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1.
Environ Res ; 249: 118346, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38311204

ABSTRACT

Quantitative next-generation sequencing techniques have been critical in gaining a better understanding of microbial ecosystems. In soils, denitrifying microorganisms are responsible for dinitrogen (N2) production. The nosZ gene codes for nitrous oxide reductase, the enzyme facilitating the reduction of nitrous oxide (N2O) to N2. The objectives of this research were to: 1) understand how soil depth influences RNA concentration and nosZ gene abundance; 2) assess the spatial dependence of nosZ gene abundance in two claypan soil fields; and 3) compare and evaluate multiple RNA-based sequencing methods for quantifying nosZ gene abundance in soils in relation to dinitrogen (N2) production. Research sites consisted of two intensively studied claypan soil fields in Central Missouri, USA. Soil cores were collected from two landscape transects across both fields and analyzed for extractable soil RNA at two depths (0-15 cm and 15-30 cm). Measurements of nosZ gene abundance were obtained using real-time quantitative polymerase chain reaction (RT-qPCR), droplet digital polymerase chain reaction (ddPCR), and nanostring sequencing (NS). In both fields, soil RNA concentrations were significantly greater at 0-15 cm depth compared to 15-30 cm. These data indicated low overall soil microbial activity below 15 cm. Due to low quantities of extractable soil RNA in the subsoil, nosZ gene abundance was only determined in the 0-15 cm depth. Sequencing method comparisons of average nosZ gene abundance showed that NS results were constrained to a narrow range and were 10-20-fold lower than ddPCR and RT-qPCR at each landscape position within each field. Droplet digital PCR appears to be the most promising method, as it reflected changes in N2 production across landscape position.


Subject(s)
High-Throughput Nucleotide Sequencing , Soil Microbiology , Soil , High-Throughput Nucleotide Sequencing/methods , Missouri , Oxidoreductases/genetics , Soil/chemistry
2.
J Cell Physiol ; 233(4): 2681-2692, 2018 04.
Article in English | MEDLINE | ID: mdl-28833090

ABSTRACT

CRSBP-1 (mammalian LYVE-1) is a membrane glycoprotein highly expressed in lymphatic endothelial cells (LECs). It has multiple ligands, including hyaluronic acid (HA) and growth factors/cytokines (e.g., PDGF-BB and VEGF-A) containing CRS motifs (clusters of basic amino-acid residues). The ligand binding activities are mediated by Link module and acidic-amino-acid-rich (AAAR) domains, respectively. These CRSBP-1/LYVE-1 ligands have been shown to induce opening of lymphatic intercellular junctions in LEC monolayers and in lymphatic vessels in wild-type mice. We hypothesize that CRSBP-1/LYVE-1 ligands, particularly CRS-containing growth factors/cytokines, are secreted by immune and cancer cells for lymphatic entry during adaptive immune responses and lymphatic metastasis. We have looked into the origin of the Link module and AAAR domain of LYVE-1 in evolution and its association with the development of lymph nodes and efficient adaptive immunity. Lymph nodes represent the only major recent innovation of the adaptive immune systems in evolution particularly to mammals and bird. Here we demonstrate that the development of the LYVE-1 gene with the AAAR domain in evolution is associated with acquisition of lymph nodes and adaptive immunity. LYVE-1 from other species, which have no lymph nodes, lack the AAAR domain and efficient adaptive immunity. Synthetic CRSBP-1 ligands PDGF and VEGF peptides, which contain the CRS motifs of PDGF-BB and VEGF-A, respectively, specifically bind to CRSBP-1 but do not interact with either PDGFßR or VEGFR2. These peptides function as adjuvants by enhancing adaptive immunity of pseudorabies virus (PRV) vaccine in pigs. These results support the notion that LYVE-1 is involved in adaptive immunity in mammals.


Subject(s)
Adaptive Immunity , Amino Acids, Acidic/metabolism , Evolution, Molecular , Lymph Nodes/immunology , Membrane Proteins/chemistry , Membrane Proteins/genetics , Adaptive Immunity/drug effects , Adjuvants, Immunologic/pharmacology , Amino Acid Sequence , Animals , Base Sequence , Female , Ligands , Lymph Nodes/drug effects , Membrane Proteins/metabolism , Peptides/pharmacology , Phylogeny , Platelet-Derived Growth Factor/pharmacology , Protein Domains , Pseudorabies Vaccines/immunology , Sequence Alignment , Sharks , Structural Homology, Protein , Structure-Activity Relationship , Sus scrofa , Vascular Endothelial Growth Factor A/pharmacology , Zebrafish
3.
J Cell Biochem ; 118(6): 1387-1400, 2017 06.
Article in English | MEDLINE | ID: mdl-27862220

ABSTRACT

For several decades, cholesterol has been thought to cause ASCVD. Limiting dietary cholesterol intake has been recommended to reduce the risk of the disease. However, several recent epidemiological studies do not support a relationship between dietary cholesterol and/or blood cholesterol and ASCVD. Consequently, the role of cholesterol in atherogenesis is now uncertain. Much evidence indicates that TGF-ß, an anti-inflammatory cytokine, protects against ASCVD and that suppression of canonical TGF-ß signaling (Smad2-dependent) is involved in atherogenesis. We had hypothesized that cholesterol causes ASCVD by suppressing canonical TGF-ß signaling in vascular endothelium. To test this hypothesis, we determine the effects of cholesterol, 7-dehydrocholesterol (7-DHC; the biosynthetic precursor of cholesterol), and other sterols on canonical TGF-ß signaling. We use Mv1Lu cells (a model cell system for studying TGF-ß activity) stably expressing the Smad2-dependent luciferase reporter gene. We demonstrate that 7-DHC (but not cholesterol or other sterols) effectively suppresses the TGF-ß-stimulated luciferase activity. We also demonstrate that 7-DHC suppresses TGF-ß-stimulated luciferase activity by promoting lipid raft/caveolae formation and subsequently recruiting cell-surface TGF-ß receptors from non-lipid raft microdomains to lipid rafts/caveolae where TGF-ß receptors become inactive in transducing canonical signaling and undergo rapid degradation upon TGF-ß binding. We determine this by cell-surface 125 I-TGF-ß-cross-linking and sucrose density gradient ultracentrifugation. We further demonstrate that methyl-ß-cyclodextrin (MßCD), a sterol-chelating agent, reverses 7-DHC-induced suppression of TGF-ß-stimulated luciferase activity by extrusion of 7-DHC from resident lipid rafts/caveolae. These results suggest that 7-DHC, but not cholesterol, promotes lipid raft/caveolae formation, leading to suppression of canonical TGF-ß signaling and atherogenesis. J. Cell. Biochem. 118: 1387-1400, 2017. © 2016 Wiley Periodicals, Inc.


Subject(s)
Atherosclerosis/metabolism , Cholesterol/pharmacology , Dehydrocholesterols/pharmacology , Transforming Growth Factor beta/metabolism , Caveolae/metabolism , Cell Line , Humans , Membrane Microdomains/metabolism , Receptors, Transforming Growth Factor beta/metabolism , Signal Transduction/drug effects , Smad2 Protein/metabolism
4.
J Cell Biochem ; 117(4): 860-71, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26419316

ABSTRACT

Regular consumption of moderate amounts of ethanol has important health benefits on atherosclerotic cardiovascular disease (ASCVD). Overindulgence can cause many diseases, particularly alcoholic liver disease (ALD). The mechanisms by which ethanol causes both beneficial and harmful effects on human health are poorly understood. Here we demonstrate that ethanol enhances TGF-ß-stimulated luciferase activity with a maximum of 0.5-1% (v/v) in Mv1Lu cells stably expressing a luciferase reporter gene containing Smad2-dependent elements. In Mv1Lu cells, 0.5% ethanol increases the level of P-Smad2, a canonical TGF-ß signaling sensor, by ∼ 2-3-fold. Ethanol (0.5%) increases cell-surface expression of the type II TGF-ß receptor (TßR-II) by ∼ 2-3-fold from its intracellular pool, as determined by I(125) -TGF-ß-cross-linking/Western blot analysis. Sucrose density gradient ultracentrifugation and indirect immunofluorescence staining analyses reveal that ethanol (0.5% and 1%) also displaces cell-surface TßR-I and TßR-II from lipid rafts/caveolae and facilitates translocation of these receptors to non-lipid raft microdomains where canonical signaling occurs. These results suggest that ethanol enhances canonical TGF-ß signaling by increasing non-lipid raft microdomain localization of the TGF-ß receptors. Since TGF-ß plays a protective role in ASCVD but can also cause ALD, the TGF-ß enhancer activity of ethanol at low and high doses appears to be responsible for both beneficial and harmful effects. Ethanol also disrupts the location of lipid raft/caveolae of other membrane proteins (e.g., neurotransmitter, growth factor/cytokine, and G protein-coupled receptors) which utilize lipid rafts/caveolae as signaling platforms. Displacement of these membrane proteins induced by ethanol may result in a variety of pathologies in nerve, heart and other tissues.


Subject(s)
Caveolae/drug effects , Cytoplasmic Vesicles/drug effects , Epithelial Cells/drug effects , Ethanol/pharmacology , Receptors, Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/genetics , Animals , Caveolae/chemistry , Caveolae/metabolism , Caveolin 1/genetics , Caveolin 1/metabolism , Cell Fractionation , Cell Line, Transformed , Cytoplasmic Vesicles/chemistry , Cytoplasmic Vesicles/metabolism , Dose-Response Relationship, Drug , Epithelial Cells/cytology , Epithelial Cells/metabolism , Gene Expression Regulation , Genes, Reporter , Luciferases/genetics , Luciferases/metabolism , Lung/cytology , Lung/drug effects , Lung/metabolism , Membrane Microdomains/chemistry , Membrane Microdomains/drug effects , Membrane Microdomains/metabolism , Mink , Phosphorylation , Protein Isoforms/genetics , Protein Isoforms/metabolism , Receptors, Transforming Growth Factor beta/metabolism , Signal Transduction , Smad2 Protein/genetics , Smad2 Protein/metabolism , Transforming Growth Factor beta/metabolism
5.
Ann Surg Oncol ; 21(3): 733-7, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24046113

ABSTRACT

The incidence of breast cancer has been on the rise in the United States over the past several decades. The advanced longevity of the population during this same time period, specifically of elderly women, translates to increases in the absolute number of women diagnosed with breast cancer yearly. This, in combination with decreasing mortality rates, has now led to an increase in the number of breast cancer survivors who need long-term follow-up. There has been significant debate over what tests should be obtained, how often they should be obtained, how long surveillance should be continued, and by whom this should be performed. We review the published guidelines for surveillance, available data regarding low- versus high-intensity surveillance plans, current practice patterns, and recommendations for future strategies.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Continuity of Patient Care , Diagnostic Tests, Routine/statistics & numerical data , Diagnostic Tests, Routine/trends , Female , Follow-Up Studies , Humans , Population Surveillance , Prognosis , Survival Rate , Survivors
6.
J Environ Qual ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816346

ABSTRACT

The Lower Mississippi River Basin-Long-Term Agroecosystem Research Site (LMRB-LTAR) encompasses six states from Missouri to the Gulf of Mexico and is coordinated by the USDA-ARS National Sedimentation Laboratory, Oxford, MS. The overarching goal of LTAR is to assess regionally diverse and geographically scalable farming practices for enhanced sustainability of agroecosystem goods and services under changing environment and resource-use conditions. The LMRB-LTAR overall goal is to assess sustainable row crop agricultural production systems that integrate regional environmental and socioeconomic needs. Primary row crops in the region include soybeans, corn, cotton, rice, and sugarcane with crop rotations influenced by commodity crop price and other factors. The field-scale common experiment (CE) includes four row crop farms (26-101 ha) established in 2021 and 2023. Three fields are managed with alternative practices, including reduced tillage, cover crops, and automated prescription irrigation, and three fields are managed with prevailing farming practices, consisting of conventional tillage, no cover crop, and nonprescription irrigation. Treatment effects on crop productivity, soil quality, water use efficiency, water quality, and carbon storage are assessed. Research from the LMRB CE will deliver outcomes linked to overarching LTAR network goals, including innovative agricultural systems, strengthened partnerships, data management technologies, and precision environmental tools.

7.
J Cell Sci ; 124(Pt 8): 1231-44, 2011 Apr 15.
Article in English | MEDLINE | ID: mdl-21444752

ABSTRACT

Cell-surface retention sequence (CRS) binding protein (CRSBP-1) is a membrane glycoprotein identified by its ability to bind PDGF-BB and VEGF-A via their CRS motifs (clusters of basic amino acid residues). CRSBP-1 is identical to LYVE-1 and exhibits dual ligand (CRS-containing proteins and hyaluronic acid) binding activity, suggesting the importance of CRSBP-1 ligands in lymphatic function. Here, we show that CRSBP-1 ligands induce disruption of VE-cadherin-mediated intercellular adhesion and opening of intercellular junctions in lymphatic endothelial cell (LEC) monolayers as determined by immunofluorescence microscopy and Transwell permeability assay. This occurs by interaction with CRSBP-1 in the CRSBP-1-PDGFßR-ß-catenin complex, resulting in tyrosine phosphorylation of the complex, dissociation of ß-catenin and p120-catenin from VE-cadherin, and internalization of VE-cadherin. Pretreatment of LECs with a PDGFßR kinase inhibitor abolishes ligand-stimulated tyrosine phosphorylation of VE-cadherin, halts the ligand-induced disruption of VE-cadherin intercellular adhesion and blocks the ligand-induced opening of intercellular junctions. These CRSBP-1 ligands also induce opening of lymphatic intercellular junctions that respond to PDGFßR kinase inhibitor in wild-type mice (but not in Crsbp1-null mice) as evidenced by increased transit of injected FITC-dextran and induced edema fluid from the interstitial space into lymphatic vessels. These results disclose a novel mechanism involved in the opening of lymphatic intercellular junctions.


Subject(s)
Antigens, CD/metabolism , Cadherins/metabolism , Endothelial Cells/physiology , Membrane Proteins/metabolism , Tyrosine/metabolism , Animals , Antigens, CD/genetics , Cadherins/genetics , Cell Adhesion , Cell Line , Hyaluronic Acid/metabolism , Ligands , Membrane Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Phosphorylation , Protein Binding , Receptor, Platelet-Derived Growth Factor beta/genetics , Receptor, Platelet-Derived Growth Factor beta/metabolism , beta Catenin/genetics , beta Catenin/metabolism
8.
Microb Ecol ; 65(4): 1024-38, 2013 May.
Article in English | MEDLINE | ID: mdl-23508733

ABSTRACT

In May of 2011, a live mass stranding of 26 short-finned pilot whales (Globicephala macrorhynchus) occurred in the lower Florida Keys. Five surviving whales were transferred from the original stranding site to a nearby marine mammal rehabilitation facility where they were constantly attended to by a team of volunteers. Bacteria cultured during the routine clinical care of the whales and necropsy of a deceased whale included methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). In order to investigate potential sources or reservoirs of MSSA and MRSA, samples were obtained from human volunteers, whales, seawater, and sand from multiple sites at the facility, nearby recreational beaches, and a canal. Samples were collected on 3 days. The second collection day was 2 weeks after the first, and the third collection day was 2 months after the last animal was removed from the facility. MRSA and MSSA were isolated on each day from the facility when animals and volunteers were present. MSSA was found at an adjacent beach on all three collection days. Isolates were characterized by utilizing a combination of quantitative real-time PCR to determine the presence of mecA and genes associated with virulence, staphylococcal protein A typing, staphylococcal cassette chromosome mec typing, multilocus sequence typing, and pulsed field gel electrophoresis (PFGE). Using these methods, clonally related MRSA were isolated from multiple environmental locations as well as from humans and animals. Non-identical but genetically similar MSSA and MRSA were also identified from distinct sources within this sample pool. PFGE indicated that the majority of MRSA isolates were clonally related to the prototype human strain USA300. These studies support the notion that S. aureus may be shed into an environment by humans or pilot whales and subsequently colonize or infect exposed new hosts.


Subject(s)
Cetacea/microbiology , Fin Whale/microbiology , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/microbiology , Staphylococcal Infections/veterinary , Animals , Anti-Bacterial Agents/pharmacology , Florida , Humans , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/genetics , Volunteers
9.
J Spinal Cord Med ; 36(3): 207-12, 2013 May.
Article in English | MEDLINE | ID: mdl-23809590

ABSTRACT

OBJECTIVE: Patients with spinal cord injury (SCI) typically have difficulty with constipation. Some undergo surgery for bowel management. We predicted that SCI patients would have higher mortality and/or morbidity rates following such surgery than neurally intact patients receiving the same procedures. We sought to evaluate this using a large population-based data set. METHODS: Patients receiving care at Department of Veterans Affairs Medical Centers (DVAMCs) with computer codes for SCI and constipation who later underwent colectomy, colostomy, or ileostomy during fiscal years 1993-2002 were identified. Charts were requested from the VAMCs where the surgery had been performed and a retrospective chart review of these charts was done. We collected data on patient demographics, six specific pre-operative co-morbidities, surgical complications, and post-operative mortality. Comparisons were made to current literature evaluating a population receiving total abdominal colectomy and ileorectal anastomosis for constipation but not selected for SCI. RESULTS: Of 299 patients identified by computer search, 43 (14%) had codes for SCI and 10 of 43 (24%) met our inclusion criteria. All were symptomatic and had received appropriate medical management. Co-morbid conditions were present in 9 of 10 patients (90%). There were no deaths within 30 days. The complication rate was zero. The mean post-operative length of stay was 17 days. CONCLUSIONS: Patients with SCI comprise about 14% of the population who receive surgery for severe constipation in the Department of Veterans Affairs system. The mortality and morbidity rates in these patients are similar to those reported in other constipated patients who have surgery for intractable constipation. Our data suggest that stoma formation ± bowel resection in patients with SCI is a safe and effective treatment for chronic constipation.


Subject(s)
Constipation/etiology , Constipation/surgery , Digestive System Surgical Procedures/mortality , Spinal Cord Injuries/complications , Constipation/mortality , Humans , Male , Middle Aged , Neurogenic Bowel/etiology , Neurogenic Bowel/mortality , Neurogenic Bowel/surgery , Spinal Cord Injuries/mortality , Veterans
10.
Gynecol Oncol ; 120(2): 205-8, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21075437

ABSTRACT

OBJECTIVE: Patient surveillance after potentially curative treatment of ovarian carcinoma has important clinical and financial implications for patients and society. The optimal intensity of surveillance for these patients is unknown. We aimed to document the current follow-up practice patterns of gynecologic oncologists. METHODS: We created four idealized vignettes describing patients with stages I-III ovarian cancer. We mailed a custom-designed survey instrument based on the vignettes to the members of the Society of Gynecologic Oncologists (SGO). SGO members were asked, via this instrument, how often they requested 11 discrete follow-up evaluations for their patients for the first 10 postoperative years after treatment with curative intent. RESULTS: We received 283 evaluable responses (30%) from the 943 SGO members and candidate members. The most frequently performed items for each year were office visit, pelvic examination, and serum CA-125 level. Imaging studies such as chest X-ray, abdominal-pelvic CT, chest CT, abdominal-pelvic MRI, and transvaginal ultrasound were rarely recommended. There was marked variation in the frequency of use of most tests. There was a decrease in the frequency of testing over time for all modalities. CONCLUSION: This dataset provides detailed documentation of the self-reported surveillance practices of highly credentialed experts who manage patients with ovarian cancer in the 21st century. The optimal follow-up strategy remains unknown and controversial. Our survey showed marked variation in surveillance intensity. Identifying the sources of this variation warrants further research.


Subject(s)
Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Middle Aged , Monitoring, Physiologic/methods , Ovarian Neoplasms/pathology , Postoperative Care/methods , Practice Patterns, Physicians' , Surveys and Questionnaires
11.
Oncol Rep ; 21(6): 1511-7, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19424631

ABSTRACT

Many believe that follow-up testing for rectal carcinoma patients after primary curative-intent therapy should be rather intensive for high-stage lesions and less intensive for low-stage lesions. We recently carried out a survey of the American Society of Colon and Rectal Surgeons (ASCRS) to quantify the strategies they use after primary treatment for their own patients. Considerable variability in surveillance exists. Here we report how initial TNM stage affects follow-up intensity. We devised vignettes succinctly describing otherwise healthy patients with rectal carcinoma (stages I-III). We mailed a questionnaire based on the vignettes to the 1,795 ASCRS members. Responses deemed evaluable were entered into a computer database. The effect of TNM stage on follow-up intensity for patients with stage I, II, or III rectal carcinoma treated with radical surgery was assessed by repeated-measures ANOVA. The surveillance modality most frequently utilized was the office visit. In year 1 following surgery for patients with stage I lesions, 3.8+/-2.7 office visits (mean +/- SD) were recommended, decreasing to 1.5+/-1.0 in year 5. For patients with stage III lesions treated with radical surgery +/- adjuvant therapy, 4.0+/-2.8 office visits were recommended in year 1, decreasing to 1.7+/-1.2 in year 5. Similar results were generated for all commonly used surveillance modalities. The intensity of follow-up after curative-intent treatment for rectal carcinoma varies minimally across TNM stages. This suggests that a controlled trial comparing high-intensity versus low-intensity follow-up testing could be carried out without stratification by TNM stage.


Subject(s)
Carcinoma/pathology , Carcinoma/therapy , Practice Patterns, Physicians'/statistics & numerical data , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Diagnostic Imaging/statistics & numerical data , Diagnostic Techniques, Digestive System/statistics & numerical data , Health Care Surveys , Humans , Neoplasm Staging , Office Visits/statistics & numerical data , Surveys and Questionnaires , Time Factors , Treatment Outcome
12.
Surg Oncol ; 17(4): 313-6, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18625548

ABSTRACT

INTRODUCTION: Limited published information is available concerning the clinical course of spinal cord injured (SCI) patients who later develop rectal cancer and undergo proctectomy. We hypothesized that such patients would have poorer outcomes than comparable neurally-intact patients. METHODS: We conducted a retrospective study of all SCI veterans receiving care at all Department of Veterans Affairs (DVA) Medical Centers who subsequently underwent proctectomy for rectal cancer during fiscal years 1993-2002. Only patients with SCI due to trauma who met American Spinal Injury Association type A criteria (complete cord injury) were analyzed. The search strategy utilized DVA datasets plus data extracted from medical records. RESULTS: There were 33,758 patients with ICD-9-CM diagnosis codes for SCI and 5246 patients with ICD-9-CM procedure codes for proctectomy due to rectal cancer; 72 patients were in both datasets. We received records for 72 patients and excluded 67 after chart review. Incorrect coding (44) and incomplete spinal cord lesions (9) were the most common exclusion criteria. Five patients were considered evaluable. The mean age at diagnosis was 65 (range 49-80). All five had symptomatic cancers and two (40%) had major comorbidities at admission. Postoperative complications occurred in four (80%). The winsorized mean length of stay was 28 days. CONCLUSIONS: The complication rate and length of stay for SCI patients undergoing proctectomy for rectal cancer were higher than those reported for otherwise comparable neurally-intact patients. SCI should be considered a risk factor for adverse outcomes in operations for rectal cancer as in other major surgery.


Subject(s)
Colectomy/methods , Rectal Neoplasms/surgery , Rectum/surgery , Spinal Cord Injuries/complications , Aged , Aged, 80 and over , Humans , Middle Aged , Rectal Neoplasms/complications , Spinal Cord Injuries/diagnosis , Trauma Severity Indices , Treatment Outcome
13.
Anesth Analg ; 107(1): 325-32, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18635504

ABSTRACT

BACKGROUND: A previously published clinical trial of epidural-supplemented versus general anesthesia, Veterans Affairs Cooperative Study No. 345, showed no difference in 30-day mortality and morbidity rates between the two treatments. We hypothesized that long-term postoperative survival would be increased by epidural anesthesia/analgesia supplementation during colon cancer resection. METHODS: We studied long-term survival after resection of colon cancer in a trial of general anesthesia with and without epidural anesthesia and analgesia supplementation for resection of colon cancer in Veterans Affairs Cooperative Study No. 345. Cox and log-normal survival models were used to test the effects of pathological stage, type of anesthesia and other covariates on survival in 177 patients. RESULTS: The presence of distant metastases had the greatest effect on survival. Thus, analyses were performed separately for patients with and without metastases. For those without metastasis, the hazard ratio for the treatment effects changed at 1.46 years. Before 1.46 years, epidural supplementation was associated with improved survival (P = 0.012), while later, the type of anesthesia did not appear to affect survival (P = 0.27). Hypertension was associated with poorer survival (P = 0.029), as was alcoholism in patients who received epidural anesthesia (P = 0.014). Survival of patients with metastases was unaffected by type of anesthesia. There was a significant age by hypertension interaction (P = 0.002). Patients survived longer if they were hypertensive, but had reduced survival if they were older than 66 years and hypertensive. CONCLUSION: Epidural supplementation was associated with enhanced survival among patients without metastases before 1.46 years. Epidural anesthesia had no effect on survival of patients with metastases. Additional studies to confirm or refute these findings are warranted.


Subject(s)
Anesthesia, Epidural/methods , Colonic Neoplasms/mortality , Colonic Neoplasms/surgery , Age Factors , Aged , Alcoholism/complications , Colonic Neoplasms/pathology , Humans , Hypertension/complications , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Probability , Proportional Hazards Models , Randomized Controlled Trials as Topic
14.
J Cancer Educ ; 23(4): 248-52, 2008.
Article in English | MEDLINE | ID: mdl-19058075

ABSTRACT

BACKGROUND: Surveillance strategies for of rectal cancer patients after potentially curative treatment vary significantly. We investigated whether the age of the surgeon affects choice of surveillance strategy. METHODS: We developed vignettes depicting 4 generally healthy patients with rectal cancer of various stages who received various treatments. A questionnaire based on these vignettes was sent to the 1795 members of the American Society of Colon and Rectal Surgeons (ASCRS). RESULTS: There was no significant relationship between surgeon age and follow-up test-ordering schedules for any of the 4 vignettes. There was no significant relationship between surgeon age and 10 of the 11 possible motivating factors. CONCLUSIONS: Follow-up testing among ASCRS surgeons does not vary significantly among surgeons trained at various times. The motivation for follow-up testing is nearly uniform among age strata.


Subject(s)
Physicians/psychology , Postoperative Care/statistics & numerical data , Practice Patterns, Physicians'/trends , Rectal Neoplasms/diagnosis , Adult , Age Factors , Aged , Delivery of Health Care , Follow-Up Studies , Health Care Surveys , Humans , Middle Aged , Population Surveillance
15.
Int J Oncol ; 30(3): 735-42, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17273776

ABSTRACT

Most patients with rectal cancer are treated with curative-intent surgery; adjuvant chemotherapy and radiation are often used as well. A recent survey of members of the American Society of Colon and Rectal Surgeons (ASCRS) revealed considerable variation in surveillance intensity after primary treatment. We evaluated whether geographic factors may be responsible for the observed variation. Vignettes of hypothetical patients and a questionnaire based on the vignettes were mailed to the 1782 members of ASCRS. Repeated-measures analysis of variance was used to compare practice patterns, as revealed by the responses, according to US Census Regions and Divisions, Metropolitan Statistical Areas (MSA), and state-specific managed care organization (MCO) penetration rates. There was significant variation in surveillance intensity according to the US Census Region and Division in which the surgeon practiced. Non-US respondents employed CT of the abdomen and pelvis, chest radiography, and colonoscopy significantly more often than US respondents. MSA was not a significant source of variation. Surveillance patterns varied significantly by MCO penetration rate for office visits and CT of the abdomen and pelvis but not for other modalities. The US Census Region and Division in which the surgeon practices have a significant effect on surveillance intensity following completion of primary curative-intent therapy for rectal cancer patients. The MSA in which the surgeon practices does not affect surveillance intensity significantly and MCO penetration rate affects follow-up intensity minimally. All significant differences are clinically rather modest, however. These data should be useful in the design of controlled trials on this topic.


Subject(s)
Postoperative Care/methods , Rectal Neoplasms/epidemiology , Rectal Neoplasms/surgery , Delivery of Health Care , Follow-Up Studies , Geography , Humans , Medical Oncology/methods , Practice Patterns, Physicians' , Surveys and Questionnaires , Treatment Outcome , United States
16.
FEBS Lett ; 580(26): 6259-68, 2006 Nov 13.
Article in English | MEDLINE | ID: mdl-17070806

ABSTRACT

CRSBP-1, a membrane glycoprotein, can mediate cell-surface retention of secreted growth factors containing CRS motifs such as PDGF-BB. CRSBP-1 has recently been found to be identical to LYVE-1, a specific marker for lymphatic capillary endothelial cells. The in vivo role of CRSBP-1/LYVE-1 is unknown. CRSBP-1-null mice are overtly normal and fertile but exhibit identifiable morphological and functional alterations of lymphatic capillary vessels in certain tissues, marked by the constitutively increased interstitial-lymphatic flow and lack of typical irregularly-shaped lumens. The CRSBP-1 ligands PDGF-BB and HA enhance interstitial-lymphatic flow in wild-type mice but not in CRSBP-1-null animals.


Subject(s)
Glycoproteins/physiology , Lymphatic Vessels/pathology , Animals , Becaplermin , Glycoproteins/deficiency , Glycoproteins/genetics , Hyaluronic Acid/pharmacology , Ligands , Lymphatic System , Lymphatic Vessels/physiopathology , Membrane Transport Proteins , Mice , Mice, Knockout , Platelet-Derived Growth Factor/pharmacology , Proto-Oncogene Proteins c-sis
17.
Am J Surg ; 192(1): 100-8, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16769285

ABSTRACT

BACKGROUND: Colon cancer is relatively common; however, the results of treatment have marginally improved over the last half century. Though about 85% of patients have colorectal tumors resected with curative intent, a significant number of these patients will eventually die from cancer. As a result, many clinicians have advocated intensive follow-up in such patients as an attempt to increase survival. DATA SOURCES: A review of the literature focusing on studies that have specifically addressed postoperative surveillance programs in patients with colorectal cancer was conducted. Only studies with level A evidence were included. Further references were obtained through cross-referencing the bibliography cited in each work. CONCLUSION: One of the six prospective randomized studies demonstrated a statistically significant survival benefit. Undoubtedly, survival benefits can be shown with a well-designed evidence-based follow-up strategy. However, well-designed large prospective multi-institutional randomized studies are needed to establish a consensus for follow-up.


Subject(s)
Colonic Neoplasms/surgery , Population Surveillance , Postoperative Care/methods , Rectal Neoplasms/surgery , Colonic Neoplasms/diagnosis , Colonic Neoplasms/mortality , Follow-Up Studies , Humans , Rectal Neoplasms/diagnosis , Rectal Neoplasms/mortality , Survival Rate/trends
18.
Thorac Surg Clin ; 16(2): 125-31, v, 2006 May.
Article in English | MEDLINE | ID: mdl-16805201

ABSTRACT

The workup of patients suspected of having pulmonary metastases is complicated by the fact that a high percentage of pulmonary metastases are 6mm or less at presentation. Helical CT scans and high-resolution CT scans currently miss many of the lesions eventually detected at thoracotomy and many of the lesions detected are benign. The follow-up of patients after pulmonary metastasectomy is a controversial topic because of the lack of evidence-based practice guidelines. Though it is unlikely that current follow-up recommendations will ever be tested in randomized controlled trials, meta-analyses of existing retrospective data could improve the quality of the existing literature.


Subject(s)
Lung Neoplasms/diagnosis , Lung Neoplasms/surgery , Humans , Lung Neoplasms/secondary , Perioperative Care , Pneumonectomy , Practice Patterns, Physicians'
19.
J Spinal Cord Med ; 29(2): 133-7, 2006.
Article in English | MEDLINE | ID: mdl-16739556

ABSTRACT

BACKGROUND/OBJECTIVE: We sought to determine the clinical course of patients with spinal cord injury (SCI) who subsequently developed bronchogenic carcinoma and underwent pulmonary resection. METHODS: A nationwide retrospective study was conducted of all veterans at Department of Veterans Affairs Medical Centers for fiscal years 1993-2002 who were diagnosed with SCI, subsequently developed non-small cell lung cancer, and were surgically treated with curative intent. Inclusion criteria included American Spinal Injury Association type A injury (complete loss of neural function distal to the injury site) and traumatic etiology. Data were compiled from national Department of Veterans Affairs data sets and supplemented by operative reports, pathology reports, progress notes, and discharge summaries. RESULTS: Seven patients met the inclusion/exclusion criteria and were considered evaluable. Five (71%) had one or more comorbid conditions in addition to their SCIs. All 7 underwent pulmonary lobectomy. Postoperative complications occurred in 4 patients (57%). Two patients died postoperatively on days 29 and 499, yielding a 30-day mortality rate of 14% and an in-hospital mortality rate of 29%. CONCLUSIONS: This seems to be the only case study in the English language literature on this topic. Patients with SCI who had resectable lung cancer had a high incidence of comorbid conditions. Those who underwent curative-intent surgery had high morbidity and mortality rates. Available evidence suggests that SCI should be considered a risk factor for adverse outcomes in major surgery of all types, including operations for primary lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Pneumonectomy , Postoperative Complications/physiopathology , Spinal Cord Injuries/physiopathology , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Follow-Up Studies , Hospital Mortality , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Postoperative Complications/mortality , Retrospective Studies , Risk Factors , Spinal Cord Injuries/mortality , Survival Rate
20.
Am Surg ; 82(3): 278-80, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27099066

ABSTRACT

Barring unusual circumstances, sigmoid colostomy is the optimal technique for management of defecation in spinal cord injury (SCI) patients. We sought to provide evidence that a sigmoid colostomy is not difficult to perform in SCI patients and has better long-term results. The St. Louis Department of Veterans Affairs has a Commission on Accreditation of Rehabilitation Facilities (CARF)-approved SCI Unit. We reviewed the operative notes on all SCI patients who received a colostomy for fecal management by three ASCRS-certified colorectal surgeons at the St. Louis Department of Veterans Affairs from January 1, 2007 to November 26, 2012. There were 27 operations for which the recorded indication for surgery suggested that the primary disorder was SCI. Fourteen had traumatic SCI of the thoracic and/or lumbar spine and were evaluable. Of these 14 patients, 12 had laparoscopic sigmoid colostomy and two had open sigmoid colostomy. We encountered one evaluable patient with a remarkably large amount of retroperitoneal bony debris who successfully underwent laparoscopic sigmoid colostomy. In conclusion, sigmoid colostomy is the consensus optimal procedure for fecal management in SCI patients. Laparoscopic procedures are preferred. Care providers should specify sigmoid colostomy when contacting a surgeon.


Subject(s)
Colostomy/methods , Colostomy/standards , Defecation , Laparoscopy , Spinal Cord Injuries , Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Retrospective Studies , Spinal Cord Injuries/complications
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