Citations

Foxp3 expression was initially thought to be restricted to the CD4+CD25+ regulatory T-cell population. However, recent studies suggest that forkhead box P3 (Foxp3) is expressed in CD4+CD25− T cells in aged mice. In the present study in B-cell non-Hodgkin lymphoma (NHL), we found that a subset of intratumoral but not peripheral blood CD4+CD25− T cells, comprising about 15% of intratumoral CD4+ T cells, express Foxp3 and are capable of suppressing the proliferation of autologous infiltrating CD8+ T cells. In vitro activation with OKT3/anti-CD28 antibody (Ab) or dendritic cells (DCs) induced Foxp3 expression in a subset of these CD4+CD25−Foxp3− T cells. We found that the presence of lymphoma B cells during activation augmented activation-induced Foxp3 expression in CD4+CD25− T cells. We also found that CD70+ lymphoma B cells significantly contributed to the activation-induced Foxp3 expression in intratumoral CD4+CD25− T cells. Furthermore, the blockade of CD27-CD70 interaction by anti-CD70 Ab abrogated lymphoma B-cell–mediated induction of Foxp3 expression in intratumoral CD4+CD25− T cells. Taken together, these studies reveal a novel role for NHL B cells in the development of intratumoral regulatory T cells.

Purpose To evaluate the efficacy and safety of ixabepilone in patients with metastatic breast cancer (MBC) resistant to anthracycline, taxane, and capecitabine, in this multicenter, phase II study. Patients and Methods Patients with measurable disease who had tumor progression while receiving prior anthracycline, taxane, and capecitabine were enrolled. Ixabepilone 40 mg/m2 monotherapy was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle. The primary end point was objective response rate (ORR), assessed by an independent radiology facility (IRF). Results A total of 126 patients were treated and 113 were assessable for response. Patients were heavily pretreated: 88% had received at least two lines of prior chemotherapy in the metastatic setting. IRF-assessed ORR was 11.5% (95% CI, 6.3% to 18.9%) for response-assessable patients. Investigator-assessed ORR for all treated patients was 18.3% (95% CI, 11.9% to 26.1%). Fifty percent of patients achieved stable disease (SD); 14.3% achieved SD ≥ 6 months. Median duration of response and progression-free survival were 5.7 and 3.1 months, respectively. Median overall survival was 8.6 months. Patients received a median of 4.0 treatment cycles (range, one to 16 cycles), and 25% of patients received ≥ eight cycles. Grade 3/4 treatment-related events included peripheral sensory neuropathy (14%), fatigue/asthenia (13%), myalgia (8%), and stomatitis/mucositis (6%). Resolution of grade 3/4 peripheral sensory neuropathy occurred after a median period of 5.4 weeks. Conclusion Ixabepilone demonstrated clear activity and a manageable safety profile in patients with MBC resistant to anthracycline, taxane, and capecitabine. Responses were durable and notable in patients who had not previously responded to multiple prior therapies.

The coexistence of urologic malignancy (UM) and abdominal aortic aneurysm (AAA) is rare. Simultaneous treatment may increase morbidity, whereas staged operations delay necessary treatment. We reviewed our experience to develop guidelines for evaluation and management. Clinical data of all patients diagnosed between 1980 and 1998 with both AAA and UM, who also had staged or simultaneous surgical treatment were reviewed. Four thousand forty-seven patients underwent AAA repair during the study period at our institution. Of these, 18 (0.44%) patients, 16 men and two women (mean age: 74 years, range: 61 to 92) had UM. UM was discovered incidentally in nine patients with AAA with computed tomography (CT) scan (7) and ultrasonography (2). In one patient with AAA, hematuria raised the suspicion of UM. Eight patients were diagnosed with AAA during evaluation of UM by CT scan or ultrasound (7) or during laparotomy (1). Initial signs and symptoms included abdominal pain (33%), gross hematuria (33%), and urinary tract infections (17%), although 33% were asymptomatic. The AAA was symptomatic at first examination in three (17%) patients, 14 (78%) patients had hypertension, and two (11%) had renal insufficiency (overall mean serum creatinine: 1.6, range: 0.8 to 3.7). Mean AAA diameter was 5.8 cm (range: 3.8 to 8 cm). Aortography documented significant contralateral renal artery disease in two patients. Twelve patients underwent simultaneous AAA repair and resection of UM; the operations were staged in six (AAA repair first in 2, nephrectomy first in 4). One patient required emergent repair of a ruptured AAA three days after nephrectomy. UM was treated with nephrectomy in 17 patients, and with bilateral ureterectomy and cystectomy in one. A straight aortic graft was implanted in seven patients, a bifurcated graft in ten, and one had extra-anatomic reconstruction. Two patients required reconstruction of the contralateral renal artery. The 30-day mortality rate was 0% after staged and 6% after simultaneous repair (p= >0.1). Major perioperative complications occurred more frequently after simultaneous (42%) than after staged repair (33%), although the difference was not significant (p= >0.1). Two patients developed postoperative renal failure. Seventeen patients were followed for an average of 3.9 years (14 days to 10.8 years). Three (17%) patients died of recurrent cancer at 1, 10.7, and 10.8 years after surgery. Patients with resectable UM have satisfactory long-term survival, which justifies aggressive treatment of concomitant AAA. Aortography in these patients is suggested to exclude contralateral renal artery disease. Complications were frequent, but simultaneous repair did not increase morbidity or mortality significantly. The risk of AAA rupture after nephrectomy, need to correct contralateral renal artery disease at the time of nephrectomy, and disadvantage of delaying treatment of UM are compelling reasons to favor simultaneous treatment of AAA and UM.

The purpose of this study was to examine the technical aspects of intraoperative duplex ultrasound (DUS) following carotid endarterectomy (CEA), suggest criteria to differentiate significant lesions requiring immediate surgical revision from normal or benign defects, and evaluate how frequently intraoperative DUS provides useful or unsuspected information. A retrospective study was performed on all patients who had both CEA and intraoperative carotid DUS between January 1,1990. and January 1,1995. A total of 155 DUS examinations were performed in 149 patients. Findings were grouped into three categories: normal; minor/insignificant lesions; and hemodynamically significant lesions based on the presence or absence of elevated peak systolic velocities, visible stenosis/thrombus, or intimal flap/dissection. Postoperative status was correlated with intraoperative DUS findings. Ninety-one (59%) examinations performed on 87 patients produced normal findings. Forty-seven (30%) examinations performed on 45 patients showed minor abnormalities consisting of insignificant residual plaque, residual external carotid artery stenoses, small intimal flaps, elevated velocities with no associated anatomic lesion, or an arterial kink. Fourteen patients (9%) had significant findings requiring immediate surgical revision. These consisted of large intimal flaps or dissection in six patients, marked residual plaque and significant stenosis in five patients, thrombus in two patients, and a kink in one patient. Three additional patients ( 2 %) had significant findings but were not revised for various reasons. No significant difference was identified in morbidity or mortality rates between those patients with normal findings, those patients with minor technical defects, and those patients with significant abnormalities undergoing immediate surgical revision. However, two of three patients who had significant abnormalities within the common carotid artery that were not revised suffered perioperative ipsilateral strokes. Intraoperative DUS is a safe and accurate method to assess the technical adequacy of CEA. Intraoperative DUS showed significant lesions in 11% of patients. Identification and immediate repair of significant technical defects may decrease perioperative complication rate and long-term restenosis rate.

Abstract The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed.

We evaluated injury patterns at two wrestling tourna ments involving 1742 participants, aged 6 to 16 years. The overall injury rate was 12.7%. Injuries requiring withdrawal from the tournament occurred in 4.6% of the participants. Of all participants, 3% sustained an injury in their first match, and 1.1 % sustained an injury during their first match that required withdrawal from the tournament. Primary areas of injury were the upper extremity (33%) and the neck and back (24%). Wil coxon rank-sum tests revealed that increasing age and increasing weight were correlated with injury, whereas multiple logistic regression analysis revealed that only increasing age was correlated with injury. These find ings suggest the need for medical supervision at large wrestling tournaments, where it is likely that severe injuries will occur. In addition, older wrestlers and per haps heavier wrestlers are at an increased risk for injury.

Golf is an activity generally stressful to the hands and wrists and particularly can produce increasing symp toms in players with underlying problems such as hand and wrist arthritis or tendinitis. The purpose of this study was to quantitate wrist motion and club head/ ball impact force in subjects with pathologic conditions of the hand, wrist, or forearm, within a laboratory environment. A regular straight-handled golf club was compared to a new BioCurve handle design that has a 19° ulnar bend. We measured and compared the effect of the two grips on wrist motion, club head velocity, ball impact force, ball impact location, and isometric torsional strength in 20 subjects who had a variety of upper extremity disorders. This data was then com pared to data collected in an identical fashion from golfers without such conditions. The results of our study show that there were no differences related to club handle design on impact force or impact location, club head velocity, or club head path and face angle. Wrist kinematic differences were minimal between handle designs. The differences that were significant (P < 0.05) centered around the decreased ulnar deviation of the left hand that resulted when subjects used the BioCurve handle design, which also allowed greater resistance to torque than the straight grip club. In addition to collecting objective data, we asked subjects for their opinions of the two grips. As a whole, the normal group and the group with pathologic conditions noted more comfort, improved grip, and less shock transmission with the BioCurve handle.

The purpose of this study was to investigate the rela tionship of isometric and isokinetic endurance of the forearm complex under maximum effort in a healthy population. Isometric and isokinetic endurance meas urements of elbow flexion and extension of the domi nant and nondominant sides were made in 32 healthy male subjects (age range, 21 to 39 years). Both fatigue rates and the amount of time elapsed in reaching fatigue were determined. Analysis of these data reveals that 1) isometric endurance of the forearm complex cannot be used as a predictor of isokinetic endurance, as there is no relationship between the two, 2) dominant and non dominant endurance are related, a result that supports the belief that in the assessment of the endurance of a single diseased upper extremity, the best available comparison is with the contralateral healthy extremity, and 3) healthy males in the age range tested have greater endurance in elbow extension than in flexion.