survey of the management of epidural analgesia in critically ill patients was sent to the named clinical director of all (216) general ICUs in England. RESULTS: Responses were received from 159 (75%) units: 89% of responding units use epidural analgesia but only 51(32%) have a written policy covering its use. Anesthetists or intensivists with an anesthetic background sited all epidural catheters; 68% of units would not site an epidural in a patient with positive blood cultures; but only 52% considered culture negative sepsis (systemic signs of sepsis with no organism isolated) to be a contraindication. Neither lack of consent nor the need for anticoagulation after the catheter had been sited were considered contraindications to inserting an epidural catheter by the majority of respondents. Although 71% of the units would remove an epidural catheter if a patient developed positive blood cultures after it had been sited, the majority of the ICUs did not consider culture negative sepsis and the need for anticoagulation contraindications to maintain a previously sited epidural. CONCLUSIONS: Practice varied considerably with little consensus. Although all the respondents use epidural analgesia in critically ill patients, the indications and contraindications to epidural analgesia remain controversial, and further research is required to help define the role of epidural analgesia in this high-risk group.