Autoimmune thyroid disease after renal transplantation using depletional induction with alemtuzumab.
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Adult↗
Biomedical subjects
S J Swanson
Publications and source records attributed to S J Swanson.
Acute renal allograft rejection following pegylated IFN-alpha treatment for chronic HCV in a repeat allograft recipient on hemodialysis: a case report.
Interferon alpha (IFN-alpha) can be effective therapy for patients with chronic kidney disease who have chronic hepatitis C (HCV). However, acute allograft rejection has been reported in association with IFN-alpha following kidney transplantation, and therefore IFN therapy is recommended prior to, rather than after, kidney transplantation whenever feasible. The special case of repeat allograft recipients who contract HCV after the first transplantation presents special difficulties. This report features the case of a repeat allograft recipient who presented with neutropenic fevers after 5 months of pegylated IFN-alpha therapy, initiated 6 months following the functional loss of his third graft and the reinitiation of hemodialysis (HD). Physical exam, radiographic and laboratory findings led to allograft nephrectomy. The pathologic findings supported a diagnosis of acute-on-chronic rejection. This represents a rare case of IFN-alpha induced rejection following allograft failure and return to HD in a repeat allograft recipient. It also calls attention to the need for a high index of suspicion for the development of allograft rejection, which may require allograft nephrectomy even after allograft 'failure'.
Graft Rejection↗
Characterization of an immune response.
The characterization of any detected antibodies provides detailed information that can be critical to understanding the significance of an immune response. The BIAcore immunoassay provides a straightforward means of characterizing many aspects of the immune response including antibody concentration, specificity, binding affinity, and the presence of isotypes. One important aspect of the immune response is determination of neutralizing capability, which requires a biological assay. The ultimate clinical significance of an immune response can only be fully understood when data from antibody characterization are coupled with clinical data from the patient. Some of the factors that can contribute to the clinical significance of an immune response are: (i) magnitude of the immune response (concentration of antibodies detected); (ii) duration of the immune response (continuous antibody production or sporadic and not sustained); (iii) correlation with any adverse events; (iv) correlation with a change in pharmacokinetics (either mediating sustained circulation or enhanced clearance of the drug); (v) biological neutralization of the drug; (vi) biological neutralization of an endogenous protein. Full characterization of the immune response requires the incorporation of antibody assays, pharmacokinetic assays, and clinical data.
Animals↗
Use of preoperative functional neuroimaging to predict language deficits from epilepsy surgery.
BACKGROUND: Left anterior temporal lobectomy (L-ATL) may be complicated by confrontation naming deficits. OBJECTIVE: To determine whether preoperative fMRI predicts such deficits in patients with epilepsy undergoing L-ATL. METHODS: Twenty-four patients with L-ATL underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language dominance, and pre- and postoperative neuropsychological testing. fMRI laterality indexes (LIs), reflecting the interhemispheric difference between activated volumes in left and right homologous regions of interest, were calculated for each patient. Relationships between the fMRI LI, Wada language dominance, and naming outcome were examined. RESULTS: Both the fMRI LI (p < 0.001) and the Wada test (p < 0.05) were predictive of naming outcome. fMRI showed 100% sensitivity and 73% specificity in predicting significant naming decline. Both fMRI and the Wada test were more predictive than age at seizure onset or preoperative naming performance. CONCLUSIONS: Preoperative fMRI predicted naming decline in patients undergoing left anterior temporal lobectomy surgery.
Adult↗
New technologies for the detection of antibodies to therapeutic proteins.
The determination of antibody formation in response to a therapeutic product requires that a variety of data be evaluated. In addition to examining immuno-assay and bioassay results, it is important to determine any clinical relevance. By also examining pharmacokinetic data as well as other clinical results, an evaluation can be made as to whether any clinically relevant antibodies were generated. To help in this evaluation, it is important to fully characterize the antibodies that are generated. Both the BIAcore and IGEN platforms are powerful tools for determining if antibodies have been produced in a subject The BIAcore is also able to characterize these antibodies as to isotype, relative concentration, and relative affinity. The bioassay result can identify serum samples that contain an agent capable of inhibiting a biological effect of a drug. When combined with the results of an immuno-assay, it is possible to determine if the antibodies are capable of neutralizing the drug.
Antibodies↗
Spatial variation of plasma flow in the oxazolone-stimulated microcirculation.
INTRODUCTION: In cutaneous lymphocytic inflammation, enhanced regional blood flow is suggested by persistent erythema and warmth. Direct assessment of the microcirculation, however, has been limited by tissue edema and skin thickness. METHODS: To assess the microcirculatory adaptations to the epicutaneous antigen oxazolone, we studied the first pass kinetics and microvascular topography of the inflammatory skin microcirculation using a specially adapted epi-illumination intravital microscopy system. The fluorescence intravital videomicroscopy and streaming image acquisition of fluorescein-labeled dextran (approximately 500,000 MW) injections were used to assess changes in plasma flow. RESULTS: Direct plasma tracer injections of both the oxazolone-stimulated and control microcirculation demonstrated comparable transit times (leading edge and intensity-weighted peak times) from the carotid artery to the superficial vascular plexus (p > 0.05). In contrast to transit times, continuous infusion of the plasma tracer demonstrated a significant increase in the delivery of the fluorescein-labeled dextran to the oxazolone-stimulated microcirculation. Quantitative morphometry of intravital microscopic images demonstrated a 2.2-fold increase in the mean diameter of vessels in the superficial vascular plexus (p < 0.01). Further, fluorescence intensity mapping indicated that the increase was associated with increased perfusion of focal regions of the superficial vascular plexus (p < 0.001). CONCLUSIONS: These results indicate that the oxazolone-stimulated adaptations of the inflammatory microcirculation include both microvascular dilatation and the redistribution of plasma flow.
Animals↗
Impact of HIV seropositivity on graft and patient survival after cadaveric renal transplantation in the United States in the pre highly active antiretroviral therapy (HAART) era: an historical cohort analysis of the United States Renal Data System.
BACKGROUND: National statistics are presented for patient survival and graft survival in patients seropositive for the human immunodeficiency virus (HIV+) at the time of renal transplantation in the era prior to highly active antiretroviral therapy (HAART). METHODS: Historical cohort analysis of 63, 210 cadaveric solitary renal transplant recipients with valid HIV serology entries in the United States Renal Data System (USRDS) from 1 January 1987 to 30 June 1997. The medical evidence form was also used for additional variables but, because of fewer available values, was analyzed in a separate model. Outcomes were patient characteristics and survival associated with HIV+ status. RESULTS: Thirty-two patients (0.05%) in the study period were HIV+ at transplant. HIV+ patients were comparable to the national renal transplant population in terms of gender and ethnic distribution but were younger and had younger donors and better HLA matching than the USRDS population. Patient and graft three-year survival were significantly reduced in HIV+ recipients (53% graft, 83% patient survival) relative to the USRDS population (73% and 88%, respectively). In multivariate analysis, HIV+ status was independently associated with patient mortality and decreased graft survival in recipients of cadaveric kidney transplants. CONCLUSIONS: This analysis was retrospective and may underestimate the number of HIV+ patients transplanted in the United States. Although the clinical details of patient selection for transplant were unknown, these results show HIV+ patients can have successful outcomes after cadaveric renal transplantation, although outcomes are significantly different from HIV- recipients.
Adult↗
Use of biosensors to monitor the immune response.
Biosensor instruments, such as the BIACORE, are gaining popularity for analysing serum samples for the presence of antibodies. These instruments offer several advantages in the detection and subsequent characterization of clinically relevant antibodies generated in response to administration of therapeutic proteins. Much like other common immunoassay platforms, immobilized ligand is used to capture antibodies. Unlike conventional approaches, the ligand is immobilized to the surface of a biosensor chip, with detection based upon surface plasmon resonance. This assay platform, therefore, does not require reporter molecules such as enzymes, fluorochromes or radioisotopes that are common to conventional immunoassay methodologies. Additional desirable features of the biosensor platform include real-time detection of the binding of antibody to ligand (for kinetic measurements) as well as straightforward characterization of antibody isotype, specificity and relative concentration. This is all performed with minimum serum requirements (typically 10 microlitres per sample analysed) in a fully automated environment. The unique features of the biosensor instrument warrant that these assays are referred to as biosensor immunoassays to clearly distinguish them from more conventional immunoassay methodologies, such as ELISA.
Antibodies↗
Esophagectomy for esophageal cancer.
This review considers the esophagectomy techniques in the treatment of esophageal cancer and provides the guidelines for optimizing the patients' chances at cure, minimizing the risk of mediastinal enteric leak (which carries a mortality rate as high as 50%) and minimizing associated pulmonary insufficiency and infection. The 4 most commonly used routes for resection and replacement include a transhiatal, transthoracic (Ivor-Lewis), tri-incisional (right chest then simultaneous abdominal and left neck), and left chest (distal tumors). Each of these techniques will be described as will the use of colon and jejunum for esophageal replacement. The healthy stomach is the preferred conduit for esophageal replacement. The stomach is well vascularized, easily reaches to the neck, and requires only a single anastomosis for re-establishing intestinal continuity. When the stomach is not available (usually because of prior surgery or disease) the choice of conduits include colon and jejunum. With respect to minimally invasive esophagectomy for esophageal cancer, several groups have significant experience with this and report excellent results. This is an evolving technique but holds much promise for improving the quality of life of patients with cancer without compromising their survival. In locally advanced middle third tumors, thoracotomy and dissection under direct vision's desirable and improves the safety of the operation. The same may apply to tumors receiving neoadjuvant therapy. For tumors of the distal esophagus, transhiatal, tri-incisional, and Ivor-Lewis resection are probably equally as safe, and appear to result in equivalent long-term survival. An intrathoracic anastomotic leak is disastrous, carrying a mortality rate of up to 50%. Any surgeon who performs esophagectomy with an intrathoracic anastomosis must do so with a low incidence of leakage, certainly under 5%. Consideration should be given to a cervical placement if there are factors increasing the risk such as the use of induction therapy.
Colon↗
Biphasic response of the regional lymphatics in the normal lymphocyte transfer reaction.
BACKGROUND: Initially developed for histocompatibility testing, the normal lymphocyte transfer (NLT) reaction involves the intradermal injection of allogeneic lymphocytes from one individual to another. Because of the unique kinetics of the immunological response to allogeneic lymphocytes, the NLT reaction has been considered an informative system for the analysis of transplant immunity. METHODS: In this study, we used bilateral efferent lymph duct cannulations in sheep to examine the regional lymphatic response to the NLT reaction. Our studies used monoclonal antibodies to define lymphocyte population dynamics and DNA flow cytometry to reflect lymphocyte proliferative responses. RESULTS: The results confirmed a biphasic NLT reaction. An unexpected finding was the marked differences between the early and late NLT responses. The early response was characterized by T-lymphocyte proliferation, as reflected by S-phase DNA, which was comparable in both the NLT-stimulated and contralateral control efferent lymphocytes. This bilateral proliferative response was observed in both CD4+ and CD8+ lymphocytes. In contrast, the late response was restricted to the efferent lymph from the NLT-stimulated lymph node. Dual-parameter flow cytometry demonstrated that the dominant component of this unilateral NLT response was CD8+ lymphocytes. CONCLUSIONS: These results suggest important functional distinctions between systemic and regional lymphatic responses to intradermal alloantigens.
Animals↗
Bronchoscopic volume reduction: a safe and effective alternative to surgical therapy for emphysema.
Lung volume reduction surgery (LVRS), the removal of damaged, hyperexpanded lung, has been shown to improve respiratory function in many patients with end-stage emphysema. We report the results of an animal study using a new transbronchoscopic alternative to LVRS in which a washout solution and fibrin-based glue are used to collapse, seal, and scar target regions of abnormal lung. Twelve sheep had static and dynamic lung functions measured at baseline. Emphysema was produced by inhaled papain (7,000 U/wk x 4 wk), resulting in a significant increase of lung volumes, compliance, and airway resistance. The animals were then divided into three treatment groups of four animals, and underwent surgical volume reduction (SVR), bronchoscopic volume reduction (BVR), or bronchoscopy alone (Sham-BVR). Response to each intervention was assessed 8 to 12 wk after treatment by measuring lung function and examining lung tissue. BVR and SVR groups responded with significant and similar decreases in TLC and residual volume (RV). Tissue examination demonstrated that BVR caused collapse of the lung with focal scarring in 11 of 20 target territories (55% success rate). Three of the 11 target zones developed sterile abscesses. Postprocedure complications were less frequent with BVR than with SVR. This pilot study suggests that lung volume reduction can be achieved in animals without surgery using a bronchoscopic approach and a novel fibrin-based glue system. BVR has the potential for simplifying volume reduction, extending indications, and reducing morbidity, mortality, and costs in humans.
Animals↗
Unusual aspects of breast cancer: case 2. Synchronous bilateral lung and breast cancers.
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Breast Neoplasms↗
Transthoracic esophagectomy with radical mediastinal and abdominal lymph node dissection and cervical esophagogastrostomy for esophageal carcinoma.
BACKGROUND: Several techniques for esophageal resection have been reported. This study examines the morbidity, mortality, and early survival of patients after transthoracic esophagectomy for esophageal carcinoma using current staging techniques and neoadjuvant therapy. The technique includes right thoracotomy, laparotomy, and cervical esophagogastrostomy (total thoracic esophagectomy) with radical mediastinal and abdominal lymph node dissection. METHODS: Three hundred forty-two patients had surgery for esophageal carcinoma between 1989 and 2000 at our institution. Two hundred fifty consecutive patients had esophagectomy using this technique. Kaplan-Meier curves and univariate and multivariate analyses were performed by postsurgical pathologic stage. RESULTS: Median age was 62.7 years (31 to 86 years). Fifty-nine were female. Eighty-one percent (202) had induction chemotherapy (all patients with clinical T3/4 or N1). Early postoperative complications included recurrent laryngeal nerve injury (14% [35]), chylothorax (9%, [22]), and leak (8%, [19]). Median length of stay was 13 days (5 to 330 days). In-hospital or 30-day mortality was 3.6% (9). Overall survival at 3 years was 44%; median survival was 25 months, and 3-year survival by posttreatment pathologic stage was: stage 0 (complete response) (n = 60), 56%; stage I (n = 32), 65%; stage IIA (n = 67), 41%; stage IIB (n = 30), 46%; and stage III (n = 49), 17%. Mean follow-up was 24 months (SEM 1.6, 0 to 138 months). Five patients with tumor in situ, 6 patients with stage IV disease, and 1 patient who could not be staged (12 pts) were excluded from survival and multivariate calculations. In univariate and different models of multivariate analysis, age more than 65 years, posttreatment T3, and nodal involvement were predictive of poor survival. For univariate analysis, p = 0.002, p = 0.004, p = 0.02, respectively; for multivariate analysis, p = 0.001, p = 0.003, p = 0.02, respectively. CONCLUSIONS: Total thoracic esophagectomy with node dissection for esophageal cancer appears to have acceptable morbidity and mortality with encouraging survival results in the setting of neoadjuvant therapy. Patients who show complete response after induction chemoradiotherapy appear to have improved long-term survival.
Abdomen↗
Workshop on bioanalytical methods validation for macromolecules: summary report.
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Biological Assay↗
Memory outcome after left anterior temporal lobectomy in patients with expected and reversed Wada memory asymmetry scores.
PURPOSE: The ideal candidate for anterior temporal lobectomy surgery shows a Wada memory asymmetry (WMA) score characterized by better memory performance in the hemisphere contralateral to the seizure focus relative to the ipsilateral (surgical) hemisphere. However, some surgical candidates show a reversed WMA or better Wada memory performance in the hemisphere of surgical interest relative to the hemisphere contralateral to the seizure focus. To date, no data are available contrasting memory and seizure outcome for these two Wada groups. The present study compared memory and seizure outcome after left anterior temporal lobectomy (L-ATL) in patients showing expected and reversed WMA scores, and also examined the relationship of the individual hemisphere Wada memory scores for predicting verbal memory outcome after L-ATL. METHODS: We compared 6-month postoperative verbal memory change scores and seizure outcome in L-ATL patients with either an expected (n=12) or reversed WMA (n=9) pattern on Wada memory testing. RESULTS: L-ATL patients showing a reversed WMA score had a poorer verbal memory outcome and poorer seizure control after surgery compared with patients showing a WMA score in the expected direction. CONCLUSIONS: L-ATL patients with a reversed WMA score have a greater risk for memory morbidity and poorer seizure outcome than do patients with a WMA score in the expected direction. The WMA score was the best predictor of memory outcome after L-ATL. When the WMA score is not considered, both individual Wada hemisphere scores (contralateral and ipsilateral) provided significant and independent contribution to predicting postoperative verbal memory functioning. These findings are discussed in the context of the functional reserve and hippocampal adequacy models of memory change after temporal lobectomy.
Adult↗
Combined antegrade and retrograde dilation: a new endoscopic technique in the management of complex esophageal obstruction.
BACKGROUND: Esophageal strictures that cause complete obstruction are often difficult to dilate with standard bougienage techniques. METHODS: A new technique was developed and applied, combined antegrade and retrograde dilation, for dilatation of complex esophageal strictures. The stomach is accessed and an endoscope (9.8 mm diameter) is directed under fluoroscopy in a retrograde fashion into the distal esophagus. A guidewire with a hydrophilic coating is advanced through the stricture and then pulled through the mouth with a simultaneously placed proximal endoscope. The guidewire is then used as a guide for antegrade esophageal dilatation. RESULTS: Ten patients with complex esophageal strictures (with and without fistulas) were treated with this technique. Three required a second combined antegrade and retrograde dilation procedure. All strictures were dilated and no perforations occurred. CONCLUSIONS: Combined antegrade and retrograde dilation is a safe and effective technique for dilation of complex obstructing esophageal lesions.
Aged↗
Sequential thoracic metastasectomy prolongs survival by re-establishing local control within the chest.
OBJECTIVE: The value of sequential thoracic metastasectomies is unknown. We evaluate repeat metastasectomy for limited recurrences within the thorax. METHODS: From July 1988 to September 1998, 54 patients underwent 2 to 6 separate sequential procedures to excise metastases after recurrence isolated to the thorax. Kaplan-Meier survival and Cox modeling determined prognostic variables. RESULTS: Thirty-three men and 21 women, 22 to 76 years underwent 2 (100%, n = 54), 3 (50%), 4 (22%), or 5 to 6 (11%) metastasectomies. Fifty-four percent of patients had carcinoma, 35% sarcoma, 9% germ cell, and 2% melanoma. There were no operative deaths; all late deaths occurred from cancer. Median follow-up was 48 months. Cumulative 5-year survival from the second procedure was 57%. After the second, third, fourth, and fifth procedures, respectively, permanent control was achieved in 15 (27%) of 54 patients, 5 (19%) of 27, 1 (8%) of 12, and 0 of 7. Recurrence amenable to additional surgery occurred in 27 (50%) of 54, 12 (44%) of 27, 6 (50%) of 12, and 1 (17%) of 6. Mean hazard for the development of unresectable recurrence increased from 0.21 after the second procedure to 0.91 after the fifth procedure. The 5-year survival for the 27 patients undergoing only 2 metastasectomies was 60% (median not yet reached), 33% for the 15 patients undergoing only 3 metastasectomies (median 34.7 months), and 38% for the 12 patients undergoing 4 or more (median 45.6 months). From the time a recurrence was declared unresectable, patients had a 19% 2-year survival (median 8 months). CONCLUSIONS: Multiple attempts to re-establish intrathoracic control of metastatic disease is justified in carefully selected patients, but the magnitude of benefit decays with each subsequent attempt.
Adult↗
Changes in root cap pH are required for the gravity response of the Arabidopsis root.
Although the columella cells of the root cap have been identified as the site of gravity perception, the cellular events that mediate gravity signaling remain poorly understood. To determine if cytoplasmic and/or wall pH mediates the initial stages of root gravitropism, we combined a novel cell wall pH sensor (a cellulose binding domain peptide-Oregon green conjugate) and a cytoplasmic pH sensor (plants expressing pH-sensitive green fluorescent protein) to monitor pH dynamics throughout the graviresponding Arabidopsis root. The root cap apoplast acidified from pH 5.5 to 4.5 within 2 min of gravistimulation. Concomitantly, cytoplasmic pH increased in columella cells from 7.2 to 7.6 but was unchanged elsewhere in the root. These changes in cap pH preceded detectable tropic growth or growth-related pH changes in the elongation zone cell wall by 10 min. Altering the gravity-related columella cytoplasmic pH shift with caged protons delayed the gravitropic response. Together, these results suggest that alterations in root cap pH likely are involved in the initial events that mediate root gravity perception or signal transduction.
Arabidopsis↗