Plasmapheresis-related hypotension

Hypotension is an uncommon complication of procedures involving extracorporeal circulation, including plasmapheresis. From November 1993 to March 1999, we treated 139 patients who underwent a total of 1,137 sessions of double filtration plasmapheresis (DFP). Hypotension was defined as a systolic blood pressure (BP) < 80 mm Hg or any decrease of systolic BP with systemic reactions. A total of 17 (1.5%) episodes of hypotension were documented in 15 patients during the study period. Hypotensive episodes occurred in 2.3% of patients with inflammatory neuropathy, 1.2% of patients with myasthenia gravis, and 1.2% of patients with all other medical diseases. Involvement of the autonomic nerve system (ANS) and a low baseline BP were associated with the occurrence of hypotension. Eight (47%) of 17 episodes were symptomatic and 2 were complicated with seizure. Patients with symptomatic hypotension had a higher level of systolic BP prior to DFP and a larger drop of systolic BP and pulse rate during hypotensive attacks compared to asymptomatic patients. Most hypotensive episodes were resolved briefly after intravenous infusion of saline within 30 min. Eight (47%) of the hypotensive episodes occurred during the first session of DFP treatment. Twelve (71%) of 17 episodes occurred during the last half period of treatment; 6 of them were noted during the terminating stage of DFP. In conclusion, in this series plasmapheresis-related hypotension occurred in 1.5% of DFP sessions and had a higher prevalence in patients with ANS instability and low BP. Extra caution in monitoring BP during DFP therapy is warranted in these vulnerable patients, especially during the termination phase of the first DFP session.     

Technetium-99m tetrofosmin SPECT predicts chemotherapy response in small cell lung cancer.

The multidrug resistance gene 1 encoding human P-glycoprotein (Pgp) is thought to play an important role in the multidrug resistance of lung cancer. The purpose of this study was to predict chemotherapy response by technetium-99m tetrofosmin (Tc-99m TF) lung single photon emission computed tomography (SPECT) and compare Pgp expression in patients with untreated small cell lung cancer (SCLC). Forty patients with untreated SCLC received Tc-99m TF lung SPECT prior to chemotherapy. The chemotherapy response was evaluated in the 3rd month after completion of treatment. Immunohistochemical staining of Pgp expression was performed on multiple nonconsecutive sections of biopsy specimens. By quantitative analyses, tumor to background ratios were 1.86 +/- 0.27 and 1.17 +/- 0.26 for patients with a good and poor response, respectively (p < 0.05). All of the 20 patients with a good chemotherapy response also had a positive Tc-99m TF lung SPECT and negative Pgp expression. In contrast, only 4 of the 20 patients with a poor chemotherapy response had a positive Tc-99m TF lung SPECT. Moreover, 10 of the 20 patients with a poor chemotherapy response also had negative Pgp expression (p < 0.05). Therefore, we concluded that Tc-99m TF lung SPECT can accurately predict the chemotherapy response, and Tc-99m TF lung SPECT findings can be partially compatible with Pgp expression in patients with untreated SCLC.     

The impact of external feedback on computer-assisted learning for surgical technical skill training

BACKGROUND: Computer-assisted learning (CAL) offers a number of potential advantages for surgical technical skills teaching. The purpose of this study was to evaluate the impact of individualized external feedback on surgical skill acquisition when a CAL package is used for instruction. METHODS: Freshman and sophomore students participated in a 1-hour CAL session designed to teach them how to tie a two-handed square knot. One group received individualized external feedback during the session and the other group did not. Subjects were videotaped performing the skill before and after the session. The tapes were independently analyzed, in blinded fashion, by three surgeons. Three measures were obtained: the total time for the task, whether or not the knot was square, and the general quality of the performance using a rating scale. RESULTS: Data from 105 subjects were available for final analysis. For both groups there were significant increases in the proportion of knots that were square when the posttest performance was compared with the pretest performance but there was no difference between groups on this measure. Comparison of the performance scores demonstrated that both groups had a significant improvement after the session but the performance scores were significantly better in the group that had received feedback. CONCLUSIONS: Novices in both groups using CAL showed improvement in two of the outcomes measured, suggesting that subjects in both groups attained some degree of competence with this skill. The higher posttest performance score for the group receiving feedback demonstrates that external feedback results in a higher level of mastery when CAL is used to teach surgical technical skills.     

Comparison between double-filtration plasmapheresis and immunoadsorption plasmapheresis in the treatment of patients with myasthenia gravis

Two techniques for plasmapheresis are used in the treatment of myasthenia gravis (MG): immunoadsorption (IA) and double filtration (DR). This controlled study evaluated the differences between these techniques in clinical effects and serological changes. Five patients with generalized MG (clinical states IIb and III) were enrolled; each patient received IA and DF plasmapheresis on separate occasions. Immunosorba TR-350 with an affinity to acetylcholine receptor antibodies (AchRAb) was used for IA, while Evaflux 4A was used as the plasma fractionator for DF. Each course of treatment consisted of five sessions of apheresis. MG score, titers of AchRAb, immunoglobulins (IG), and plasma biochemistry were assessed by blinded examiners before and immediately after the entire course of treatment. Both treatments effectively ameliorated symptoms of MG. There were no significant changes in MG score between the two groups (IA vs. DF: 2.2 vs. 2.6, P>0.5). IA had a higher clearance rate of AchRAb than DF (66 % vs. 54 %, P<0.05), while DF removed more IgA (72 % vs. 21 %, P< 0.05) and IgM (89 % vs. 57 %, P<0.01) than did IA. Although IA removed AchRAb more effectively than DF, the clinical effects between these two treatments were similar. The titers of AchRAb cannot reflect the clinical severity. Some circulating factors other than AchRAb may contribute to the pathogenesis of MG. Received: 10 September 1999, Received in revised form: 7 February 2000, Accepted: 24 February 2000     

Recurrent corneal perforation and acute calcareous corneal degeneration in chronic graft-versus-host disease.

Keratoconjunctivitis sicca (KCS) is a common complication of graft-versus-host disease (GVHD), and may lead to corneal epithelial defect and melting. In contrast, recurrent corneal calcareous degeneration and perforation is rare. A 46-year-old woman developed chronic GVHD after bone marrow transplantation for aplastic anemia. Severe KCS with corneal melting and calcium deposits were noted in the left eye. Penetrating keratoplasty was performed because of corneal perforation, but poor re-epithelialization and calcium deposition recurred. Lamellar keratectomy and amniotic membrane transplantation (AMT) were performed, but acute calcareous degeneration developed with subsequent recurrence of corneal perforation. After regraft, AMT and tarsorrhaphy, the corneal graft remained clear for 3 months. However, breakdown of the corneal epithelium occurred 3 weeks after spontaneous separation of tarsorrhaphy. Six months later, corneal perforation recurred again along with exacerbation of GVHD. Regraft was performed, but the patient refused tarsorrhaphy and AMT. Poor re-epithelialization persisted after regraft. Corneal melting with impending corneal perforation ensued. Further corneal surgery was refused and the patient chose to undergo evisceration. This case demonstrates that the ocular complications of GVHD may be severe enough to lead to corneal perforation and calcareous degeneration that is recalcitrant to medical and surgical treatment.     

Rhodostomin inhibits thrombin-enhanced adhesion of ROS 17/2.8 cells through the blockade of alphavbeta3 integrin.

Osteosarcoma is a very malignant bone tumor which has a high metastatic potential and usually lead to poor prognosis. The adhesion of tumor cells to the endothelium or extracellular matrix (ECM) is an essential step in the metastatic cascade. We investigated the effect of thrombin on the adhesion activity of the osteosarcoma cell line, ROS 17/2.8. Incubation with the low concentrations of thrombin (0.01-5 U/ml, 5 min to 24 h) elevated the adhesion activity of ROS 17/2.8 to both human umbilical vein endothelial cells (HUVEC) and extracellular matrix, with the peak effect at the concentration of 0.5 U/ml for 30 min at 37 degrees C. The ROS 17/2.8 cells responded to thrombin by a peak effect of increased adhesion to HUVEC (5.5 folds vs. control) and fibronectin (4.8 folds) after thrombin pretreatment (0.5 U/ml, 30 min, 37 degrees C). Pretreatment with monoclonal antibodies against beta3 integrins, including anti-alphavbeta3, 10E5 and 7E3, effectively antagonized the thrombin-enhanced cell adhesion activity, whereas anti-alpha3beta1 and anti-alpha5beta1 did not antagonize the enhanced cell adhesion. Rhodostomin, an Arg-Gly-Asp (RGD)-containing snake venom peptide, and synthetic peptide RGDS also blocked the thrombin-enhanced ROS 17/2.8 cell adhesion. This study demonstrated that thrombin enhanced the cell adhesion of ROS 17/2.8 cells to HUVEC or ECM through an upregulation of beta3 integrins, and rhodostomin was a strong inhibitor on thrombin-enhanced cell adhesion, either to HUVEC or fibronectin substratum.     

Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications.

PURPOSE: It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >/= 3 cm. PATIENTS AND METHODS: Patients were randomly assigned, according to an institutional review board-approved phase II protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m(2) every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. RESULTS: IFP and pO(2) were measured in 54 patients at baseline and after the first CT. Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (P = .02) and improved the tumor pO(2) by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. CONCLUSION: Paclitaxel significantly decreased the IFP and increased the pO(2), whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer.