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1.
Phys Rev Lett ; 120(10): 100401, 2018 Mar 09.
Article in English | MEDLINE | ID: mdl-29570331

ABSTRACT

We investigate dynamical three-body correlations in the Bose gas during the earliest stages of evolution after a quench to the unitary regime. The development of few-body correlations is theoretically observed by determining the two- and three-body contacts. We find that the growth of three-body correlations is gradual compared to two-body correlations. The three-body contact oscillates coherently, and we identify this as a signature of Efimov trimers. We show that the growth of three-body correlations depends nontrivially on parameters derived from both the density and Efimov physics. These results demonstrate the violation of scaling invariance of unitary bosonic systems via the appearance of log-periodic modulation of three-body correlations.

2.
Br J Cancer ; 110(10): 2479-88, 2014 May 13.
Article in English | MEDLINE | ID: mdl-24762959

ABSTRACT

BACKGROUND: Mesothelioma is a notoriously chemotherapy-resistant neoplasm, as is evident in the dismal overall survival for patients with those of asbestos-associated disease. We previously demonstrated co-activation of multiple receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR), MET, and AXL in mesothelioma cell lines, suggesting that these kinases could serve as novel therapeutic targets. Although clinical trials have not shown activity for EGFR inhibitors in mesothelioma, concurrent inhibition of various activated RTKs has pro-apoptotic and anti-proliferative effects in mesothelioma cell lines. Thus, we hypothesised that a coordinated network of multi-RTK activation contributes to mesothelioma tumorigenesis. METHODS: Activation of PI3K/AKT/mTOR, Raf/MAPK, and co-activation of RTKs were evaluated in mesotheliomas. Effects of RTK and downstream inhibitors/shRNAs were assessed by measuring mesothelioma cell viability/growth, apoptosis, activation of signalling intermediates, expression of cell-cycle checkpoints, and cell-cycle alterations. RESULTS: We demonstrate activation of the PI3K/AKT/p70S6K and RAF/MEK/MAPK pathways in mesothelioma, but not in non-neoplastic mesothelial cells. The AKT activation, but not MAPK activation, was dependent on coordinated activation of RTKs EGFR, MET, and AXL. In addition, PI3K/AKT/mTOR pathway inhibition recapitulated the anti-proliferative effects of concurrent inhibition of EGFR, MET, and AXL. Dual targeting of PI3K/mTOR by BEZ235 or a combination of RAD001 and AKT knockdown had a greater effect on mesothelioma proliferation and viability than inhibition of individual activated RTKs or downstream signalling intermediates. Inhibition of PI3K/AKT was also associated with MDM2-p53 cell-cycle regulation. CONCLUSIONS: These findings show that PI3K/AKT/mTOR is a crucial survival pathway downstream of multiple activated RTKs in mesothelioma, underscoring that PI3K/mTOR is a compelling target for therapeutic intervention.


Subject(s)
Antineoplastic Agents/pharmacology , Mesothelioma/enzymology , Neoplasm Proteins/antagonists & inhibitors , Phosphoinositide-3 Kinase Inhibitors , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/antagonists & inhibitors , Butadienes/pharmacology , Cell Cycle/drug effects , Cell Line, Tumor , Chromones/pharmacology , Drug Screening Assays, Antitumor , Enzyme Activation/drug effects , Everolimus , Humans , Imidazoles/pharmacology , Indazoles/pharmacology , MAP Kinase Signaling System , Mesothelioma/pathology , Molecular Targeted Therapy , Morpholines/pharmacology , Neoplasm Proteins/physiology , Nitriles/pharmacology , Phosphatidylinositol 3-Kinases/physiology , Quinolines/pharmacology , RNA Interference , RNA, Small Interfering/pharmacology , Receptor Protein-Tyrosine Kinases/physiology , Sirolimus/analogs & derivatives , Sirolimus/pharmacology , Sulfonamides/pharmacology , TOR Serine-Threonine Kinases/physiology , raf Kinases/physiology
3.
Vox Sang ; 104(4): 324-30, 2013 May.
Article in English | MEDLINE | ID: mdl-23384253

ABSTRACT

BACKGROUND AND OBJECTIVES: The purpose of our studies was to determine the effects of extended platelet storage on poststorage platelet viability. MATERIALS AND METHODS: Normal subjects were recruited to donate platelets using two different apheresis systems: either the COBE Spectra (n = 58) or the Haemonetics MCS+ (n = 84). Platelet recovery and survival data from the two systems were compared with each other and with in vitro measurements of the stored platelets. RESULTS: There were no significant differences in either platelet recoveries or survivals between the two machines between 1 and 8 days of storage. Combining the data from both machines, platelet recoveries decreased by 2.6% and survivals by 0.3 days/storage day. In vitro assays did not predict either platelet recoveries or survivals during storage for 5-8 days. After 9 days of storage, pHs were unacceptable (≤ 6.1), suggesting that 8 days will be the longest possible storage time. CONCLUSIONS: These data suggest that, if stored platelet bacterial contamination issues are resolved, significant extension of platelet storage times is possible.


Subject(s)
Blood Platelets/cytology , Blood Preservation/methods , Plateletpheresis/methods , Cell Survival/physiology , Humans , Retrospective Studies , Time Factors
4.
Oncogene ; 30(14): 1643-52, 2011 Apr 07.
Article in English | MEDLINE | ID: mdl-21132014

ABSTRACT

Mesothelioma is an asbestos-associated and notoriously chemotherapy-resistant neoplasm. Activation of the receptor tyrosine kinases (RTKs), epidermal growth factor receptor and MET, has been described in subsets of mesothelioma, suggesting that TKs might represent therapeutic targets in this highly lethal disease. We employed proteomic screening by phosphotyrosine immunoaffinity purification and tandem mass spectrometry to characterize RTK activation in mesothelioma cell lines. These assays demonstrated expression and activation of the AXL protein, which is an RTK with known oncogenic properties in non-mesothelial cancer types. AXL was expressed and activated strongly in 8 of 9 mesothelioma cell lines and 6 of 12 mesothelioma biopsies, including each of 12 mesotheliomas with spindle-cell histology. Somatic AXL mutations were not found, but all mesotheliomas expressed an alternatively spliced AXL transcript with in-frame deletion of exon 10, and six of seven mesothelioma cell lines expressed the AXL ligand, growth arrest-specific 6 (GAS6). GAS6 expression appeared to be functionally relevant, as indicated by modulation of AXL tyrosine phosphorylation by knockdown of endogeneous GAS6, and by administration of exogenous GAS6. AXL silencing by lentivirus-mediated short hairpin RNA suppressed mesothelioma migration and cellular proliferation due to G1 arrest. The AXL inhibitor DP-3975 inhibited cell migration and proliferation in mesotheliomas with strong AXL activation. DP-3975 response in these tumors was characterized by inhibition of PI3-K/AKT/mTOR and RAF/MAPK signaling. AXL inhibition suppressed mesothelioma anchorage-independent growth, with reduction in colony numbers and size. These studies suggest that AXL inhibitors warrant clinical evaluation in mesothelioma.


Subject(s)
Cell Proliferation/drug effects , Mesothelioma/genetics , Pleural Neoplasms/genetics , Proto-Oncogene Proteins/genetics , Receptor Protein-Tyrosine Kinases/genetics , Alternative Splicing , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/genetics , Exons , Gene Silencing , Humans , Intercellular Signaling Peptides and Proteins/isolation & purification , Mesothelioma/drug therapy , Mesothelioma/pathology , Neoplasm Invasiveness/genetics , Phosphorylation , Pleural Neoplasms/drug therapy , Pleural Neoplasms/pathology , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/metabolism , Sequence Deletion , Signal Transduction/drug effects , Signal Transduction/genetics , Axl Receptor Tyrosine Kinase
5.
Neuroscience ; 163(3): 920-32, 2009 Oct 20.
Article in English | MEDLINE | ID: mdl-19596055

ABSTRACT

Activity-dependent modulation of N-methyl-d-aspartate (NMDA) receptors containing selective NR2 subunits has been implicated in plastic processes in developing and adult sensory cortex. Aiming to reveal differential sensitivity of NR2 subunits to sustained changes in sensory activity, we utilized four paradigms that blocked, reinstated, or initiated sensory visual activity. Laminar prevalence of N-methyl-d-aspartate receptor subunit 2A- (NR2A)- and N-methyl-d-aspartate receptor subunit 2B- (NR2B)-containing synapses in visual cortex of postnatal and adult ferrets was assessed using quantitative electron microscopy. Light-deprivation at all ages resulted in a downregulation of NR2A, while recovery from deprivation resulted in an upregulation. Furthermore, premature eyelid opening caused a precocious increase of NR2A. Thus, transitions between periods of dark and light rapidly and bidirectionally regulate NR2A, regardless of cortical layer or age. In contrast, NR2B regulation is layer- and age-dependent. Only in layer IV, NR2B prevalence displays a one-time decline about 3 weeks after the initiation of sensory activity upon normal or premature eyelid opening, or upon termination of dark-rearing. Incongruity in patterns of NR2A and NR2B modulation by activity is consistent with involvement of these subunits in two distinct, yet partially co-occurring processes: developmental plasticity with a critical period, and lifelong plasticity that is established in early developmental ages.


Subject(s)
Receptors, N-Methyl-D-Aspartate/biosynthesis , Visual Cortex/metabolism , Age Factors , Animals , Animals, Newborn , Darkness , Down-Regulation , Ferrets , Light , Neuronal Plasticity , Photic Stimulation , Protein Subunits/biosynthesis , Synapses/metabolism , Up-Regulation
6.
Colorectal Dis ; 4(4): 240-245, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12780593

ABSTRACT

OBJECTIVE: Untreated malignant large bowel obstruction is rapidly fatal. Short-term palliation of symptoms can be achieved by formation of a stoma in those patients for whom resection surgery is inappropriate. In the final months of life, a stoma represents a significant burden for both patients and carers. Palliative endoluminal stenting may therefore be an attractive alternative option for this poor prognosis group. In this paper, we examine our experience of palliative endoluminal colonic stenting. PATIENTS: Twenty patients, 11 males and 9 females of median age 81 years were referred for stenting. All had left sided colonic cancers. Ten patients had confirmed metastases on presentation, four had fixed rectal cancers and the remainder had severe comorbidity limiting surgical options. Stents were placed endoscopically using a radiologically controlled 'stent over wire' technique. RESULTS: Stenting successfully relieved the obstruction in 18 of the 20 patients attempted. In one patient the stricture could not be negotiated and the procedure was abandoned. Eleven patients have died of their disease, their median duration of palliation was 50 days (3-152 days). The rest of the patients continue in follow-up and have had 80 days median palliation (14-257 days). One stent-related complication has been observed in a patient who suffered anal pain due to fracture and migration of part of a stent into the low rectum. This complication occurred after 250 days and the distal stent fragment was removed with further symptom relief. CONCLUSION: Carefully selected patients benefit from colonic endoluminal stenting with relief of obstructive symptoms. They may be spared the potential problems associated with palliative stoma formation.

7.
Vasc Surg ; 35(5): 415-8, 2001.
Article in English | MEDLINE | ID: mdl-11565048

ABSTRACT

The management of acute mesenteric ischemia in the contaminated abdomen may require the use of an autogenous graft to achieve mesenteric revascularization. The authors present a case of an ischemic small bowel perforation in a 62-year-old-woman whose preoperative angiogram demonstrated occlusion of the celiac, superior mesenteric, and inferior mesenteric arteries. Vein mapping of the right greater saphenous vein demonstrated a dual saphenous system whose individual diameters were more than 4 millimeters. Exploratory laparotomy revealed a diffusely ischemic small bowel and liver, as well as abdominal sepsis from the perforated small bowel. Revascularization was accomplished by using saphenous vein in a nonreversed orientation as a bifurcated conduit from the supraceliac aorta to the hepatic and superior mesenteric arteries. Following revascularization, the liver and small bowel immediately regained a normal perfused appearance and the perforated segment of small bowel was resected and reanastomosed. She returned for a follow-up clinic visit 5 months later and was found to have an asymptomatic 6 cm aneurysm involving the proximal mesenteric vein bypass. The aneurysmal aspect of the vein bypass was replaced with a polytetrafluoroethylene interposition graft originating from the supraceliac aorta. On follow-up 3 months later, her aortomesenteric bypass is patent without aneurysmal recurrence, and she is clinically asymptomatic from any symptoms of mesenteric ischemia.


Subject(s)
Abdomen/microbiology , Abdomen/surgery , Mesenteric Artery, Inferior/surgery , Mesenteric Artery, Superior/surgery , Vascular Surgical Procedures , Female , Humans , Intestine, Small/injuries , Intestine, Small/surgery , Middle Aged , Rupture/surgery
8.
Ann Vasc Surg ; 15(1): 32-6, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11221941

ABSTRACT

The purpose of this study was to review the long-term outcomes, particularly patient satisfaction, of patients surgically treated for thoracic outlet syndrome (TOS). All patients who had undergone surgery for TOS at the University of Iowa Hospitals and Clinics between 1988 and 1999 were reviewed. A retrospective chart review of 29 patients (36 operations) was performed. In addition, 20 (69%) of the patients were able to be contacted for a phone survey. There was no operative mortality. Specific neurologic complications occurred in 4/36 operations (11%) including one brachial plexus traction palsy, two phrenic nerve palsies, and one long thoracic nerve palsy. All nerve palsies were either mild or temporary. Mean follow-up was 4 years. On phone survey, 80% of the patients were actively employed. Twenty-seven percent reported that they had an excellent result, 58% reported they had a good result, 8% reported that they had a fair result, and 8% had a poor result. If they had it to do over again, 85% of the patients would have the same surgery again for relief of TOS.


Subject(s)
Patient Satisfaction , Thoracic Outlet Syndrome/surgery , Adult , Employment , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Thoracic Outlet Syndrome/etiology
9.
Ann Vasc Surg ; 14(6): 679-82, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11128468

ABSTRACT

Outflow obstruction in patients with hemodialysis access can cause venous hypertension and jeopardize the patency of the access site. Numerous surgical procedures have been described to decompress an occluded subclavian vein. In this report, we describe the use of the contralateral internal jugular vein as a bypass conduit to decompress an occluded brachiocephalic vein in a patient whose dialysis was dependent on this vein access.


Subject(s)
Arteriovenous Fistula , Graft Occlusion, Vascular/surgery , Jugular Veins/transplantation , Renal Dialysis , Adult , Anastomosis, Surgical , Brachiocephalic Trunk/diagnostic imaging , Brachiocephalic Trunk/surgery , Graft Occlusion, Vascular/diagnostic imaging , Humans , Male , Phlebography , Reoperation
10.
Phys Rev Lett ; 85(23): 4932-5, 2000 Dec 04.
Article in English | MEDLINE | ID: mdl-11102154

ABSTRACT

We combine the results of terahertz time-domain spectroscopy with far-infrared transmission and reflectivity to obtain the conductivity of SrRuO3 over an unprecedented continuous range in frequency, allowing us to characterize the approach to zero frequency as a function of temperature. We show that the conductivity follows a simple phenomenological form, with an analytic structure fundamentally different from that predicted by the standard theory of metals.

11.
Am J Surg Pathol ; 24(9): 1183-200, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10976692

ABSTRACT

The separation of benign from malignant mesothelial proliferations has emerged as a major problem in the pathology of the serosal membranes. For both epithelial and spindle cell mesothelial processes, true stromal invasion is the most accurate indicator of malignancy, but stromal invasion is often difficult to assess, especially in small biopsies. In the pleural cavity, deep penetration of a thickened and fibrotic pleura or penetration of mesothelial cells into the fat of the chest wall are good indicators of malignancy; however, superficial entrapment of mesothelial cells and glands by organizing effusions is common in benign reactions and needs to be distinguished from invasion. In the peritoneal cavity, invasion of fat or of organ walls is again the most reliable indicator of malignancy, but entrapment of benign cells in organizing granulation tissue or between fat lobules is frequent and confusing. Proliferations confined to the pleural or peritoneal space, particularly linear arrays of atypical mesothelial cells on the free surface, should not be called malignant in the absence of unequivocal invasion. Cytologic atypia is often not helpful in separating benign from malignant reactions, because benign processes are commonly atypical and mesotheliomas are often deceptively monotonous. Densely packed mesothelial cells within the pleural space are frequent in benign reactions, but densely packed mesothelial cells within the stroma favor a diagnosis of malignancy. Organizing effusions (fibrous pleurisy) typically show zonation with high cellularity and cytologic atypia toward the pleural space and increasing fibrosis with decreasing cellularity and lesser atypia toward the chest wall, whereas sarcomatous (including desmoplastic) mesotheliomas do not demonstrate this type of zonation. Elongated capillaries perpendicular to the pleural surface are seen in organizing effusions but are not a feature of sarcomatous mesotheliomas. The combination of a paucicellular storiform pattern, plus invasion of the stroma (including fat and adjacent tissues), or bland necrosis, overtly sarcomatous foci, or distant metastases, is required for the diagnosis of desmoplastic mesothelioma. Necrosis is usually a sign of malignancy but is occasionally seen in benign mesothelial reactions. Keratin staining is useful in indicating the distribution of mesothelial cells, and particularly in demonstrating penetration of mesothelial cells into the stroma or adjacent structures, but is of no help in separating benign and malignant proliferations because both are keratin-positive. Although both p53 and EMA staining have been proposed as markers of mesothelial malignancy, in our experience they are not helpful for the individual case.


Subject(s)
Epithelial Cells/pathology , Mesothelioma/pathology , Diagnosis, Differential , Epithelium/pathology , Humans , Peritoneal Neoplasms/pathology , Peritoneum/pathology , Pleura/pathology , Pleural Neoplasms/pathology , Pleurisy/pathology
12.
Phys Rev Lett ; 85(12): 2569-72, 2000 Sep 18.
Article in English | MEDLINE | ID: mdl-10978109

ABSTRACT

We have measured the complex conductivity sigma of a Bi(2)Sr(2)CaCu(2)O(8+delta) thin film between 0.2 and 0.8 THz. We find sigma in the superconducting state to be well described as the sum of contributions from quasiparticles, condensate, and order parameter fluctuations which draw 30% of the spectral weight from the condensate. An analysis based on this decomposition yields a quasiparticle scattering rate on the order of k(B)T/Planck's over 2pi for temperatures below T(c).

13.
BMJ ; 320(7247): 1471; author reply 1473-4, 2000 May 27.
Article in English | MEDLINE | ID: mdl-10877562
14.
Parasite Immunol ; 22(6): 297-305, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10849309

ABSTRACT

Parasite-induced immunosuppression is believed to play a significant role in the pathology of cysticercosis, a disease caused by the larval stage of cestode parasites. The biochemical basis for immunoregulation by Taenia crassiceps in experimental cysicercosis is unknown. In order to determine whether or not excretory/secretory (E/S) products from the parasite have the ability to regulate host immune function, the activity of these products was examined. Excretory/secretory products from larvae early in the infection were found to suppress T cell proliferative responses in vitro as well as the production of IFN-gamma and IL-4. In contrast, E/S products secreted from larvae harvested late in infection were not suppressive. Electrophoretic analysis of E/S products revealed both qualitative and quantitative differences in the pattern of proteins produced by larvae taken from an early infection versus those taken from a chronic infection. The viability of parasites taken from an early infection was greatly reduced compared to those taken from chronically infected mice, suggesting a change in the nature of the host immune response to the parasite during the course of the infection. The proliferative activity and cytokine profiles of host immune cells were examined. Both mesenteric lymph node cells and peritoneal exudate cells were found to produce high levels of both IFN-gamma and IL-4, consistent with the high levels of these cytokines in sera of chronically infected animals. Chronic infection with Taenia crassiceps therefore is characterized by high levels of production of both Th1 and Th2 cytokines by host cells.


Subject(s)
Cysticercosis/immunology , Taenia/pathogenicity , Age Factors , Animals , Ascitic Fluid/cytology , Ascitic Fluid/immunology , Cell Division/drug effects , Concanavalin A , Cysticercosis/parasitology , Down-Regulation , Electrophoresis, Polyacrylamide Gel , Female , Helminth Proteins/analysis , Helminth Proteins/pharmacology , Interferon-gamma/analysis , Interleukin-4/analysis , Larva/immunology , Lymph Nodes/immunology , Mesentery , Mice , Mice, Inbred BALB C , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Taenia/growth & development , Taenia/immunology , Time Factors
15.
J Thorac Cardiovasc Surg ; 117(1): 54-63; discussion 63-5, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9869758

ABSTRACT

OBJECTIVES: Our aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma. METHODS: From 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy. RESULTS: Forty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P =.0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P =.02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P =.004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P <.0001), positive resection margins (OR 1.7, CI 1.2-2.6; P =.0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2; P =.0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P =.013). A previously published staging system using these variables stratified survival (P <.05). CONCLUSIONS: (1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival.


Subject(s)
Mesothelioma/surgery , Pleural Neoplasms/surgery , Pneumonectomy , Adult , Aged , Chemotherapy, Adjuvant , Female , Humans , Lymphatic Metastasis , Male , Mesothelioma/mortality , Mesothelioma/pathology , Middle Aged , Neoplasm Staging , Pleural Neoplasms/mortality , Pleural Neoplasms/pathology , Prognosis , Proportional Hazards Models , Radiotherapy, Adjuvant , Retrospective Studies , Survival Analysis , Treatment Outcome
17.
Cancer ; 82(8): 1578-84, 1998 Apr 15.
Article in English | MEDLINE | ID: mdl-9554537

ABSTRACT

BACKGROUND: In a prior Cancer and Leukemia Group B (CALGB) Phase II trial of patients with advanced, previously untreated mesothelioma, dihydro-5-azacytidine (DHAC) demonstrated a 17% response rate, including 1 complete response, with only mild myelosuppression. This Phase II study (CALGB 9031) was conducted to determine the effectiveness of and toxicities that would result from adding cisplatin to DHAC administered to the same patient population. METHODS: Thirty-six patients were treated with concurrent DHAC at 1500 mg/m2/day for 5 days by continuous infusion and cisplatin 15 mg/m2 daily for 5 days. Therapy was repeated every 3 weeks. Cisplatin was to be increased to 20 mg/m2 daily in subsequent cycles if toxicity was minimal. Therapy was continued until disease progression or excessive toxicity mandated discontinuation. RESULTS: Overall, 5 objective responses were observed in 29 evaluated patients (objective response rate, 17%). The median duration of response was 6.6 months. Median survival was 6.4 months, with a median time to clinical failure of 2.7 months. The major toxicity noted was significant chest/pericardial pain, as was observed with DHAC alone. There were 2 early deaths of unknown cause on Days 9 and 17 of therapy, respectively. Significant leukopenia was observed in 29% of patients, but there were no neutropenic fevers. CONCLUSIONS: The addition of cisplatin to DHAC did not increase the response rate over that observed with DHAC alone in patients with mesothelioma; however, it did increase toxicity, especially leukopenia. This combination is not recommended for further studies involving mesothelioma patients.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Azacitidine/analogs & derivatives , Cisplatin/therapeutic use , Mesothelioma/drug therapy , Pleural Neoplasms/drug therapy , Adult , Aged , Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Azacitidine/adverse effects , Azacitidine/therapeutic use , Chest Pain/chemically induced , Cisplatin/adverse effects , Female , Humans , Leukopenia/chemically induced , Male , Mesothelioma/mortality , Mesothelioma/pathology , Middle Aged , Pleural Neoplasms/mortality , Pleural Neoplasms/pathology , Prognosis , Survival Analysis
18.
Angiology ; 49(4): 259-65, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9555928

ABSTRACT

The purpose of this study was to compare the results of extra-anatomic femorofemoral crossover bypass grafting to the anatomic iliofemoral bypass grafting procedure in the treatment of patients with unilateral iliac artery occlusive disease with respect to patency and limb salvage. The records of all patients with unilateral iliac artery disease who underwent revascularization between January 1988 and December 1995 at the University of Iowa Hospitals and Clinics (UIHC) were retrospectively reviewed; 108 patients were identified and divided into two groups. Group I (n=68; male/female=44/24) was composed of all patients who underwent a femorofemoral crossover extra-anatomic bypass. All patients who underwent an iliofemoral anatomic bypass constituted group II (n=40; male/female=24/16). The mean age for group I was 60 years (range 28-87) and for group II, 54 years (range 14-86). The medical risk factors between both groups were comparable. Except for the higher incidence of gangrene in group II the indications for surgery were comparable between both groups. A polytetrafluoroethylene graft was used in 88% of group I patients and in 90% of group II patients (NS). In the remaining patients, an autogenous vein conduit was used. Two patients from group I (2.9%) died in the perioperative period (NS). Graft patency was assessed by clinical evaluation, Doppler-derived ankle/brachial indices, and color duplex imaging. The cumulative primary and secondary patency rates, limb salvage, and patient survival were calculated by use of life table analysis (SE<0.1). The need for simultaneous outflow and inflow procedures at the time of surgery was comparable between both groups. The proportion of patients who underwent further revascularization during follow-up was also comparable. The 5-year primary and secondary graft patency rates were 81.7% and 90.3%, in group I and 61.3% and 80.5% in group II. Although the difference between both groups was not significant there was a tendency toward higher rates with femorofemoral bypass. The 5-year survival rates of 80.3% for group I and 73.3% for group II were comparable. These data suggest that there is no significant difference in the long-term results between the femorofemoral crossover bypass grafts and iliofemoral grafts. Both procedures result in acceptable patency and limb salvage rates. The femorofemoral bypass is, however, more attractive, for it can be performed under local anesthesia if needed and does not involve the creation of the retroperitoneal incision necessary with the iliofemoral bypass.


Subject(s)
Arterial Occlusive Diseases/surgery , Blood Vessel Prosthesis Implantation/methods , Femoral Artery/surgery , Iliac Artery/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Arterial Occlusive Diseases/diagnostic imaging , Blood Vessel Prosthesis , Chi-Square Distribution , Evaluation Studies as Topic , Female , Femoral Artery/diagnostic imaging , Follow-Up Studies , Gangrene/surgery , Humans , Iliac Artery/diagnostic imaging , Incidence , Leg/blood supply , Leg/diagnostic imaging , Life Tables , Male , Middle Aged , Polytetrafluoroethylene , Regional Blood Flow , Reoperation , Retrospective Studies , Risk Factors , Survival Rate , Transplantation, Autologous , Ultrasonography, Doppler, Color , Ultrasonography, Doppler, Duplex , Vascular Patency , Veins/transplantation
19.
Angiology ; 49(4): 275-8, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9555930

ABSTRACT

The role of carotid endarterectomy (CEA) in stroke prevention is now better defined. However, its role in patients older than 79 years of age is controversial. This group of patients has been excluded in most clinical trials. In this study the authors reviewed their experience with CEA patients >79 years old. The records of all patients older than 79 years of age who underwent a CEA in a recent time period from January 1988 to December 1996 were retrospectively reviewed. Forty-one patients (31 men, 10 women) were identified by computer search. The indication for operation included transient ischemic attack in 12 (29.3%), amaurosis fugax in nine (22%), stroke in two (4.9%), and nonhemispheric symptoms in three (7.3%). Fifteen patients (36.6%) were asymptomatic. Medical risk factors included coronary artery disease in 26 (63.4%), hypertension in 22 (53.7%), and smoking in 12 (29.3%). The procedure was performed under EEG monitoring in all patients. General anesthesia was administered in 37 (90%) and regional anesthesia in four (10%). Shunts were used in four (10%) patients. The internal carotid artery was patched in 16 patients (39%). One patient (2.4%) developed a perioperative stroke and only one patient developed perioperative myocardial infarction (MI). None of the patients died within 30 days of surgery. In addition to the one MI case, five patients developed minor complications. The average length of time for stay after CEA was 3.4 days. Patients were followed up for an average of 20.7 months. Six patients died during follow-up. Four of those died from an MI and two from a stroke. The authors conclude that with proper selection of patients, CEA is safe in the octogenarian. Age alone should not be a contraindication for CEA.


Subject(s)
Aging , Endarterectomy, Carotid , Aged , Aged, 80 and over , Anesthesia, Conduction , Anesthesia, General , Blindness/surgery , Carotid Artery, Internal/surgery , Cause of Death , Cerebrovascular Disorders/etiology , Cerebrovascular Disorders/prevention & control , Cerebrovascular Disorders/surgery , Contraindications , Coronary Disease/complications , Electroencephalography , Endarterectomy, Carotid/adverse effects , Endarterectomy, Carotid/methods , Female , Follow-Up Studies , Humans , Hypertension/complications , Intraoperative Complications , Ischemic Attack, Transient/surgery , Length of Stay , Male , Monitoring, Intraoperative , Myocardial Infarction/etiology , Patient Selection , Retrospective Studies , Risk Factors , Safety , Smoking/adverse effects , Survival Rate
20.
Chest ; 113(3): 723-31, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9515850

ABSTRACT

PURPOSE: To examine the individual and joint effect of various pretreatment clinical characteristics on the survival of patients with mesothelioma treated by the Cancer and Leukemia Group B (CALGB). PATIENTS AND METHODS: Between June 1984 and September 1994, 337 patients with malignant mesothelioma and no prior chemotherapy were accrued to seven phase II studies conducted by the CALGB which screened the efficacy of 10 treatment regimens or dose levels. The eligibility criteria for all studies were virtually identical. Patient characteristics include the following: age older than 60 years (63%); male (83%); performance status (PS) of 0 or 1 (81%); chest pain (60%); definite asbestos exposure (62%); >5% weight loss (41%); and pleural involvement (94%). Median survival time (MST) for the 10 treatment regimens ranged from 3.9 to 9.8 months (overall=7.2; 95% confidence interval [CI], 6.5 to 8.3), with 1-year survival between 14% and 50% (overall=27%; 95% CI, 23 to 33%). RESULTS: Cox survival models and exponential regression trees were used to examine the prognostic importance of pretreatment patient characteristics. Univariate analyses show that patients with poor Eastern Cooperative Oncology Group PS, chest pain, dyspnea, platelet count (PLT) >400,000/microL, weight loss, serum lactate dehydrogenase (LDH) level >500 IU/L, pleural involvement, low hemoglobin (HGB) level, high WBC count, and increasing age over 75 years have a worse prognosis. With decreasing risk ratio, multivariate Cox analyses showed that pleural involvement, LDH >500 IU/L, poor PS, chest pain, PLT >400,000/microL, nonepithelial histology, and increasing age older than 75 years jointly predict poor survival. PS was the most important prognostic split in the regression tree. Terminal nodes were amalgamated to form six distinct prognostic subgroups with MST (2-year survival) of 13.9 (38%) in 36 patients, 9.5 (21%) in 36 patients, 9.2 (10%) in 146 patients, 6.5 (3%) in 33 patients, 4.4 (0%) in 73 patients, and 1.4 (0%) in 13 patients (p<0.0001). CONCLUSIONS: The subgroup with the best survival (MST=13.9 months) included patients with PS=0 and age younger than 49 years, and patients with PS=0, age of 49 years or older, and HGB > or =14.6. The worst survival (MST= 1.4 months) occurred for patients with PS= 1/2 and WBC > or =15.6/microL.


Subject(s)
Mesothelioma/mortality , Aged , Female , Humans , Male , Mesothelioma/drug therapy , Middle Aged , Pleural Neoplasms/drug therapy , Pleural Neoplasms/mortality , Regression Analysis , Risk Factors , Survival Analysis , Survival Rate
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