Randomized Trial of Basiliximab Induction versus Steroid Therapy in Pediatric Liver Allograft Recipients Under Tacrolimus Immunosuppression

Avoidance of corticosteroids could be beneficial after pediatric liver transplantation (LTx). To test this hypothesis, we performed a randomized prospective study to compare immunosuppression with tacrolimus (TAC) and steroids versus TAC and basiliximab (BAS) after pediatric LTx. Seventy-two patients were recruited, 36 receiving TAC and steroids and 36 TAC and BAS. The primary endpoint was the occurrence of the first rejection episode. Secondary endpoints were the cumulative incidence and severity of rejection, patient and graft survival, and incidence of adverse events. Overall 1-year patient and graft survival rates were 91.4% and 85.5% in the steroid group, and 88.6% and 80% in the BAS group (p = NS). Patients free from rejection were 87.7% in the BAS group and 67.7% in the steroid group (p = 0.036). The use of BAS was associated with a 63.6% reduction in incidence of acute rejection episodes. Overall incidence of infection was 72.3% in the steroid group and 50% in the BAS group (p = 0.035). We conclude that the combination of TAC with BAS is an alternative to TAC and steroid immunosuppression in pediatric LTx, which allows for a significant reduction in the incidence of acute rejection and infectious complications.     

Quality, evolution, and clinical implications of randomized, controlled trials on the treatment of lung cancer. A lost opportunity for meta-analysis

A review of 150 published randomized trials on the treatment of lung cancer showed serious methodological drawbacks. Handling of withdrawals (only 7 trials had no dropouts), a priori estimates of sample size (only 9 trials specified the required number of patients), blinding of randomization (only 22 trials had a satisfactory procedure), and information on eligible nonrandomized patients (only 13 studies reported it precisely) were areas of major concern. Although trial quality improved over time both in design/execution (study size estimation and analysis by prognostic factors became more frequent) and reporting (information on patients' characteristics and side effects were more thoroughly reported), their evolution was inconsistent. For non-small-cell lung cancer-despite the persistent lack of proof of efficacy of any active treatment-an untreated control arm was prematurely abandoned and a wide variety of tested regimens prevailed even in better-quality studies. Slightly more promising is the picture for small-cell lung cancer, where research indicates somewhat more reliable-though limited-progress. While clinical research in lung cancer has contributed little to defining the best standard care, we conclude that its heterogeneity makes it unlikely that quantitative meta-analysis of existing trials will be constructive.     

Oncogene-induced basement membrane invasiveness in human mammary epithelial cells

Expression of the intermediate filament protein vimentin, and loss of the cellular adhesion protein uvomorulin (E-cadherin) have been associated with increased invasiveness of established human breast cancer cell linesin vitro andin vivo. In the current study, we have further examined these relationships in oncogenically transformed human mammary epithelial cells. A normal human mammary epithelial strain, termed 184, was previously immortalized with benzo[a]pyrene, and two distinct sublines were derived (A1N4 and 184B5). These sublines were infected with retroviral vectors containing a single or two oncogenes of the nuclear, cytoplasmic, and plasma membrane-associated type (v-ras ^H, v-ras ^Ki, v -mos, SV40T and c -myc). All infectants have been previously shown to exhibit some aspects of phenotypic transformation. In the current study, cellular invasiveness was determinedin vitro using Matrigel, a reconstituted basement membrane extract. Lineage-specific differences were observed with respect to low constitutive invasiveness and invasive changes after infection withras, despite similarras-induced transformation of each line. Major effects on cellular invasiveness were observed after infection of the cells with two different oncogenes (v-ras ^H + SV40T and v -ras ^H + v -mos). In contrast, the effects of single oncogenes were only modest or negligible. All oncogenic infectants demonstrated increased attachment to laminin, but altered secretion of the 72 kDa and 92 kDa gelatinases was not associated with any aspect of malignant progression. Each of the two highly invasive double oncogene transformants were vimentinpositive and uvomorulin-negative, a phenotype indicative of the epithelial-mesenchymal transition (EMT) previously associated with invasiveness of established human breast cancer cell lines. Weakly invasive untransformed mammary epithelial cells in this study were positive for both vimentin and uvomorulin, suggesting that uvomorulin may over-ride the otherwise vimentin-associated invasiveness.     

Ropivacaine or 2% mepivacaine for lower limb peripheral nerve blocks. Study Group on Orthopedic Anesthesia of the Italian Society of Anesthesia, Analgesia, and Intensive Care

BACKGROUND: Intra- and postoperative clinical properties of sciatic-femoral nerve block performed with either ropivacaine at different concentrations or mepivacaine have been evaluated in a multicenter, randomized, blinded study. METHODS: Adult patients scheduled for foot and ankle surgery were randomized to receive combined sciatic-femoral nerve block with 225 mg of either 0.5% (n = 83), 0.75% (n = 87), or 1% (n = 86) ropivacaine, or with 500 mg of 2% mepivacaine (n = 84). A thigh tourniquet was used in all patients. Onset time, adequacy of surgical anesthesia, time to offset of nerve block, and time until first postoperative requirement for pain medication were evaluated by a blinded observer. RESULTS: The adequacy of nerve block was similar in the four treatment groups (the ratios between adequate:inadequate: failed blocks were 74:9:0 with 0.5% ropivacaine, 74:13:0 with 0.75% ropivacaine, 78:8:0 with 1% ropivacaine, and 72:12:0 with 2% mepivacaine). The onset of the block was slower with 0.5% ropivacaine than with other anesthetic solutions (P < 0.001). Regardless of the concentration, ropivacaine produced a longer motor blockade (10.5+/-3.8 h, 10.3+/-4.3 h, and 10.2+/-5.1 h with 0.5%, 0.75%, and 1% ropivacaine, respectively) than with mepivacaine (4.3+/-2.6 h; P < 0.001). The duration of postoperative analgesia was shorter after mepivacaine (5.1+/-2.7 h) than after ropivacaine (12.2+/-4.1 h, 14.3+/-5 h, and 14.5+/-3.4 h, with 0.5%, 0.75%, or 1% ropivacaine, respectively; P < 0.001). Pain relief after 0.5% ropivacaine was 14% shorter than 0.75% or 1% ropivacaine (P < 0.05). During the first 24 h after surgery, 30-37% of patients receiving ropivacaine required no analgesics compared with 10% of those receiving mepivacaine (P < 0.001). CONCLUSIONS: This study suggests that 0.75% ropivacaine is the most suitable choice of local anesthetic for combined sciatic-femoral nerve block, providing an onset similar to mepivacaine and prolonged postoperative analgesia.     

Anaesthesia for ultrasound guided oocyte retrieval: midazolam/remifentanil versus propofol/fentanyl regimens

To evaluate the quality of intra-operative anaesthesia and recovery characteristics of two different anaesthesia regimens, 60 healthy women undergoing ultrasound guided oocyte retrieval for in vitro fertilization procedures were randomly allocated to receive either a propofol/fentanyl or a midazolam/remifentanil based anaesthesia. The surgical procedure was successful in all patients and no severe side effects were reported by any patient. Four patients in the midazolam/remifentanil group (13%) would not accept the same anaesthetic procedure for further in vitro fertilization treatment due to intra-operative awareness, while all propofol/fentanyl patients were prepared to accept the same procedure again (P < 0.05). Patients in the propofol/fentanyl group required manual ventilation more frequently through a facemask than those patients treated with the midazolam/remifentanil combination (50% and 30%, respectively; P < 0.05). The time to achieve an Aldrete's score of 10 was shorter in the midazolam/remifentanil patients (2 +/- 2 min) than in those who received propofol/fentanyl (4 +/- 2 min) (P < 0.001), but no differences were observed in the time required to be 'fit to discharge' from the post-anaesthesia care unit. We conclude that the use of a midazolam/remifentanil regimen is as effective and safe as a fentanyl/propofol regimen in patients undergoing transvaginal oocyte retrieval for in vitro fertilization procedures.     

Effects of pneumoperitoneum and reverse Trendelenburg position on cardiopulmonary function in morbidly obese patients receiving laparoscopic gastric banding

We prospectively evaluated the effects of pneumoperitoneum and reverse Trendelenburg position on cardiopulmonary function in 20 ASA physical status II-III morbidly obese patients (body mass index > 35 kg m(-2)) undergoing laparoscopic gastric banding. After general anaesthesia was induced, patients' lungs were ventilated using intermittent positive pressure ventilation (at measurement times, the following parameters were used: tidal volume 12 mL kg(-1) ideal body weight, respiratory rate of 12 bpm, an inspiratory to expiratory time ratio of 1:2). Haemodynamic variables, blood gas parameters, and lung/chest compliance were recorded: in the supine position, after induction of general anaesthesia (T0, baseline) and induction of pneumoperitoneum (T1); after placing the patient in a 25 degree reverse Trendelenburg position (T2); during the surgical time (T3); before deflating the abdomen (T4); after pneumoperitoneum resolution (T5), and before the end of anaesthesia, with the patient supine (T6). The PaO2, PaO2/FiO2 ratio, and lung/chest compliance decreased during the study. After the pneumoperitoneum had been resolved, lung/chest compliance but not oxygenation parameters returned to baseline values. The arterial to end-tidal CO2 tension difference progressively increased from 0.38+/-0.3 kPa (2.85+/-2.25 mmHg) (T0) to 0.63+/-0.3 kPa (4.73+/-2.25 mmHg) (T6). In morbidly obese patients, undergoing laparoscopic gastric banding, a CO2 pneumoperitoneum markedly affected gas exchange and lung/chest compliance, while positioning the patient in a 25 degree reverse Trendelenburg position had no beneficial effects.