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1.
Musculoskelet Surg ; 105(1): 105-110, 2021 Apr.
Article in English | MEDLINE | ID: mdl-31989533

ABSTRACT

BACKGROUND: An arthroscopic meniscectomy is one of the most common orthopedic procedures in athletes. Return to play rates and deficits in muscle function have been reviewed after meniscectomy, but no study has reviewed functional performance after an isolated partial meniscectomy. HYPOTHESIS/PURPOSE: To compare the performance of elite-level basketball players after a partial meniscectomy to a control group of players with no previous reported knee injury. We believe that there is no difference between the two groups in functional performance. STUDY DESIGN: Case Series. METHODS: Functional performance results from the National Basketball Association (NBA) combine were reviewed between 2000 and 2015. Twelve out of 1092 players were found to have undergone a partial meniscectomy prior to competing in the NBA combine. The partial meniscectomy group was compared to an age-, size-, and position-matched control group with respect to functional performance testing such as the shuttle run test, lane agility test, ¾ court sprint, vertical jump (no step), and vertical jump (max). RESULTS: The meniscectomy and the control groups that there was no significant difference between the two groups in agility, quickness, sprinting, and jumping ability. However, there was a - 0.596 spearman correlation between months after surgery and agility (p = 0.041), while there was a + 0.690 and + 0.650 spearman correlation between both months after surgery and standing vertical and max vertical (p = 0.013 and p = 0.022). CONCLUSIONS: Athletes competing in the NBA combine who have undergone a partial meniscectomy perform as well as uninjured athletes in all NBA combine performance testing. Furthermore, as athletes are further out from surgery, they have an improvement in both standing and max vertical jump.


Subject(s)
Basketball , Knee Injuries , Arthroscopy , Athletes , Humans , Meniscectomy
2.
Comput Biol Med ; 116: 103529, 2020 01.
Article in English | MEDLINE | ID: mdl-31715382

ABSTRACT

Chronic lower lumbar pain has been associated with elevated bone metabolic activity in the spine. Diagnosis of bone metabolic activity is currently through integrating Positron Emission Tomography (PET) with Sodium Fluoride (18F-NaF) biomarkers. It has been reported that numerous observable pathologies including lumbar fusion, disc abnormalities and scoliosis have often been associated with increased 18F-NaF uptake. The aim of this study was to identify what features of lower lumbar shape most strongly correlate with 18F-NaF uptake. Following a principal component analysis of 23 patients who presented with lumbar pain and underwent 18F-NaF PET-CT, it was revealed that three modes interpreted as (i) sacral tilt, (ii) vertebral disc spacing and (iii) spine size were the three characteristics that described 88.7% of spine shape in our study population. 18F-NaF was described by two modes including 18F-NaF intensity and spatial variation (anterior-inferior to posterior-superior). 18F-NaF was most sensitive to sacral tilt followed by vertebral disc spacing. A predictive model derived from that spine population was able to predict 18F-NaF 'hot-spot' locations with 85 ±â€¯5% accuracy and with 71 ±â€¯3% accuracy for the 18F-NaF magnitude. These results suggest that patients reporting with lower lumbar pain and who present with increased sacral tilt profiles and/or reduced disc spacing are good candidates for further 18F-NaF PET-CT imaging, evidenced by the high association between those shape profiles and 18F-NaF uptake.


Subject(s)
Fluorine Radioisotopes/pharmacokinetics , Lumbar Vertebrae , Sodium Fluoride/pharmacokinetics , Adult , Biomarkers , Female , Fluorine Radioisotopes/therapeutic use , Humans , Image Processing, Computer-Assisted , Low Back Pain , Lumbar Vertebrae/anatomy & histology , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/metabolism , Male , Middle Aged , Positron Emission Tomography Computed Tomography/methods , Principal Component Analysis , Sodium Fluoride/therapeutic use
4.
Eur J Surg Oncol ; 43(7): 1219-1227, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27923591

ABSTRACT

BACKGROUND: Thyroid nodules are usually diagnosed using fine-needle aspiration (FNA). The sensitivity limitations of FNA result in 10-30% of nodules being classified as "indeterminate". The BRAFV600E mutation is associated with papillary thyroid carcinoma (PTC). We conducted a systemic review and meta-analysis to evaluate the diagnostic utility of the BRAFV600E mutation in indeterminate nodules. METHOD: PUBMED and EMBASE were searched for studies testing for the BRAFV600E involving indeterminate nodules (Thy3a, Thy3f, Thy4) and containing information on final surgical histopathology. Thirty two studies involving 3150 indeterminate nodules were included in the analysis. RESULTS: The overall sensitivity and specificity for BRAFV600E for the diagnosis of thyroid malignancy was 0.40 (95% CI: 0.32-0.48) and 1.00 (95% CI: 0.98-1.00) respectively. The diagnostic odds ratio (DOR) was 205.4 (95% CI: 40.1-1052). With a Fagan plot, the post-test probability of thyroid cancer, given a negative mutation was 6%, but this rose to 92% with a positive result. On subgroup analysis, for Thy3a nodules, the pooled sensitivity and specificity for thyroid malignancy was 0.21 (95% CI: 0.13-0.34) and 1.00 (95% CI: 0.98-1.00). For Thy3f nodules, the pooled sensitivity and specificity was 0.09 (95% CI: 0.03-0.20) and 1.00 (95% CI: 0.05-1.00) respectively. For Thy4 nodules, the corresponding sensitivity and specificity was 0.58 (95% CI: 0.5-0.64) and 0.99 (95% CI: 0.95-1.00) respectively. CONCLUSIONS: Despite a high specificity for thyroid cancer, BRAFV600E mutation has a low overall sensitivity and therefore has a limited diagnostic value as a single screening test.


Subject(s)
DNA, Neoplasm/analysis , Mutation , Proto-Oncogene Proteins B-raf/genetics , Thyroid Nodule/diagnosis , Thyroid Nodule/genetics , DNA Mutational Analysis , Humans , Sensitivity and Specificity , Thyroid Nodule/pathology
5.
BMJ Open ; 5(6): e006678, 2015 Jun 08.
Article in English | MEDLINE | ID: mdl-26056120

ABSTRACT

OBJECTIVES: We examined the utility of January 2004 to April 2014 Google Trends data from information searches for cancer screenings and preparations as a complement to population screening data, which are traditionally estimated through costly population-level surveys. SETTING: State-level data across the USA. PARTICIPANTS: Persons who searched for terms related to cancer screening using Google, and persons who participated in the Behavioral Risk Factor Surveillance System (BRFSS). PRIMARY AND SECONDARY OUTCOME MEASURES: (1) State-level Google Trends data, providing relative search volume (RSV) data scaled to the highest search proportion per week (RSV100) for search terms over time since 2004 and across different geographical locations. (2) RSV of new screening tests, free/low-cost screening for breast and colorectal cancer, and new preparations for colonoscopy (Prepopik). (3) State-level breast, cervical, colorectal and prostate cancer screening rates. RESULTS: Correlations between Google Trends and BRFSS data ranged from 0.55 for ever having had a colonoscopy to 0.14 for having a Pap smear within the past 3 years. Free/low-cost mammography and colonoscopy showed higher RSV during their respective cancer awareness months. RSV for Miralax remained stable, while interest in Prepopik increased over time. RSV for lung cancer screening, virtual colonoscopy and three-dimensional mammography was low. CONCLUSIONS: Google Trends data provides enormous scientific possibilities, but are not a suitable substitute for, but may complement, traditional data collection and analysis about cancer screening and related interests.


Subject(s)
Data Collection/methods , Early Detection of Cancer , Information Seeking Behavior , Mass Screening , Neoplasms/diagnosis , Patient Acceptance of Health Care , Search Engine/trends , Adolescent , Adult , Awareness , Colonoscopy , Costs and Cost Analysis , Female , Health Behavior , Humans , Internet , Male , Mammography , Surveys and Questionnaires , Vaginal Smears
6.
Chemosphere ; 109: 7-13, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24873700

ABSTRACT

The investigation presents the observations on the use of cement beads for the immobilization of TiO2 for the degradation of herbicide isoproturon. The immobilized system was effective in degrading and mineralizing the herbicide for continuous thirty cycles without losing its durability. Catalyst was characterized by SEM-EDAX for checking the durability of the catalyst. The degradation rate followed first order kinetics as measured by change in absorption intensity in UV range as well as HPLC analysis. Two rounds of TiO2 coating on inert cement beads with average diameter 1.5cm at UV Intensity 25Wm(-2) calcined at 400°C were the optimized conditions for the degradation of herbicide isoproturon. More than 90% TOC and COD reduction along with ammonium ions generation (80%) confirmed the mineralization of isoproturon. Fixed bed baffled reactor studies under solar irradiations using the TiO2 immobilized beads confirmed 85% degradation after 6h. LC-MS studies confirmed the intermediates formation and their subsequent degradation using immobilized system.


Subject(s)
Herbicides/chemistry , Phenylurea Compounds/chemistry , Titanium/chemistry , Catalysis , Chemistry/instrumentation , Chromatography, High Pressure Liquid , Hydrogen Peroxide/chemistry , Kinetics , Mass Spectrometry , Oxidation-Reduction , Temperature , Ultraviolet Rays
7.
Bone Marrow Transplant ; 47(12): 1513-9, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22580767

ABSTRACT

Rabbit anti-thymocyte globulin (ATG) is used as prophylaxis against GVHD following allogeneic hematopoietic cell transplantation (HCT). At our institution, ATG is exclusively used in the conditioning of matched unrelated donor (URD) transplant recipients. A total of 50 URD HCT recipients who received ATG (ATG group) were retrospectively compared with 48 matched related donor (MRD) HCT recipients who did not receive ATG (no ATG group). There were no significant differences between the groups in rates of day 100 mortality, acute GVHD or relapse. Chronic GVHD incidence was significantly lower in the ATG group (P = 0.007). At a median follow-up of 36 months in the entire cohort, 50% patients are alive in the ATG group and 63% of the patients are alive in the no ATG group (P = 0.13). We conclude that the administration of ATG to patients undergoing URD HCT preserves the anti-leukemia benefit of the transplant, while reducing the risk of developing GVHD, resulting in OS rates that are comparable to MRD HCT recipients.


Subject(s)
Antilymphocyte Serum/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Cohort Studies , Female , Graft vs Host Disease/prevention & control , Humans , Male , Middle Aged , Myelodysplastic Syndromes/surgery , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Randomized Controlled Trials as Topic , Retrospective Studies , Survival Analysis , Tissue Donors , Transplantation, Homologous , Treatment Outcome , Unrelated Donors
8.
Environ Monit Assess ; 172(1-4): 571-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20169406

ABSTRACT

The village ponds were used for storing rainwater for animals and recharging of underground water. Recent developments like public water supply for household purpose, provision of household wastewater concrete channels, and toilet septic tanks have polluted the village ponds. The infiltration of water has decreased due to non-cleaning of silt from the pond beds. Increased discharge of wastewater from households, coupled with a low infiltration rate, has inundated these ponds. People have abandoned the use of this water for animals. An effort has been made to assess the suitability of this water for irrigation in the vicinity so as to clean these ponds. Seventy-eight water samples were collected from the village ponds in the Ludhiana district of Punjab. The samples were analyzed for total solids (TS), total dissolved solids (TDS), total suspended solids (TSS), biological oxygen demand (BOD), chemical oxygen demand (COD), electrical conductivity (EC), residual sodium carbonate (RSC), nitrogen, water soluble P and K, as well as micronutrients and pollutant elements. The total solids content of these waters were on the higher side. Considering TSS, BOD, and COD, some of these waters are unsafe for their disposal in river or water bodies. Electrical conductivity ranged from 693 to 5050 µmhos/cm, and RSC varied between -1.9 and 22.8 meq/l. The inorganic N (NH+4+ NO-3-N) and total Kjeldahl N ranged from 3 to 30 and 8 to 41 mg/l, respectively. The amount of micronutrients (Zn, Cu, Fe, and Mn) present in pond water indicated its high nutrient value. The content of the pollutant elements such as nickel, cadmium, and lead was below the maximum permissible limits, thereby indicating its suitability for irrigation. According to the EC and RSC criteria, 18% of the samples were fit, 31% were marginal, and 51% were unfit for irrigation. The data indicate that these waters are a good source of nutrients for agriculture.


Subject(s)
Environmental Monitoring/methods , Fresh Water/analysis , Water Pollutants, Chemical/analysis , Water Supply/analysis , Carbonates/analysis
9.
Bone Marrow Transplant ; 42(11): 723-31, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18711352

ABSTRACT

Murine studies using anti-T-cell antibodies for conditioning in allogeneic SCT demonstrate engraftment with low rates of GVHD. On the basis of this preclinical model, we conditioned 30 patients with advanced hematologic malignancies with rabbit antithymocyte globulin (ATG) and TBI, to reduce rates of fatal acute GVHD. Patients were enrolled in two sequential groups: cohort 1 received ATG 10 mg/kg in divided doses (days -4 to -1)+200 cGy TBI (n=16), and cohort 2 received ATG (days -10 to -7)+450 cGy TBI (n=14). Median donor blood chimerism for the combined group was 94, 93 and 93% in the first, second and third months after transplant. Only three developed grade II acute GVHD despite 43% of patients receiving unrelated donor transplants. One-year survival was 71+/-11 and 54+/-14%, respectively, in recipients of related and unrelated donor SCT. Donor lymphocyte infusions were needed in 12 patients for the management of relapse and for mixed donor-recipient chimerism in 4 patients. We conclude that 10 mg/kg ATG and TBI allows engraftment with a low risk of acute GVHD; however, further dose optimization of ATG is required to achieve a balance between GVHD and disease relapse.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Graft vs Host Disease/therapy , Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Adult , Aged , Animals , Antilymphocyte Serum/metabolism , Cohort Studies , Female , Humans , Lymphocytes/cytology , Male , Middle Aged , Rabbits , Treatment Outcome
10.
Vet Rec ; 162(9): 275-7, 2008 Mar 01.
Article in English | MEDLINE | ID: mdl-18310560

ABSTRACT

Twelve of 46 female buffaloes with abdominal disorders were diagnosed with omasal impaction. They had been fed finely chopped machine-prepared straw. They were characterised by anorexia, an absence of defecation, abdominal distension, ruminal hypomotility or atony and a suspension of rumination. Omasal impaction was confirmed upon left flank laparorumenotomy on the basis of the size of the omasum and the consistency of its contents. After ruminal evacuation, a long flexible pipe was introduced through the reticulo-omasal orifice and the omasal contents were flushed back into the rumen with water under moderate pressure. Hyponatraemia, hypochloraemia, hypokalaemia and hypophosphataemia were consistent features in most cases. However, two buffaloes that later died had lower levels of plasma chloride, no reticulo-omasal orifice tone and were in an advanced stage of pregnancy. The level of total protein in peritoneal fluid was higher than normal, but the total white cell count was within the normal range. All the animals started passing faeces 36 to 48 hours after surgery. The presence of reticulo-omasal orifice tone and a plasma chloride level above 75 mmol/l were indicators of a good prognosis.


Subject(s)
Buffaloes , Chlorides/blood , Omasum/pathology , Omasum/surgery , Stomach Diseases/veterinary , Animals , Blood Chemical Analysis/veterinary , Female , Laparotomy/veterinary , Omasum/metabolism , Prognosis , Rumen/metabolism , Rumen/pathology , Rumen/surgery , Stomach Diseases/blood , Stomach Diseases/diagnosis , Stomach Diseases/surgery , Treatment Outcome
11.
Transpl Infect Dis ; 9(2): 89-96, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17461992

ABSTRACT

We describe the clinical courses of 3 patients with hematologic malignancies (2 with acute myelogenous leukemia and 1 with multiple myeloma) who developed invasive fungal infections due to uncommon molds (Alternaria spp., Paecilomyces lilacinus, and Zygomycetes). Breakthrough invasive fungal infections of the sinus (n=1), lung (n=3), and pericardium (n=1) developed despite fluconazole prophylaxis and failed to respond to treatment with other licensed antifungal therapies, including amphotericin B (n=3), caspofungin (n=2), and voriconazole (n=3), and surgical intervention (n=2). Salvage therapy with posaconazole oral suspension resulted in successful outcomes in all 3 patients, who subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) while on continued posaconazole therapy. The median duration of posaconazole treatment before HSCT was 5 months (range: 1.5-6 months). Posaconazole salvage therapy allowed successful allogeneic HSCT in 3 patients with refractory invasive mold infections.


Subject(s)
Antifungal Agents/therapeutic use , Mycoses/drug therapy , Triazoles/therapeutic use , Adult , Female , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Multiple Myeloma/therapy , Prospective Studies , Salvage Therapy , Transplantation, Homologous
12.
Bone Marrow Transplant ; 38(11): 757-64, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17057729

ABSTRACT

Outpatient hematopoietic stem cell transplants (HSCT) are usually performed in patients receiving minimally mucotoxic preparative regimens; total body irradiation (TBI)-based regimens typically are excluded. To improve resource utilization and patient satisfaction, we developed a totally outpatient HSCT program for TBI regimens and compared outcomes for our first 100 such transplants to 32 performed as in-patients during the same interval, for caregiver or financial reasons. Symptoms were managed predominately with oral agents; pain management consisted of transdermal fentanyl and oral morphine solution. Except for more unmarried in-patients, the two groups were matched. Time to engraftment, severity of mucositis and transplant duration were identical for the two groups. Twenty-seven of the outpatients were admitted (median-6 days), primarily for progressing infection. Thus 92% of all transplant days were outpatient. There were no septic episodes or hospital admissions for pain management. There were no deaths to day 30 in either group and 100-day survival was identical. There was a mean cost savings of Dollars 16,000 per outpatient transplant and outpatient patient/caregiver quality of life was similar to that reported for in-patients. Patients undergoing severely mucotoxic regimens can be safely transplanted in an outpatient setting with a significant cost saving, with no increase in morbidity or mortality.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Outpatients , Whole-Body Irradiation/methods , Adult , Cost Savings , Female , Follow-Up Studies , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/economics , Humans , Kaplan-Meier Estimate , Male , Pain/etiology , Pain Management , Patient Admission/economics , Patient Admission/statistics & numerical data , Quality of Life , Transplantation, Autologous , Whole-Body Irradiation/adverse effects
13.
Leuk Lymphoma ; 47(7): 1369-78, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16923571

ABSTRACT

Heat shock protein 90 (HSP90) is required for structural folding and maintenance of conformational integrity of various proteins, including several associated with cellular signaling. Recent studies utilizing 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, demonstrated an antitumor effect in solid tumors. To test whether HSP90 could be targeted in multiple myeloma (MM) patients, we first investigated expression of HSP90 by immunofluorescence and flow cytometric analysis in a myeloma cell line (U266) and primary myeloma cells. Following demonstration of HSP90 expression in myeloma cells, archival samples of 32 MM patients were analysed by immunoperoxidase staining. Myeloma cells in all patients showed strong cytoplasmic expression of HSP90 in all samples and 55% also demonstrated concurrent nuclear immunopositivity. Treatment of U266 and primary MM cells with 17AAG resulted in significantly increased apoptosis compared to untreated control cells. Analysis of anti-apoptotic BCL2 family proteins and akt in MM cells incubated with 17-AAG revealed down-regulation of BCL-2, BCL-XL, MCL-1 and akt. Furthermore, although a low concentration of bortezomib resulted in no cell death, a combination of 17AAG and bortezomib treatment revealed a synergistic apoptotic effect on the U266 cell line. These data suggest that targeted inhibition of HSP90 may prove to be a valid and innovative strategy for the development of future therapeutic options for MM patients.


Subject(s)
Apoptosis , Benzoquinones/pharmacology , Enzyme Inhibitors/pharmacology , Gene Expression Regulation, Neoplastic , HSP90 Heat-Shock Proteins/antagonists & inhibitors , HSP90 Heat-Shock Proteins/biosynthesis , Lactams, Macrocyclic/pharmacology , Multiple Myeloma/drug therapy , Multiple Myeloma/metabolism , Cell Line, Tumor , Cell Survival , Flow Cytometry , Humans , Microscopy, Fluorescence , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism
14.
Bone Marrow Transplant ; 37(5): 479-84, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16435021

ABSTRACT

Patients referred for hematopoietic stem cell transplantation (HSCT) often have knowledge deficits about their disease and overestimate their prognosis making it difficult initially to discuss potentially life-threatening transplant options. To determine patients' understanding of their disease and the adequacy of a 3-h consultation at our center, we developed a survey that measured perceived knowledge deficits of disease, prognosis, and emotional status before and after their initial consultation. Ninety nine consecutive eligible patients completed the survey. Although 76.7% claimed adequate information about their disease pre-HCST visit, 51.5 and 41.4% respectively lacked knowledge about their 1-year prognosis with and without any therapy. After the visit, 66.7% of the patients had obtained enough information to make an informed decision regarding HSCT versus 23.2% pre-visit, and a significant reduction in the need for further information was reported by 53.5% of patients (P<0.001). Patients were not overwhelmed or confused by the visit and there was a small but significant decrease in negative affect. Measures to increase patients understanding of their disease and its prognosis pre-HSCT consultation visit are warranted; however, a 3-h consultation visit provides the majority of patients with sufficient information to make an informed decision about the risk/benefit ratio of HSCT.


Subject(s)
Hematologic Diseases , Hematopoietic Stem Cell Transplantation , Patient Education as Topic/standards , Referral and Consultation/standards , Data Collection , Decision Making , Health Status , Humans , Informed Consent/standards , Prognosis , Risk Assessment
15.
Bone Marrow Transplant ; 35(3): 261-4, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15558039

ABSTRACT

A second allogeneic hematopoietic stem cell transplant (HSCT) for relapsed hematologic malignancies is an option in select patients after an initial allograft has failed. If the original donor is not available, a different donor may have to be considered. We report our experience of performing a second allogeneic HSCT using a different donor in patients with relapsed leukemia and lymphoma. In a 5-year period, six patients underwent a second allograft with myeloablative conditioning using a different donor. Four of these were retransplanted using a matched-unrelated donor. Four of the patients (67%) remain progression-free at a median follow-up of 32 months (range 3-72). There were no cases of transplant-related mortality. We conclude that a second allogeneic HSCT using a different donor is a viable option for selected patients relapsing after an allograft if the original donor is not available.


Subject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Salvage Therapy/methods , Tissue Donors , Adolescent , Adult , Disease-Free Survival , Feasibility Studies , Female , Graft Survival , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation/adverse effects , Histocompatibility , Humans , Incidence , Leukemia/therapy , Lymphoma/therapy , Male , Middle Aged , Retrospective Studies , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods , Transplantation, Homologous
16.
Phys Rev E Stat Nonlin Soft Matter Phys ; 67(6 Pt 2): 066501, 2003 Jun.
Article in English | MEDLINE | ID: mdl-16241361

ABSTRACT

VISA (Visible to Infrared SASE Amplifier) is a high-gain self-amplified spontaneous emission (SASE) free-electron laser (FEL), which achieved saturation at 840 nm within a single-pass 4-m undulator. The experiment was performed at the Accelerator Test Facility at BNL, using a high brightness 70-MeV electron beam. A gain length shorter than 18 cm has been obtained, yielding a total gain of 2 x 10(8) at saturation. The FEL performance, including the spectral, angular, and statistical properties of SASE radiation, has been characterized for different electron beam conditions. Results are compared to the three-dimensional SASE FEL theory and start-to-end numerical simulations of the entire injector, transport, and FEL systems. An agreement between simulations and experimental results has been obtained at an unprecedented level of detail.

17.
Leukemia ; 16(9): 1835-7, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12200700

ABSTRACT

Arsenic has been used since ancient times as a therapeutic agent. However, until recently its use in modern medicine has been restricted to the treatment of a limited number of parasitic infections. In the early 1990s, reports from China described impressive results with arsenic trioxide in patients with de novo, relapsed, and refractory acute promyelocytic leukemia (APL). Other investigators subsequently confirmed these results leading to approval of its use for relapsed or refractory APL in the United States. Investigations of this agent have demonstrated that its efficacy in APL and preclinical tumor models is dependent upon a number of mechanisms, including induction of apoptosis, effects on cellular differentiation, cell cycling, and tumor angiogenesis. Subsequent preclinical studies showed significant activity of arsenic trioxide in multiple myeloma (MM). Based on this, in a phase II trial, we have evaluated the activity of arsenic trioxide in 14 patients with relapsed MM, refractory to conventional salvage therapy. With the dose and schedule used, treatment with arsenic trioxide produced responses in three patients and prolonged stable disease in a fourth patient, with the longest response lasting 6 weeks. Although treatment was reasonably well tolerated, in these patients with extensive prior therapy, 11 developed cytopenia, five associated with infectious complications and three developed deep vein thromboses. The results of this small trial support further investigation of this novel drug for the treatment of patients with relapsed or refractory MM.


Subject(s)
Antineoplastic Agents/therapeutic use , Arsenicals/therapeutic use , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Oxides/therapeutic use , Adult , Aged , Antineoplastic Agents/adverse effects , Arsenic Trioxide , Arsenicals/adverse effects , Drug Evaluation , Humans , Middle Aged , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/pathology , Neutropenia/chemically induced , Oxides/adverse effects , Salvage Therapy , Treatment Outcome
18.
Blood Coagul Fibrinolysis ; 13(3): 187-92, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11943931

ABSTRACT

Thromboembolism is not uncommon in multiple myeloma (MM) patients on treatment, but its pathogenesis remains poorly understood. We report the results of a prospective randomized trial of 62 newly diagnosed MM patients tested at baseline for hypercoagulability and treated with intensive chemotherapy with or without thalidomide in a randomized fashion. During the induction phase, 12 patients (19%) developed evidence of deep venous thrombosis (DVT), which was significantly more common in the thalidomide arm (36%) than in the control group (3%) (P = 0.001). Fourteen patients (23%) were found to have a baseline-reduced response to activated protein C (APC) in the absence of factor V Leiden mutation. Using a Kaplan-Meier analysis, a significantly higher proportion of patients with APC resistance developed DVT (5/14 versus 7/38; P = 0.04) irrespective of thalidomide administration. The risk of DVT was highest (50%) in patients with APC resistance on thalidomide. None of the patients with normal APC response and not receiving thalidomide developed DVT. In conclusion, in this series, acquired APC resistance was present in almost one-quarter of newly diagnosed myeloma patients and significantly increased the risk of DVT.


Subject(s)
Activated Protein C Resistance/etiology , Multiple Myeloma/blood , Thrombophilia/etiology , Venous Thrombosis/epidemiology , Activated Protein C Resistance/epidemiology , Activated Protein C Resistance/genetics , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Coagulation Tests , Cisplatin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Factor V/analysis , Female , Hematopoietic Stem Cell Transplantation , Humans , Incidence , Life Tables , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Multiple Myeloma/therapy , Risk , Thalidomide/administration & dosage , Thalidomide/adverse effects , Thalidomide/pharmacology , Vincristine/administration & dosage
19.
Bone Marrow Transplant ; 29(5): 403-8, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11919730

ABSTRACT

Acquired factor VII (FVII) deficiency in the absence of vitamin K deficiency, oral anticoagulant therapy, synthetic liver dysfunction, or DIC is rare, with only a handful of cases thus far reported. In the period from 1990 to 1996 we identified eight patients with acquired FVII deficiency, all of whom presented with prolongation of the prothrombin time (PT) in the first 2 weeks following stem cell transplantation (SCT). The mean plasma FVII clotting activity (FVII:c) was 22% (range 8-35%) with an approximately equivalent reduction in FVII antigen (FVII:Ag) level. Mean plasma levels of fibrinogen and factors II, V, IX, and X were normal. Protein C activity was significantly depressed in only one of the three patients in whom it was measured. Several patients experienced bleeding complications, and hemorrhage directly accounted for death in two cases. Veno-occlusive disease of the liver developed in three patients. We conclude that FVII deficiency should be considered in the differential diagnosis of prolonged PT in patients who have recently undergone SCT. The mechanism of this acquired deficiency state remains to be defined.


Subject(s)
Factor VII Deficiency/diagnosis , Factor VII Deficiency/etiology , Stem Cell Transplantation/adverse effects , Adult , Child , Diagnosis, Differential , Factor VII Deficiency/complications , Female , Hematologic Diseases/complications , Hematologic Diseases/therapy , Hemorrhage/etiology , Hepatic Veno-Occlusive Disease/etiology , Humans , Male , Neoplasms/complications , Neoplasms/therapy , Protein C/metabolism , Prothrombin Time , Retrospective Studies , Treatment Outcome
20.
Blood ; 98(5): 1614-5, 2001 Sep 01.
Article in English | MEDLINE | ID: mdl-11520815

ABSTRACT

The occurrence of deep-vein thrombosis (DVT) in patients with newly diagnosed multiple myeloma, who were randomly assigned to receive identical induction chemotherapy with or without thalidomide, are reported in this study. The 2 study arms were comparable with respect to key myeloma prognostic factors and known risk factors for DVT. One hundred patients received induction chemotherapy including 4 cycles of continuous infusion of combinations of dexamethasone, vincristine, doxorubicin, cyclophosphamide, etoposide, and cisplatin, and each patient completed at least one induction cycle. DVT developed in 14 of 50 patients (28%) randomly assigned to receive thalidomide but in only 2 of 50 patients (4%) not given the agent (P =.002). All episodes of DVT occurred during the first 3 cycles of induction. Administration of thalidomide was resumed safely in 75% of patients receiving anticoagulation therapy. Thus, thalidomide given in combination with multiagent chemotherapy and dexamethasone is associated with a significantly increased risk of DVT, which appears to be safely treated with anticoagulation and does not necessarily warrant discontinuation of thalidomide.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Multiple Myeloma/drug therapy , Thalidomide/adverse effects , Venous Thrombosis/etiology , Adult , Aged , Anticoagulants/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Coagulation Factors/analysis , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Humans , Male , Middle Aged , Multiple Myeloma/complications , Risk , Risk Factors , Thalidomide/administration & dosage , Venous Thrombosis/drug therapy , Venous Thrombosis/epidemiology , Venous Thrombosis/prevention & control , Vincristine/administration & dosage , Vincristine/adverse effects
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