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1.
Mar Pollut Bull ; 181: 113880, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35843160

ABSTRACT

The TRopical Oil Pollution Investigations in Coastal Systems (TROPICS) experiment, conducted on the Caribbean coast of Panama, has become one of the most comprehensive field experiments examining the long-term impacts of oil and dispersed oil exposures in nearshore tropical marine environments. From the initial experiment through more than three decades of study and data collection visits, the intertidal and subtidal communities have exhibited significantly different impact and recovery regimes, depending on whether the sites were exposed to crude oil only or crude oil treated with a chemical dispersant. This review provides a synopsis of the original experiment and a cumulative summary of the results and observations, illustrating the environmental and ecosystem trade-offs of chemical dispersant use in mangrove, seagrass, and coral reef environments.


Subject(s)
Petroleum Pollution , Petroleum , Caribbean Region , Coral Reefs , Ecosystem
2.
Langmuir ; 34(8): 2865-2875, 2018 02 27.
Article in English | MEDLINE | ID: mdl-29377702

ABSTRACT

Porous substrates have the ability to transport liquids not only laterally on their open surfaces but also transversally through their thickness. Directionality of the fluid transport can be achieved through spatial wettability patterning of these substrates. Different designs of wettability patterns are implemented herein to attain different schemes (modes) of three-dimensional transport in a high-density paper towel, which acts as a thin porous matrix directing the fluid. All schemes facilitate precise transport of metered liquid microvolumes (dispensed as droplets) on the surface and through the substrate. One selected mode features lateral fluid transport along the bottom surface of the substrate, with the top surface remaining dry, except at the initial droplet dispension point. This configuration is investigated in further detail, and an analytical model is developed to predict the temporal variation of the penetrating drop shape. The analysis and respective measurements agree within the experimental error limits, thus confirming the model's ability to account for the main transport mechanisms.

3.
Langmuir ; 34(5): 1899-1907, 2018 02 06.
Article in English | MEDLINE | ID: mdl-29323498

ABSTRACT

Spontaneous pumpless transport of droplets on wettability-confined tracks is important for various applications, such as rapid transport and mixing of fluid droplets, enhanced dropwise condensation, biomedical devices, and so forth. Recent studies have shown that on an open surface, a superhydrophilic track of diverging width, laid on a superhydrophobic background, facilitates the transport of water from the narrower end to the wider end at unprecedented rates (up to 40 cm/s) without external actuation. The spreading behavior on such surfaces, however, has only been characterized for water. Keeping in mind that such designs play a key role for a diverse range of applications, such as handling organic liquids and in point-of-care devices, the importance of characterizing the spreading behavior of viscous liquids on such surfaces cannot be overemphasized. In the present work, the spreading behavior on the aforementioned wettability-patterned diverging tracks was observed for fluids of different viscosities. Two dimensionless variables were identified, and a comprehensive relationship was obtained. Three distinct temporal regimes of droplet spreading were established: I), a Washburn-type slow spreading, II) a much faster Laplace pressure-driven spreading, and III), a sluggish density-augmented Tanner-type film spreading. The results offer design guidance for tracks that can pumplessly manage fluids of various viscosities and surface tensions.

4.
ACS Appl Mater Interfaces ; 10(5): 5038-5049, 2018 Feb 07.
Article in English | MEDLINE | ID: mdl-29304279

ABSTRACT

Liquid jet impingement on porous materials is particularly important in many applications of heat transfer, filtration, or in incontinence products. Generally, it is desired that the liquid not penetrate the substrate at or near the point of jet impact, but rather be distributed over a wider area before reaching the back side. A facile wettability-patterning technique is presented, whereby a water jet impinging orthogonally on a wettability-patterned nonwoven substrate is distributed on the top surface and through the porous matrix, and ultimately dispensed from prespecified points underneath the sample. A systematic approach is adopted to identify the optimum design that allows for a uniform distribution of the liquid on horizontally mounted substrates of ∼50 cm2 area, with minimal or no spilling over the sample edges at jet flow rates exceeding 1 L/min. The effect of the location of jet impingement on liquid distribution is also studied, and the design is observed to perform well even under offset jet impact conditions.

5.
Environ Toxicol Chem ; 36(1): 212-219, 2017 01.
Article in English | MEDLINE | ID: mdl-27311977

ABSTRACT

Previous research evaluating hydrocarbon toxicity to corals and coral reefs has generally focused on community-level effects, and results often are not comparable between studies because of variability in hydrocarbon exposure characterization and evaluation of coral health and mortality during exposure. Toxicity of the polycyclic aromatic hydrocarbon 1-methylnaphthalene to the coral Porites divaricata was assessed in a constant exposure toxicity test utilizing a novel toxicity testing protocol uniquely applicable to shallow-water corals, which considered multiple assessment metrics and evaluated the potential for post-exposure mortality and/or recovery. Acute and subacute effects (gross morphological changes, photosynthetic efficiency, mortality, and histologic cellular changes) were evaluated during pre-exposure (4 wk), exposure (48 h), and post-exposure recovery (4 wk) periods. Coral condition scores were used to determine a 48-h median effective concentration of 7442 µg/L. Significant physical and histological changes resulted from exposure to 640 µg/L and 5427 µg/L 1-methylnaphthalene, with a 1-d to 3-d delay in photosynthetic efficiency effects (ΔF/Fm). Pigmented granular amoebocyte area was found to be a potentially useful sublethal endpoint for this species. Coral mortality was used to estimate a 48-h median lethal concentration of 12 123 µg/L. Environ Toxicol Chem 2017;36:212-219. © 2016 SETAC.


Subject(s)
Anthozoa/drug effects , Environmental Monitoring/methods , Naphthalenes/toxicity , Water Pollutants, Chemical/toxicity , Animals , Anthozoa/growth & development , Coral Reefs , Environmental Monitoring/instrumentation , Equipment Design , Lethal Dose 50 , Models, Theoretical , Photosynthesis/drug effects , Toxicity Tests, Acute , Toxicity Tests, Subacute
6.
Nat Commun ; 2: 215, 2011.
Article in English | MEDLINE | ID: mdl-21364554

ABSTRACT

Ocean acidification causes declines in calcification rates of corals because of decreasing aragonite saturation states (Ω(arag)). Recent evidence also indicates that increasing sea surface temperatures may have already reduced growth and calcification rates because of the stenothermic threshold of localized coral populations. Density banding in coral skeletons provides a record of growth over the coral's lifespan. Here we present coral extension, bulk density and calcification master chronologies from seven subtropical corals (Montastraea faveolata) located in the Florida Keys, USA with a 60-year common period, 1937-1996. Linear trends indicate that extension increased, density decreased and calcification remained stable while the most recent decade was not significantly different than decadal averages over the preceding 50 years for extension and calcification. The results suggest that growth rates in this species of subtropical coral have been tolerant to recent climatic changes up to the time of collection (1996).


Subject(s)
Anthozoa/growth & development , Climate Change , Ecosystem , Animals , Calcification, Physiologic , Florida , Temperature
7.
Ann N Y Acad Sci ; 1162: 136-86, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19432648

ABSTRACT

Coral reefs are iconic, threatened ecosystems that have been in existence for approximately 500 million years, yet their continued ecological persistence seems doubtful at present. Anthropogenic modification of chemical and physical atmospheric dynamics that cause coral death by bleaching and newly emergent diseases due to increased heat and irradiation, as well as decline in calcification caused by ocean acidification due to increased CO(2), are the most important large-scale threats. On more local scales, overfishing and destructive fisheries, coastal construction, nutrient enrichment, increased runoff and sedimentation, and the introduction of nonindigenous invasive species have caused phase shifts away from corals. Already approximately 20% of the world's reefs are lost and approximately 26% are under imminent threat. Conservation science of coral reefs is well advanced, but its practical application has often been lagging. Societal priorites, economic pressures, and legal/administrative systems of many countries are more prone to destroy rather than conserve coral-reef ecosystems. Nevertheless, many examples of successful conservation exist from the national level to community-enforced local action. When effectively managed, protected areas have contributed to regeneration of coral reefs and stocks of associated marine resources. Local communities often support coral-reef conservation in order to raise income potential associated with tourism and/or improved resource levels. Coral reefs create an annual income in S-Florida alone of over $4 billion. Thus, no conflict between development, societal welfare, and coral-reef conservation needs to exist. Despite growing threats, it is not too late for decisive action to protect and save these economically and ecologically high-value ecosystems. Conservation science plays a critical role in designing effective strategies.


Subject(s)
Anthozoa , Conservation of Natural Resources , Ecosystem , Fisheries , Marine Biology , Seawater , Animals
9.
J Invertebr Pathol ; 95(2): 140-5, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17350649

ABSTRACT

We present evidence of cellular responses to increased sedimentation and temperature in Montastraea cavernosa collected off Broward County, Florida. We sampled corals from six different sites approximately, 500-1000 m off shore, 10-15m depth. Six samples were collected from four sites adjacent to areas of underwater marine dredging (project sites), while the remaining two samples were obtained far away from the influence of the marine dredging (control sites). SSTs around collection time ranged 0.6-0.9 degrees C over the 40-year monthly mean. All specimens collected at project sites exhibited histopathological evidence of mild to moderate sedimentation stress including changes in size and number of mucocytes in epidermis and gastrodermis, attenuation of the epidermal and gastrodermal tissues, presence of cellular debris, and changes in number of zooxanthellae. These findings corroborate results of laboratory-based, sand-application experiments. In addition to the above-noted changes, one specimen exhibited multiple lesions consisting of unusual gastrodermal detachment with infiltration of amoebocytes into the adjacent mesoglea. Tissues surrounding detachment injuries exhibited marked to severe cellular changes. Accumulations of amoebocytes at lesion sites are seldom observed in wild corals. This response may be part of an organized reaction to injury and infection, as has been documented in sea anemones and gorgonians; however, further research is needed on the nature and role(s) of the scleractinian amoebocytes.


Subject(s)
Anthozoa/ultrastructure , Geologic Sediments , Temperature , Animals , Florida
10.
Rev Biol Trop ; 53 Suppl 1: 175-84, 2005 May.
Article in English | MEDLINE | ID: mdl-17465157

ABSTRACT

The Atlantic coast of Broward County, Florida (USA) is paralleled by a series of progressively deeper, shore-parallel coral reef communities. Two of these reef systems are drowned early Holocene coral reefs of 5 ky and 7 ky uncorrected radiocarbon age. Despite the case of access to these reefs, and their major contribution to the local economy, accurate benthic habitat maps of the area are not available. Ecological studies have shown that different benthic communities (i.e. communities composed of different biological taxa) exist along several spatial gradients on all reefs. Since these studies are limited by time and spatial extent, acoustic surveys with the QTCView V bottom classification system based on a 50 kHz transducer were used as an alternative method of producing habitat maps. From the acoustic data of a 3.1 km(2) survey area, spatial prediction maps were created for the area. These were compared with habitat maps interpreted from in situ data and Laser Airborne Depth Sounder (LADS) bathymetry, in order to ground-truth the remotely sensed data. An error matrix was used to quantitatively determine the accuracy of the acoustically derived spatial prediction model against the maps derived from the in situ and LADS data sets. Confusion analysis of 100 random points showed that the system was able to distinguish areas of reef from areas of rubble and sand with an overall accuracy of 61%. When asked to detect more subtle spatial differences, for example, those between distinct reef communities, the classification was only about 40% accurate. We discuss to what degree a synthesis of acoustic and in situ techniques can provide accurate habitat maps in coral reef environments, and conclude that acoustic methods were able to reflect the spatial extent and composition of at least three different biological communities.


Subject(s)
Acoustics , Anthozoa/growth & development , Ecosystem , Environmental Monitoring/standards , Seawater , Animals , Atlantic Ocean , Biodiversity , Cluster Analysis , Environmental Monitoring/methods , Florida , Geography , Image Enhancement , Population Density , Population Dynamics , Principal Component Analysis , Transducers
11.
Blood ; 105(9): 3420-7, 2005 May 01.
Article in English | MEDLINE | ID: mdl-15572587

ABSTRACT

The Cancer and Leukemia Group B (CALGB) study 9222 tested the hypothesis that treatment intensification of acute myeloid leukemia (AML) in first remission with multiple chemotherapy agents is superior to high-dose cytarabine (HiDAC) alone. We enrolled 474 patients younger than 60 years old with untreated de novo AML. Daunorubicin and cytarabine resulted in complete remission (CR) in 342 patients (72%), and 309 of these patients were randomized to receive one of 2 different intensification regimens. The first regimen consisted of 3 courses of HiDAC. The second regimen consisted of one course of HiDAC, a second course with etoposide and cyclophosphamide, and a third course with diaziquone and mitoxantrone. After a median follow-up time of 8.3 years, the median survival for all randomized patients was 2.8 years (95% CI, 1.9-6.8 years). There was no difference in disease-free survival (DFS) between the 2 regimens (P = .66). The median DFS was 1.1 years (95% CI, 0.9-1.7 years) for patients receiving HiDAC and 1.0 year (95% CI, 0.9-1.3 years) for those receiving multiagent chemotherapy. Cytogenetics was the only pretreatment characteristic prognostic for DFS, but there was no evidence of a differential treatment effect within cytogenetic risk groups. Toxicity was greater with multiagent chemotherapy. These 2 postremission regimens produced similar outcomes.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cytarabine/administration & dosage , Leukemia, Myeloid/drug therapy , Acute Disease , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/toxicity , Cytarabine/toxicity , Cytogenetic Analysis , Disease-Free Survival , Female , Follow-Up Studies , Humans , Leukemia, Myeloid/classification , Leukemia, Myeloid/mortality , Male , Middle Aged , Prognosis , Remission Induction/methods , Survival Analysis
12.
J Clin Oncol ; 22(21): 4290-301, 2004 Nov 01.
Article in English | MEDLINE | ID: mdl-15514371

ABSTRACT

PURPOSE: P-glycoprotein (Pgp) is strongly inhibited by PSC-833. A chemotherapy dose-escalation study was performed with PSC-833 in patients younger than 60 years with untreated acute myeloid leukemia. Clinical rather than pharmacokinetic end points were used to develop two induction therapies containing drugs susceptible to Pgp-mediated efflux and associated with comparable toxicities at the maximum-tolerated doses. PATIENTS AND METHODS: A total of 410 patients were enrolled. Fifteen induction regimens containing variable doses of daunorubicin (DNR) and etoposide (ETOP) and fixed doses of cytarabine were evaluated with (ADEP) or without (ADE) a fixed dose of PSC-833. RESULTS: Doses selected for phase III testing were DNR 90 mg/m(2) and ETOP 100 mg/m(2) in ADE, and DNR and ETOP each 40 mg/m(2) in ADEP. Intolerable mucosal toxicity occurred at higher doses of ADEP. Although the design of this study precludes direct comparisons, there was an apparent advantage for receiving ADEP with respect to disease-free and overall survival in patients < or = 45 years old, despite the significantly lower doses of DNR and ETOP given in ADEP compared with ADE. CONCLUSION: A large clinical data set was used to develop induction regimens containing two drugs susceptible to Pgp-mediated efflux, with and without an inhibitor of Pgp function. The chosen doses have comparable antileukemia activity and toxicity, making them suitable for use in a phase III comparative study of induction chemotherapy for patients with acute myeloid leukemia younger than 60 years. That trial will also clarify whether patients < or = 45 years old are especially likely to benefit from Pgp inhibition during induction therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Leukemia, Myeloid/drug therapy , Acute Disease , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclosporins/administration & dosage , Cyclosporins/adverse effects , Cytarabine/administration & dosage , Cytarabine/adverse effects , Daunorubicin/administration & dosage , Daunorubicin/adverse effects , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Humans , Logistic Models , Male , Middle Aged , Survival Analysis , Treatment Outcome
13.
Blood ; 103(11): 4036-42, 2004 Jun 01.
Article in English | MEDLINE | ID: mdl-14976037

ABSTRACT

Whites have a more favorable prognosis than African Americans for a number of cancers. The relationship between race and outcome is less clear in acute myeloid leukemia (AML). Using data from 7 Cancer and Leukemia Group B studies initiated from 1985 to 1997, we conducted a retrospective cross-sectional analysis of 2570 patients (270 African American and 2300 white) with de novo AML who received induction chemotherapy. African Americans were younger than whites (48 versus 54 years, P <.001). African Americans also had different cytogenetic risk group distributions than whites (P <.001): they were more commonly classified in the favorable (23% versus 14%) and unfavorable (31% versus 23%) groups, and less commonly classified in the intermediate group (47% versus 63%). African American men had a lower complete remission (CR) rate (54%, compared with 64% for white men, 65% for white women, and 70% for African American women, P =.001) and a worse overall survival compared with all other patients (P =.004), when known risk factors are taken into account. African Americans and whites with AML differ with respect to important prognostic factors. African American men have worse CR rates and overall survival than whites and African American women, and should be considered a poor-risk group.


Subject(s)
Black or African American , Leukemia, Myeloid/ethnology , Leukemia, Myeloid/therapy , White People , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Leukemia, Myeloid/mortality , Male , Middle Aged , Prognosis , Remission Induction , Retrospective Studies , Risk Factors , Treatment Outcome
14.
Lancet ; 363(9408): 535-6, 2004 Feb 14.
Article in English | MEDLINE | ID: mdl-14975618

ABSTRACT

The activation of oncogenic transcription factors defines distinct molecular subsets of T-cell acute lymphoblastic leukaemia and has prognostic relevance in children. We investigated the prognostic effect of the expression levels of eight oncogenic transcription factors--TLX1 (HOX11), TLX3 (HOX11L2), TAL1, TAL2, LYL1, OLIG2 (BHLHB1), LMO1, and LMO2--in 52 adults with T-cell acute lymphoblastic leukaemia. The leukaemia-specific survival rate for the 16 TLX1-positive patients was 88% (90% CI 73-100%), compared with 56% (42-70%) for all other cases (p=0.019). Only the TLX1 oncogene expression subgroup showed difference in leukaemia-specific survival. Our results suggest that overexpression of TLX1 confers a good outlook for adults with T-cell acute lymphoblastic leukaemia. Furthermore, our findings lead to questions about whether stem-cell transplantation in first remission is necessary for effective treatment of patients in the low-risk subgroup of patients with TLX1 oncogene expression.


Subject(s)
Gene Expression Regulation, Leukemic/genetics , Homeodomain Proteins/genetics , Leukemia-Lymphoma, Adult T-Cell/genetics , Leukemia-Lymphoma, Adult T-Cell/metabolism , Oncogene Proteins/genetics , Adaptor Proteins, Signal Transducing , Adult , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Gene Expression Profiling , Homeodomain Proteins/metabolism , Humans , LIM Domain Proteins , Leukemia-Lymphoma, Adult T-Cell/mortality , Metalloproteins/genetics , Metalloproteins/metabolism , Oncogene Proteins/metabolism , Prognosis , Proto-Oncogene Proteins , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate , Transcription Factors/genetics , Transcription Factors/metabolism
15.
Br J Haematol ; 124(3): 275-88, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14717774

ABSTRACT

We analysed the nature and prognostic significance of secondary cytogenetic changes in 111 newly diagnosed adults with acute lymphoblastic leukaemia (ALL) and t(9;22)(q34;q11.2) or its variants. Secondary aberrations were seen in 75 (68%) patients. They included, in order of descending frequency: +der(22)t(9;22), +21, abnormalities of 9p, high hyperdiploidy (>50 chromosomes), +8, -7, +X and abnormalities resulting in loss of material from 8p, gain of 8q, gain of 1q and loss of 7p. Eighty patients (72%) had > or =1 normal metaphase in their karyotype. There were four balanced and 12 unbalanced translocations previously unreported in ALL with t(9;22). The t(2;7)(p11;p13) and der(18)t(8;18)(q11.2;p11.2) were seen in two cases each, and have never before been reported in haematological malignancy. All but four patients were treated on front-line Cancer and Leukaemia Group B clinical protocols. The presence of -7 as a sole secondary abnormality was associated with a lower complete remission (CR) rate (P = 0.004), while the presence of > or =3 aberrations was associated with a higher CR rate (P = 0.009) and +der(22)t(9;22) with a higher cumulative incidence of relapse (P = 0.02). It will be of interest to see if newly diagnosed t(9;22)-positive adult ALL patients with these and other secondary aberrations respond differently to treatment regimens that include imatinib mesylate.


Subject(s)
Chromosome Aberrations , Chromosomes, Human, Pair 22 , Chromosomes, Human, Pair 9 , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adult , Aged , Antineoplastic Agents/therapeutic use , Benzamides , Chromosomes, Human, Pair 2 , Chromosomes, Human, Pair 7 , Female , Humans , Imatinib Mesylate , Karyotyping , Male , Middle Aged , Piperazines/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prognosis , Prospective Studies , Pyrimidines/therapeutic use , Recurrence , Remission Induction , Translocation, Genetic
16.
J Am Vet Med Assoc ; 223(6): 825-31, 2003 Sep 15.
Article in English | MEDLINE | ID: mdl-14507100

ABSTRACT

OBJECTIVE: To characterize the signalment, clinical signs, biological behavior, and response to treatment of carcinoma of the apocrine glands of the anal sac in dogs. DESIGN: Retrospective study. ANIMALS: 113 dogs with histologically confirmed carcinoma of the apocrine glands of the anal sac. PROCEDURE: Data on signalment, clinical signs, and staging were reviewed and analyzed along with treatment modality for potential association with survival time. RESULTS: Sex distribution was approximately equal (54% female, 46% male). One hundred four dogs underwent treatment consisting of surgery, radiation therapy, chemotherapy, or multimodal treatment. Median survival for treated dogs was 544 days (range, 0 to 1,873 days). Dogs treated with chemotherapy alone had significantly shorter survival (median, 212 days) than those receiving other treatments (median, 584 days). Dogs not treated with surgery had significantly shorter survival (median, 402 days) than those that underwent surgery as part of their treatment (median, 548 days). Dogs with tumors > or = 10 cm2 had significantly shorter survival (median, 292 days) than dogs with tumors < 10 cm2 (median, 584 days). Hypercalcemia was identified in 27% (n = 29) of dogs, and those dogs had significantly shorter survival (median, 256 days), compared with those that were normocalcemic (median, 584 days). Dogs with pulmonary metastasis had significantly shorter survival (median, 219 days) than dogs without evidence of pulmonary metastasis (median, 548 days). CONCLUSIONS AND CLINICAL RELEVANCE: Unlike most previous reports, this study revealed an approximately equal sex distribution, and results suggest a more favorable prognosis.


Subject(s)
Anal Gland Neoplasms/epidemiology , Carcinoma/veterinary , Dog Diseases/epidemiology , Anal Gland Neoplasms/surgery , Anal Gland Neoplasms/therapy , Anal Sacs/pathology , Animals , Apocrine Glands/pathology , Carcinoma/epidemiology , Carcinoma/therapy , Combined Modality Therapy/veterinary , Dog Diseases/surgery , Dog Diseases/therapy , Dogs , Female , Lung Neoplasms/mortality , Lung Neoplasms/secondary , Lung Neoplasms/veterinary , Male , Retrospective Studies , Sex Distribution , Survival Analysis , Treatment Outcome
17.
Vet Radiol Ultrasound ; 44(3): 352-9, 2003.
Article in English | MEDLINE | ID: mdl-12816381

ABSTRACT

Despite the early notion that canine oral malignant melanoma is radioresistant, recent data suggest that external beam radiotherapy is effective in local tumor control. However, optimal fractionation schedules have not been established. The high rate of regional and distant metastasis is another problem that has hindered long-term control. The role of chemotherapy in the management of canine oral melanoma has also not been determined. In this study, data from 140 dogs irradiated at North Carolina State University were evaluated with the following objectives: (1) to compare the efficacy of three radiation therapy protocols (36 Gy, 9 Gy x 4 fractions; 30 Gy, 10 Gy x 3 fractions; or >45 Gy, 2-4 Gy x 12-19 fractions) for the treatment of dogs with oral malignant melanoma, (2) to identify any host or tumor factors influencing prognosis, and (3) to determine the impact of systemic chemotherapy on treatment outcome. Information regarding response to therapy, disease progression, and survival were determined from the medical records or from information obtained by telephone or mail survey. Relationships between host, tumor, and treatment variables and outcome measures (response, time to first event, and survival) were evaluated using Fisher's exact test (response) and the Cox regression model (time to first event and survival). The median time to first event for the 140 dogs was 5.0 months (95% C.I., 4-6 months) and the median survival was 7.0 months (95% C.I., 6-9 months). In the univariate analysis, the following variables were associated with increased time to first event and survival: (1) rostral tumor sublocation; (2) lack of bone lysis observed on skull imaging, and (3) microscopic tumor burden. In a multivariate analysis of 111 dogs with complete data for these variables, tumor sublocation, bone lysis, and tumor volume were identified as joint predictors of time to first event (p < .001, p < .001, and p = .04, respectively) and survival (p < .001, p < .001, and p = .05, respectively). There were no differences in response, time to first event and survival between the three radiation therapy protocols used. Systemic chemotherapy had no impact on the development of metastatic disease, time to first event, or survival, although the dosages used in this study were suboptimal. External beam radiation therapy is effective in local disease control of canine oral malignant melanoma; however, the optimal fractionation scheme has yet to be determined. The high metastatic rate observed with this disease and the inefficacy of systemic chemotherapy indicate that further investigation into novel therapies is warranted.


Subject(s)
Dog Diseases/mortality , Melanoma/veterinary , Mouth Neoplasms/veterinary , Neoplasm Recurrence, Local/veterinary , Animals , Disease-Free Survival , Dog Diseases/radiotherapy , Dogs , Dose Fractionation, Radiation , Female , Male , Melanoma/mortality , Mouth Neoplasms/mortality , Neoplasm Recurrence, Local/mortality , North Carolina/epidemiology , Records/veterinary , Retrospective Studies , Survival Analysis , Treatment Outcome
18.
Biol Blood Marrow Transplant ; 9(3): 183-8, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12652469

ABSTRACT

We have performed a phase I dose escalation of 4-Hydroperoxycyclophosphamide (4HC) purging of autologous peripheral blood progenitor cells (PBPCs) to improve the outcome of autologous transplantation for patients with myeloid leukemia. Peripheral blood stem cells were mobilized after cytosine arabinoside of 2 g/m(2) every 12 hours x 8 doses with etoposide of 40 mg/kg total dose infused over 4 days, followed by growth factor support. The preparative regimen included Busulfan of 1 mg/kg orally every 6 hours x 16 doses, followed by etoposide of 60 mg/kg x 1 day (the patient with chronic myeloid leukemia received cyclophosphamide of 60 mg/kg/d x 2 days in lieu of etoposide). PBPCs purged with 4HC were infused following this induction. Toxicities included grade 3 or 4 skin rashes, stomatitis/mucositis, and delay in time to hematopoietic recovery. The maximum tolerated dose of 4HC used to purge PBPCs in this trial was 20 microg/mL, which resulted in an average of 18 days for white blood cells and 28 days for platelet recovery. With a median follow-up of 2.25 years in surviving patients, the 3-year disease free survival rate is 44% and the overall survival rate is 89%. These data suggest that autologous PBPCs are more sensitive than marrow purged with 4HC, tolerating less intense purging, although a survival advantage may still be seen and should be assessed in larger studies. Approaches to minimize stomatitis and protect normal stem cells from the toxicity of 4HC may improve the tolerance and efficacy of this approach.


Subject(s)
Cyclophosphamide/analogs & derivatives , Cyclophosphamide/administration & dosage , Cyclophosphamide/toxicity , Leukemia, Myeloid/therapy , Neoplastic Cells, Circulating/drug effects , Peripheral Blood Stem Cell Transplantation/methods , Acute Disease , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Female , Hematopoiesis , Hematopoietic Stem Cell Mobilization/methods , Humans , Leukemia, Myeloid/mortality , Leukocytes, Mononuclear/drug effects , Male , Maximum Tolerated Dose , Middle Aged , Peripheral Blood Stem Cell Transplantation/mortality , Remission Induction/methods , Survival Analysis , Transplantation, Autologous
19.
Cancer ; 97(6): 1471-80, 2003 Mar 15.
Article in English | MEDLINE | ID: mdl-12627512

ABSTRACT

BACKGROUND: Anti-B4-blocked ricin is an immunotoxin comprised of an anti-CD19 murine monoclonal antibody (B4) conjugated to blocked ricin, which has cytotoxic activity in patients with lymphoid malignancies. METHODS: Adults with untreated acute lymphoblastic leukemia (ALL) were treated with a previously developed and tested chemotherapeutic regimen. Patients with CD19 positive ALL were given anti-B4-blocked ricin as 2 7-day continuous infusions 1 week apart. Patients with CD19 negative ALL received high-dose cytarabine. Serial polymerase chain reaction (PCR) assays of BCR-ABL, immunoglobulin heavy chain (IGH), and T-cell receptor (TCR) genes were used to measure the impact of lineage specific intensification treatment on minimal residual disease. RESULTS: Eighty-two adults were enrolled, and 78 were eligible. The median age was 34 years (range, 17-81 years). Sixty-six patients (85%) achieved complete remission. Forty-six patients received the anti-B4-blocked ricin, which generally was well tolerated; 80% were able to receive both courses. The most common toxicity was asymptomatic transient elevation of liver function tests in 72% of patients. Lymphopenia occurred in 46% of patients. Two patients developed antibodies to the anti-B4-blocked ricin. Molecular monitoring before and after the experimental course of intensification did not show a consistent change in the number of leukemia cells remaining, and the immediate posttreatment PCR studies did not correlate with remission duration. CONCLUSIONS: Intensification therapy with anti-B4-blocked ricin is feasible for patients with CD19 positive ALL, although there is little evidence of an additional clinical benefit from the anti-B4-blocked ricin. Cancer 2003;97:1471-80.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Cytarabine/pharmacology , Immunoconjugates/pharmacology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Ricin/pharmacology , Adolescent , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Cytarabine/administration & dosage , Female , Genes, abl , Humans , Immunoconjugates/administration & dosage , Infusions, Intravenous , Male , Middle Aged , Polymerase Chain Reaction , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Receptors, Antigen, T-Cell/analysis , Ricin/administration & dosage , Treatment Outcome
20.
Obstet Gynecol ; 101(1): 157-63, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12517661

ABSTRACT

To identify patients who fail intermittent pneumatic compression and who might be considered for other more intense thromboembolic prophylaxis.We conducted a retrospective review of consecutive gynecologic surgery patients treated with intermittent pneumatic compression. Risk factors associated with thromboemboli and demographic data were reviewed. Clinical suspicion of thromboemboli was confirmed by established diagnostic techniques such as duplex Doppler ultrasound and ventilation perfusion scanning. The association between individual risk factors and the incidence of thromboemboli was identified. To control for confounding of variables, multivariable stepwise logistic regression analysis was performed.A total of 1862 patients undergoing gynecologic surgery between 1996 and 1997 were treated perioperatively with intermittent pneumatic compression. The overall incidence of postoperative thromboemboli was 1.3% (15 cases of clinically significant postoperative pulmonary emboli and nine deep venous thrombosis). Risk factors associated with the occurrence of thromboemboli were: cancer (P =.001), history of deep venous thrombosis (P =.03), hypertension (P =.05), use of antihypertensives (P =.04), and age at least 60 years (P =.002). Intraoperative risk factors included duration of anesthesia more than 3 hours (P =.05). The multivariable regression analysis found that the diagnosis of cancer (P =.001), history of deep venous thrombosis (P =.006), and age greater than 60 years (P =.04) were independent prognostic factors. Patients with two or three of these variables had a 3.2% incidence of developing thromboemboli as compared with a 0.6% incidence of thromboemboli if the patient had none or one risk factor. Patients most likely to fail intermittent pneumatic compression prophylaxis include those with cancer, a past history of deep venous thrombosis, or who are 60 years or older. This information identifies a "higher-risk" group of patients who should be considered for more intense prophylaxis programs.


Subject(s)
Embolism/prevention & control , Gynecologic Surgical Procedures , Postoperative Complications/prevention & control , Venous Thrombosis/prevention & control , Adult , Aged , Embolism/diagnosis , Female , Humans , Logistic Models , Middle Aged , Pressure , Retrospective Studies , Risk Assessment , Venous Thrombosis/diagnosis
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