Citations

AbstractPrimary systemic amyloidosis (AL) is a fatal plasma cell disorder. Pilot data suggest survival is better in patients undergoing peripheral blood stem cell transplantation (PBSCT), but the selection process makes the apparent benefit suspect. We have reported that circulating cardiac biomarkers are the best predictors of survival outside of the transplantation setting. We now test whether cardiac troponins (cTnT and cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are prognostic in transplant recipients. In 98 patients with AL undergoing PBSCT, serum cardiac biomarkers were measured (cTnT, 98 patients; cTnI, 65 patients; and NT-proBNP, 63 patients). Elevated levels of cTnT, cTnI, and NT-proBNP were present in 14%, 43%, and 48% of patients, respectively. At 20 months median follow-up, median survival has not been reached for patients with values below the thresholds; in patients with values above the thresholds, median survival is 26.1 months, 66.1 months, and 66.1 months, respectively. Our previously reported risk systems incorporating these markers were also prognostic, notably the cTnT/NT-proBNP staging. Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT.

Background Previous studies suggest that intraoperative anesthetic care may influence postoperative pain and recovery from surgery. The authors tested the hypothesis that the addition of intrathecal analgesia to general anesthesia would improve long-term functional status and decrease pain in patients undergoing radical retropubic prostatectomy. Methods One hundred patients received either general anesthesia supplemented with intravenous fentanyl or general anesthesia preceded by intrathecal administration of bupivacaine (15 mg), clonidine (75 microg), and morphine (0.2 mg). Patients and providers were masked to treatment assignment. All patients received multimodal pain management postoperatively. Primary outcomes included pain and functional status over the first 12 postoperative weeks. Results Patients receiving intrathecal analgesia required more intravenous fluids and vasopressors intraoperatively. Pain was well controlled throughout the study (mean numerical pain scores < 3 in both groups at all times studied). Intrathecal analgesia decreased pain and supplemental intravenous morphine use over the first postoperative day but increased the frequency of pruritus. Pain and functional status after discharge from the hospital did not differ between groups. Intrathecal analgesia significantly decreased the duration of hospital stay (from 2.8 +/- 2.0 to 2.1 +/- 0.5 days; P < 0.01) as a result of five patients in the control group who stayed in the hospital more than 3 days. Conclusions The benefits of improved immediate analgesia and decreased morphine requirements resulting from intrathecal analgesia must be weighed against factors such as pruritus, increased intraoperative requirement for fluids and vasopressors, and resources needed to implement this modality. Further studies are needed to determine the significance of the decrease in duration of hospital stay.

Purpose To determine whether adding the multidrug resistance gene-1 (MDR-1) modulator valspodar (PSC 833; Novartis Pharmaceuticals, Hanover, NJ) to chemotherapy provided clinical benefit to patients with poor-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Patients and Methods A phase III randomized study was performed using valspodar plus mitoxantrone, etoposide, and cytarabine (PSC-MEC; n = 66) versus MEC (n = 63) to treat patients with relapsed or refractory AML and high-risk MDS. Results For the PSC-MEC versus MEC arms, complete response (CR) was achieved in 17% versus 25% of patients, respectively (P = not significant). For patients who had not received prior intensive chemotherapy (ie, with secondary AML or high-risk MDS), the CR rate was increased—35% versus 15% for the remaining patients (P = .018); CR rates did not differ between treatment arms. The median disease-free survival in those achieving CR was similar in the two arms (10 versus 9.3 months) as was the patients’ overall survival (4.6 versus 5.4 months). The CR rates in MDR+ (69% of patients) versus MDR− patients were similar for those receiving either chemotherapy regimen (16% versus 24%). The CR rate for unfavorable cytogenetic patients (45% of patients) was 13% compared to the remainder, 28% (P = .09). Population pharmacokinetic analysis demonstrated that the clearances of mitoxantrone and etoposide were decreased by 59% and 50%, respectively, supporting the empiric dose reductions in the PSC-MEC arm designed in anticipation of drug interactions between valspodar and the chemotherapeutic agents. Conclusion CR rates and overall survival were not improved by using PSC-MEC compared to MEC chemotherapy alone in patients with poor-risk AML or high-risk MDS.

Objective To evaluate the extent to which silicone rubber mandibular implant (Silastic; Dow Corning, Midland, Mich) pressure and placement (supraperiosteal or subperiosteal) affect underlying mandibular resorption. Design A randomized, controlled animal trial. Subjects Ten mixed-breed adult hounds. Interventions Each animal's mandible was implanted with 6 Silastic blocks, 3 inserted supraperiosteally and 3 subperiosteally. Within each grouping of 3 implants, pressure was varied from "minimum" to "moderate" to "maximum" by compressing the implant with titanium miniplates. After 4 months, the animals were killed and their mandibles sectioned for microscopic examination. Results Mandibular resorption occurred in varying degrees beneath all implants by the end of the study period. The extent of resorption was consistent with retrospective studies in humans. No statistically significant difference was found between supraperiosteal or subperiosteal placement of the implants. However, higher-pressure implants tended to produce less resorption than lower-pressure implants. Conclusions While some bone resorption seems inevitable with Silastic mandibular implants, these results would seem to suggest that the placement of implants above or below the periosteum need not be a concern for the surgeon attempting to minimize this consequence. On the other hand, increased pressure may actually decrease resorption, contrary to current assumptions.

Objectives To develop a method to quantify nasal tissue resilience, to establish the normal range for persons without nasal obstruction, and to measure the changes in tissue resilience resulting from standard open rhinoplastic techniques. Methods A new device is described that determines nasal tissue resilience. Measurements on the nasal tip were obtained in triplicate at 5 distinct anatomical sites. Normal values (N = 60) were stratified for both sexes into 3 different age groups. Preoperative and postoperative measurements were also obtained in 6 patients who underwent open rhinoplasty for airway obstruction. One patient who underwent intranasal valve repair was included for comparison. All operative patients underwent preoperative and postoperative rhinomanometric measurements. Results Across all age and sex groups the anterior septal angle is the firmest area of the nasal tip. The mean tissue resilience over the interdomal area and the midcolumella is significantly greater in men than in women. The resilience of the interdomal area exhibits an age effect, with decreasing stiffness over time. The postoperative changes seen correlate well with the placement of structural grafts during rhinoplasty. Conclusions Nasal tip support can be quantified. Normative values have been established, which allow one to identify areas of inadequate tip support in persons with nasal obstruction. Alterations in tip support resulting from surgical intervention can be quantified. Open rhinoplasty techniques are an excellent tool to restore deficiencies in nasal tip support.