Use of multiple T cell-directed intact ricin immunotoxins for autologous bone marrow transplantation

The monoclonal antibodies (MoAb) T101, G3.7, 35.1, and TA-1 were conjugated to intact ricin using a thioether linkage. These MoAb detect, respectively, the CD5[gp67], CD7[p41], CD2[p50], and [gp95, 170] determinants that are found in the vast majority of cases of T cell acute lymphocytic leukemia (T-ALL). The resulting immunotoxins (ITs) and an equimolar mixture of these ITs were evaluated as potential purgative reagents for autologous transplantation in T-ALL. Leukemic cell lines were used to compare the kinetics of protein synthesis inactivation mediated by each IT. The cells were treated with IT in the presence of lactose in order to block the native binding of ricin. The observed rates of protein synthesis inactivation correlated with target antigen expression detected by fluorescence-activated cell sorter analysis. Of the four ITs, T101-ricin (T101-R) exhibited the fastest rate of inactivation, followed in order by G3.7-ricin, TA-1-ricin, and 35.1-ricin. At concentrations greater than 300 ng/mL, a cocktail containing an equimolar amount of all four ITs (referred to as the four- IT cocktail) exhibited kinetics that were as fast or faster than those of T101-R. The long-term cytotoxic effects of individual ITs and the four-IT cocktail were evaluated using a sensitive clonogenic assay. Each IT was specifically cytotoxic and inhibited 1 to 4 logs of clonogenic leukemic cells at doses (300 to 600 ng/mL) that can be used clinically. The four-IT cocktail was highly cytotoxic; a concentration of 300 ng/mL inhibited greater than 4 logs of leukemic cells while sparing the majority of committed (CFU-GM, CFU-E) and pluripotent (CFU- GEMM) hematopoietic stem cells. The determination of both short-term kinetics of protein synthesis inactivation and longer-term inhibition of clonogenic growth allowed new insight into cell killing by IT. Our results suggest that ITs continue to act on clonogenic target cells for a period of three to five days. Interestingly, the four-IT cocktail was not as potent against clonogenic leukemic cells as T101-R alone, although it exhibited kinetics of protein synthesis inhibition that were as fast as those of T101-R alone. This finding suggests that internalized ITs may differ in the length of time they remain active within the cell. Our results also demonstrate the importance of using several different assays to evaluate IT reagents.     

Serial electrophysiologic studies of the effects of oral diltiazem on paroxysmal supraventricular tachycardia

In 16 patients with paroxysmal supraventricular tachycardia, electrophysiologic studies were done before and serially at hourly intervals for eight hours after the third oral dose of 90 mg diltiazem given every eight hours. Diltiazem increased both the longest atrial paced cycle length producing type 1 atrioventricular block and the effective refractory period of the atrioventricular conducting system at all measurements. Before diltiazem, all 16 patients had induction of sustained tachycardia. After diltiazem, sustained tachycardia could not be induced in ten patients at any measurements; in these patients, either echo or nonsustained tachycardia was induced. In the remaining six patients, sustained tachycardia was induced, particularly after six hours. Follow-up observations in 12 patients receiving the same dosage of oral diltiazem for 6 +/- 2 months (mean +/- SD), showed that of the eight patients in whom electrophysiologic testing induced either echo or nonsustained tachycardia, six were asymptomatic and two experienced transient palpitation. Of the other four patients with induction of sustained tachycardia, three had transient palpitation and one had occasional attacks of sustained tachycardia requiring modification of therapy. Thus, oral diltiazem increases atrioventricular nodal refractoriness, with an effect lasting up to eight hours. It is an effective agent for the prophylaxis of paroxysmal supraventricular tachycardia.     

A logistic regression analysis of multiple noninvasive tests for the prediction of the presence and extent of coronary artery disease in men

The incremental diagnostic yield of clinical data, exercise ECG, stress thallium scintigraphy, and cardiac fluoroscopy to predict coronary and multivessel disease was assessed in 171 symptomatic men by means of multiple logistic regression analyses. When clinical variables alone were analyzed, chest pain type and age were predictive of coronary disease, whereas chest pain type, age, a family history of premature coronary disease before age 55 years, and abnormal ST-T wave changes on the rest ECG were predictive of multivessel disease. The percentage of patients correctly classified by cardiac fluoroscopy (presence or absence of coronary artery calcification), exercise ECG, and thallium scintigraphy was 9%, 25%, and 50%, respectively, greater than for clinical variables, when the presence or absence of coronary disease was the outcome, and 13%, 25%, and 29%, respectively, when multivessel disease was studied; 5% of patients were misclassified. When the 37 clinical and noninvasive test variables were analyzed jointly, the most significant variable predictive of coronary disease was an abnormal thallium scan and for multivessel disease, the amount of exercise performed. The data from this study provide a quantitative model and confirm previous reports that optimal diagnostic efficacy is obtained when noninvasive tests are ordered sequentially. In symptomatic men, cardiac fluoroscopy is a relatively ineffective test when compared to exercise ECG and thallium scintigraphy.     

The Application of Transcranial Doppler Sonography in Patients with Chronic Subdural Haematoma

Summary  The aim of this study was to evaluate the haemodynamic changes of the middle cerebral artery (MCA) and their clinical significance before and after surgical aspiration in patients with chronic subdural haematoma (CSDH).  Nineteen patients with CSDH (17 unilateral and 2 bilateral) received transcranial Doppler sonography (TCD) examinations for cerebral blood flow velocity (CBFv) of the MCA prior to and 5 days after neurosurgical treatment. A total of 21 lesion and 10 non-lesion hemispheres were included. Cranial computerized tomography (CT) and clinical assessments were performed before and 3 months following surgery.  The preoperative TCD study revealed that the lesion hemisphere had a modest decrease in CBFv in the MCA as compared to the non-lesion hemisphere. Postoperatively, the CBFv significantly improved in the lesion hemisphere, but not in the non-lesion hemisphere, compared to the preoperative data (P<0.005). The improvement in CBFv showed no significant correlation with brain shift and haematoma volume of the initial cranial CT. Additionally, two patients, who were proved to have a postoperative complication of subdural pneumocephalus, failed to attend follow-up examinations of TCD.  Our results support TCD as an alternative follow-up examination for patients with CSDH, although it may not be sensitive enough as a preoperative screening tool. Postoperatively, improvements in the CBFv of the lesion hemisphere are characteristic. An unexplained difficulty of accessing cerebral basal arteries in follow-up TCD examinations should suggest pneumocephalus in the primary differential diagnosis.     

Altered Serum Transforming Growth Factor-ß1 and Monocyte Chemoattractant Protein-1 Levels in Obstructive Jaundice

Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-ß1 (TGFß1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFß1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFß1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFß1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFß1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFß1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.     

Alterations of bone geometry, density, microarchitecture, and biomechanical properties in systemic lupus erythematosus on long-term glucocorticoid: a case–control study using HR-pQCT

Summary

Compared to controls, HR-pQCT at distal radius of SLE patients on chronic glucocorticoid (SLE/GC) revealed reduced bone area, vBMD, deteriorated microarchitecture, and unevenly distributed stresses limited to cortical bone. Despite similar trabecular quality, whole bone strength decreased in patients. These alterations may partly explain high fracture rates in SLE/GC.

Introduction

To assess bone geometric, densitometric, microarchitectural, and biomechanical properties in patients with systemic lupus erythematosus (SLE) on long-term glucocorticoid (GC) (SLE/GC) as compared with healthy controls.

Methods

A total of 180 female SLE patients and 180 healthy controls were in this cross-sectional study to assess areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) and microfinite element analysis (μFEA) was performed at distal radius.

Results

In addition to significantly lower aBMD at femoral neck, total hip and lumbar spine, cortical area, average volumetric BMD (vBMD) and cortical vBMD also significantly reduced by 5.3, 5.7, to 1.9 % in SLE patients, respectively. Deteriorations of cortical microarchitecture were pronounced in patients, with 6.3 % reduction in cortical thickness and 13.6 % higher in cortical porosity. Local stresses were more unevenly distributed through cortical bone in patients. SLE/GC patients had decreased whole bone stiffness, estimated failure load, and apparent modulus. Parameters related to trabecular bone density and microarchitecture were comparable between patients and controls.

Conclusion

In SLE/GC patients, despite a reduction in bone area, vBMD and deteriorated microarchitecture and unevenly distributed stresses limited to the cortical compartment, whole bone strength decreased. HR-pQCT and μFEA were promising in elucidating the potential underlying pathophysiology of bone loss and propensity to fracture in SLE/GC and provide us additional information about alterations of bone quality which might better predict fracture risk beyond aBMD in SLE/GC.     

Ultrasound for the detection of vegetative foreign body in hand--a case report.

Foreign bodies in soft tissues are commonly encountered in daily orthopaedic practice. While most of the metals and glass foreign bodies can be detected by plain radiograph, organic substances such as wood and vegetative materials are radiolucent. Unfortunately, these radiolucent foreign bodies are usually more prone to cause an inflammatory reaction and infection. The detection can be even more difficult in cases of multiple foreign bodies and in penetrating injuries with small innocuous skin wounds. Ultrasonography is a sensitive and reliable investigation for detection of foreign bodies in soft tissue. We present a case of penetration injury to thumb with residual radiolucent foreign bodies and demonstrate the proper role of ultrasonography in the management of foreign bodies in soft tissues.     

Laryngeal mask airway in patients with tracheal stents who are undergoing non-airway related interventions: report of three cases

The tracheal stent is an alternative nonsurgical management tool for patients with tracheal stenosis caused by disease or iatrogenic trauma. Some patients with tracheal stent may need to be anesthetized to allow invasive techniques or surgery to be performed. In these patients, general anesthesia by endotracheal intubation may dislodge the stent distally or cause lethal complications such as bleeding. We describe three patients with a tracheal stent in place, who were anesthetized using a Laryngeal Mask Airway for surgery, with smooth results.     

Arthroscopic repair of Bankart lesion in traumatic anterior-inferior shoulder instability using the two-portal method: A preliminary report

BackgroundIn this report, we describe our preliminary clinical results of arthroscopic Bankart repair in traumatic anterior-inferior shoulder instability using the two-portal method.MethodFrom August 2009 to December 2011, arthroscopic repair of Bankart lesion using this method was performed in 16 consecutive patients who were prospectively enrolled. Fifteen shoulders were treated with two-anchor sutures and one was treated with three-anchor sutures. Twelve patients received metallic anchor screws and four patients received bioanchor screws. The assessments were performed using the Rowe score, the University of California at Los Angeles shoulder rating scale, the American Shoulder and Elbow Surgeons score, and the shoulder range of motion (ROM) deficit.ResultsWith an average follow-up period of 22.9 months, all shoulder scores improved after surgery (p < 0.001). The average ROM deficit of the operated shoulders was not significant as compared with the healthy side in forward elevation (p > 0.05), but was significant in external rotation (p < 0.05). All of the 16 shoulders remained stable (100%) after the arthroscopic repair surgery. All patients returned to their preinjury levels of daily activity without recurrent problems.ConclusionIn patients with traumatic anterior glenohumeral instability, arthroscopic Bankart repair with the two portal method can provide good results. It can be an alternative method of treating patients with Bankart lesion without associated major glenoid defect or rotator cuff lesion in traumatic anterior-inferior instability.