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1.
In. Ministerio de Salud de Argentina-MSALARG y Desarrollo Social. Secretaria de Salud. Becas de investigación Ramón Carrillo - Arturo Oñativia: anuario 2015. Ciudad Autónoma de Buenos Aires, Ministerio de Salud y Desarrollo Social. Secretaria de Salud, Diciembre 2018. p.61-61.
Monography in Spanish | ARGMSAL, BINACIS | ID: biblio-997130

ABSTRACT

INTRODUCCIÓN La accesibilidad a los servicios públicos de salud representa un derecho. Desde las políticas públicas se debe garantizar su ejercicio. OBJETIVOS Conocer y analizar las opiniones, ideas y representaciones sociales que poseen los adultos mayores (AM) de dos zonas de la provincia de Salta en relación con la accesibilidad a los servicios de salud del sector público. MÉTODOS El estudio se enmarcó dentro de la metodología cualitativa. Se intentó construir un tipo de conocimiento que capte el punto de vista de quienes producen y viven la realidad social y cultural. Se recurrió al paradigma interpretativo, cuyo supuesto básico es la necesidad de comprender el sentido de la acción social en el contexto de vida y desde la perspectiva de los participantes. Resultados Los AM reconocen la atención de calidad como el principal factor que favorece su accesibilidad a los servicios públicos de salud. Se alude principalmente al aspecto vincular entre miembros del equipo de salud y usuarios, y también a la eficiencia y rapidez en la atención. Los AM consideran que las intervenciones comunitarias son otra de las formas en que los servicios públicos influyen en su estado de salud, y las sugieren como un modo de acompañar. DISCUSIÓN El envejecimiento poblacional es una materia pendiente en la agenda pública. Por ello, la relevancia de esta investigación radica en la posibilidad de profundizar el conocimiento en la temática desde una perspectiva que aborde la complejidad de la atención de esta población, recuperando la voz de la comunidad y enfatizando el derecho al acceso a la salud. Teniendo en cuenta las proyecciones estadísticas, es indispensable favorecer investigaciones que contribuían al diseño de políticas públicas con el objetivo de mejorar la calidad de atención y accesibilidad a los servicios.


Subject(s)
Humans , Social Behavior , Aged , Health Services Accessibility
2.
Cytometry B Clin Cytom ; 74(5): 319-29, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18431793

ABSTRACT

BACKGROUND: Flow cytometric analysis of human P2X(7) pore activity segregates variant from common P2RX7 genotypes and may serve as a biomarker for cancer, pain, inflammation, and immune responses to infection. Standardization is needed to accommodate variable sample age and instrumentation differences in a multicenter clinical trial. METHODS: CD14-PE-stained whole blood samples were treated with YO-PRO-1 combined with a P2X(7) agonist (BzATP) or control, followed by the addition of PI after closure of the P2X(7) pore. Recalled instrument settings from previous publications were used to adapt a standardized fluorescent particle-adjusted set-up method. Experiments were performed to compare the two methods while evaluating components of systematic variability and facilitating reliable processing of samples with varied ages. RESULTS: The median YO-PRO-1 fluorescence of BzATP-treated samples had less variability when collected by the bead-adjusted method and was less influenced by the compensation strategy used. The average day-to-day coefficient of variance for assessments of P2X(7) pore activity by this method was 0.11 +/- 0.04, and the exclusion of nonviable cells was found to accommodate samples aged up to 4 days after phlebotomy. The bead-adjusted set-up method produced measurements differing by only 2.0% +/- 1.5% on two analog cytometers, and within similar decades when comparing analog to digital instruments. CONCLUSIONS: These results provide a standardized method for quantitative flow cytometric analysis of P2X(7) receptor phenotypes in blood monocytes with minimal intralaboratory variation and potential for interlaboratory comparisons that can greatly facilitate multicenter functional genomic clinical studies.


Subject(s)
Clinical Trials as Topic , Flow Cytometry/methods , Multicenter Studies as Topic , Receptors, Purinergic P2/metabolism , Adenosine Triphosphate/analogs & derivatives , Aging/drug effects , Asthma/diagnosis , Benzoxazoles , Cell Survival/drug effects , Flow Cytometry/instrumentation , Fluorescence , Humans , Lipopolysaccharide Receptors/metabolism , Monocytes/cytology , Monocytes/drug effects , Phlebotomy , Quinolinium Compounds , Receptors, Purinergic P2X7
3.
Urologe A ; 44(11): 1324-31, 2005 Nov.
Article in German | MEDLINE | ID: mdl-16133227

ABSTRACT

Therapeutic success and prognosis in RRP is determined by negative surgical margins. In order to minimize the proportion of positive surgical margins in the final histological evaluation, valid intraoperative control by means of frozen margin analysis is indispensable. We have developed and evaluated a new frozen margin procedure based on the Stanford method with transverse and sagittal cut directions. This technique facilitates comprehensive intraoperative evaluation of curved margin areas for the first time. Retrospective analysis of the results of the new frozen section technique revealed positive surgical margins in 2.7% of patients. The results obtained with this new technique were significantly superior to those obtained with two established techniques (10.3%, P < or =0.001; 17.2%, P < or =0.001). Our results demonstrate that the new frozen margin technique is clearly more sensitive for intraoperative detection of positive margins and thus leads to substantially higher rates of negative surgical margins.


Subject(s)
Cryoultramicrotomy/methods , Neoplasm Recurrence, Local/prevention & control , Prostatectomy/methods , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Cryoultramicrotomy/statistics & numerical data , Germany/epidemiology , Humans , Intraoperative Care/methods , Intraoperative Care/statistics & numerical data , Male , Neoplasm Recurrence, Local/epidemiology , Prostatectomy/statistics & numerical data , Prostatic Neoplasms/epidemiology , Reoperation , Retrospective Studies , Treatment Outcome
4.
J Appl Physiol (1985) ; 95(3): 969-76, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12730143

ABSTRACT

The purpose of this study was to determine the role of the CD11b-dependent respiratory burst in neutrophil oxidant generation and activation, interleukin-8 (IL-8) production, and myofiber damage after muscle stretch injury by using the monoclonal antibody M1/70 to block this pathway. Twelve male New Zealand White rabbits were randomly assigned to a treatment group: M1/70 (n = 6), IgG isotype control (n = 3), or saline control (n = 3). After intravenous injection of the assigned agent under gas anesthesia, a standardized single-stretch injury was created in the right tibialis anterior, whereas the left tibialis anterior underwent a sham surgery. Blood-borne neutrophil oxidant generation and CD11b receptor density and plasma IL-8 levels were measured pre- and 24 h postinjury. Damage was assessed histologically at the hematoma site by counting torn myofibers. M1/70 group demonstrated decreased blood-borne neutrophil oxidant generation (P < 0.05) and CD11b receptor density (P < 0.05), an increase in plasma IL-8 concentration (P < 0.01), and less torn myofibers (P < 0.01) compared with IgG isotype or saline control groups. These data indicate that 1). CD11b-dependent respiratory burst is a major source of oxidants produced by the neutrophil, and that treatment with M1/70 2). attenuates neutrophil activation status, 3). increases plasma IL-8 concentration, and 4). minimizes myofiber damage 24 h postmuscle stretch injury.


Subject(s)
Antibodies, Monoclonal/pharmacology , Muscle Fibers, Skeletal/pathology , Muscle, Skeletal/injuries , Muscle, Skeletal/pathology , Neutrophil Activation/drug effects , Neutrophils/metabolism , Oxidants/metabolism , Animals , CD11b Antigen/metabolism , CD11b Antigen/physiology , Cell Count , Cell Survival , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Immunohistochemistry , Interleukin-8/blood , Leukocyte Count , Male , Neutrophils/drug effects , Rabbits , Respiratory Burst/drug effects , Tendon Injuries/pathology
6.
Percept Mot Skills ; 92(1): 53-71, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11322606

ABSTRACT

Participants filled 42 orders on a task designed to simulate components of filling prescriptions. Task factors included objective workload of 70- versus 80-min. to complete the task and perceptions of workload dimensions using the NASA Task Load Index. The proportion and pattern of data-entry, counting, and product-selection errors were compatible with those found in pharmacy field-sites. Significant other relationship stress, field-dependence, and an 80-min. workpace predicted data-entry errors. Mistakes in product selection were associated with low GPA, high social stress, the NASA Task Load Index dimension of less concern with performing well, and a 70-min. workpace. Relationship of data to corresponding information in the pharmacy literature and to assumptions of a cognitive-systems performance model was discussed.


Subject(s)
Drug Prescriptions , Fatigue/psychology , Pharmaceutical Services/standards , Workload , Adult , Female , Humans , Male , Middle Aged , Random Allocation , Visual Perception/physiology
7.
Pediatr Nurs ; 27(2): 141-6, 2001.
Article in English | MEDLINE | ID: mdl-12962250

ABSTRACT

Unintentional injury remains the leading cause of death in U.S. children. This article provides a case evaluation of a school based youth safety education program based on the Think First National Injury Prevention Program curriculum. Partners for the program included an urban elementary school, a school of nursing, a Safe Kids Coalition, a regional trauma center, and pediatric, community, and critical care nurses. A convenience sample of 140 second grade children in a mid-Atlantic elementary school participated in a 1 hour-a-week injury prevention class over the course of 6 weeks. The Think First National Injury Prevention Program served as the core curriculum and evaluation framework. At the end of the program, knowledge test scores increased an average of 35% over pre-test measures. Ninety-eight percent of the faculty, staff nurses, student nurses, children, and parents indicated a positive overall value of the program and the need for it to continue on an ongoing basis. Safety resources are provided for pediatric nurses to use in their diverse practice settings.


Subject(s)
Public Health , Safety Management , Wounds and Injuries/prevention & control , Child , Child Behavior , Health Behavior , Humans
8.
Percept Mot Skills ; 93(3): 879-98, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11806614

ABSTRACT

This study was designed to assess the effect of participants' sex and two performance-enhancing interventions on performance in a laboratory-based product-assembly task. The task environment simulated dispensing medications as in a pharmacy. 33 men and 39 women worked in the simulation, completing four sets of orders totaling 114 products. Participants either worked with no interventions, with a copy strip to aid in data entry, or with both the copy strip and bottle sleeves to aid in stimulus selection during assembly. Analysis indicated that accuracy and pacing improved during the task as a function of the number of interventions available. Also, these improvements were not subject to effects of sex. It was concluded that the interventions tested in this study to aid in performance during product-assembly tasks like filling prescriptions are equally beneficial to both men and women. Ideas for research are discussed.


Subject(s)
Attention , Gender Identity , Psychomotor Performance , Stereotyped Behavior , Task Performance and Analysis , Adolescent , Adult , Cues , Female , Humans , Male , Middle Aged , Pharmaceutical Services , Stress, Psychological/complications , Type A Personality
9.
Cytometry ; 41(2): 89-95, 2000 Oct 01.
Article in English | MEDLINE | ID: mdl-11002263

ABSTRACT

BACKGROUND: 5-Bromo-2'-deoxyuridine (BrdU) is a powerful compound to study the mitotic activity of a cell. Most techniques that identify BrdU-labeled cells require conditions that kill the cells. However, the fluorescence intensity of the membrane-permeable Hoechst dyes is reduced by the incorporation of BrdU into DNA, allowing the separation of viable BrdU positive (BrdU+) cells from viable BrdU negative (BrdU-) cells. METHODS: Cultures of proliferating cells were supplemented with BrdU for 48 h and other cultures of proliferating cells were maintained without BrdU. Mixtures of viable BrdU+ and viable BrdU- cells from the two proliferating cultures were stained with Hoechst 33342. The viable BrdU+ and BrdU- cells were sorted into different fractions from a mixture of BrdU+ and BrdU- cells based on Hoechst fluorescence intensity and the ability to exclude the vital dye, propidium iodide. Subsequently, samples from the original mixture, the sorted BrdU+ cell population, and the sorted BrdU- cell population were immunostained using an anti-BrdU monoclonal antibody and evaluated using flow cytometry. RESULTS: Two mixtures consisting of approximately 55% and 69% BrdU+ cells were sorted into fractions consisting of greater than 93% BrdU+ cells and 92% BrdU- cells. The separated cell populations were maintained in vitro after sorting to demonstrate their viability. CONCLUSIONS: Hoechst fluorescence intensity in combination with cell sorting is an effective tool to separate viable BrdU+ from viable BrdU- cells for further study. The separated cell populations were maintained in vitro after sorting to demonstrate their viability.


Subject(s)
Benzimidazoles/pharmacology , Bromodeoxyuridine/pharmacology , Cell Survival , Flow Cytometry , 3T3 Cells , Animals , Antibodies, Monoclonal/immunology , Antimetabolites/pharmacology , Bromodeoxyuridine/immunology , Cell Separation , Cells, Cultured , DNA/analysis , Fluorescent Dyes/pharmacology , Indicators and Reagents/pharmacology , Intercalating Agents/pharmacology , Male , Mice , Mitosis , Muscle, Skeletal/cytology , Propidium/pharmacology , Rats
10.
Percept Mot Skills ; 90(2): 547-61, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10833753

ABSTRACT

This study examined the effects of scores on state anxiety on overall accuracy of performance and speed of working in a simulated pharmacy dispensing task. 75 undergraduates worked in a simulated pharmacy environment, designed by Schell and Grasha in 1998, to fill 42 mock orders for simulated pharmacy items. Participants' accuracy and work pace in the simulation, presimulation stress, and postsimulation perceived workload and state anxiety were measured. Analysis indicated that state anxiety and overall accuracy were strongly related. State anxiety appears to be one of the best predictors of errors in the simulated pharmacy dispensing task found so far, while the lack of relationship between work pace and accuracy was confirmed. Work pace predicted accuracy, indirectly, but only after statistically removing the effects of anxiety, task frustration, significant-other stress, and grade point average.


Subject(s)
Anxiety/psychology , Personality Inventory/statistics & numerical data , Pharmaceutical Services/standards , Task Performance and Analysis , Workload/psychology , Humans , Stress, Psychological/psychology , Time and Motion Studies
11.
Cancer Immunol Immunother ; 49(2): 85-93, 2000 May.
Article in English | MEDLINE | ID: mdl-10823418

ABSTRACT

The aim of this study was to compare the antigenicity of human melanoma cells molecularly modified by particle-mediated gene transfer to have transient or stable expression of the B7-1 co-stimulatory molecule (CD80). The unmodified melanoma cells (mel5, m21) had no constitutive expression of B7-1, but 22%-28% of cells had transient B7-1 expression 24 h following transfection with cDNA for B7-1 (mel5-B7, m21-B7). In addition, 85%-90% of cells had stable B7-1 expression following transfection with cDNA for B7-1 and in vitro culture under selection conditions (mel5-B7neo, m21-B7neo). Allogeneic HLA-unmatched normal donor peripheral blood mononuclear cells (PBMC) secreted greater amounts of granulocyte/macrophage-colony-stimulating factor (GM-CSF) when incubated for 3 days with m21-B7neo than did PBMC incubated with m21-B7, which, in turn, secreted greater amount of GM-CSF than PBMC incubated with m21. Similarly, cell-mediated cytotoxicity against unmodified melanoma cells by PBMC co-cultured for 5 days with the modified or unmodified melanoma cells was proportional to the level of B7-1 expression on the stimulating cells. This cytolytic activity had both an HLA-class-I-restricted and an HLA-class-I-unrestricted component. Following 5 days of co-culture, PBMC expression of CD28, the ligand for B7-1, was down-regulated in proportion to the level of B7-1 expression on the stimulating melanoma cells. Thus, particle-mediated gene delivery of cDNA for B7-1 into human melanoma cells increased expression of functional B7-1 and enhanced the antigenicity of the gene-modified cells in proportion to their level of B7-1 expression.


Subject(s)
B7-1 Antigen/physiology , Melanoma/immunology , B7-1 Antigen/genetics , Cytokines/biosynthesis , Cytotoxicity, Immunologic , HLA-A Antigens/genetics , Humans , Immunophenotyping , Lymphocyte Activation , Transfection , Tumor Cells, Cultured
12.
Circulation ; 101(12): 1423-9, 2000 Mar 28.
Article in English | MEDLINE | ID: mdl-10736287

ABSTRACT

BACKGROUND: Triiodothyronine (T(3)) supplementation may be a useful adjunct in the management of patients after cardiopulmonary bypass. Limited data are available regarding the use and pharmacokinetics of T(3) in children. The present study was performed to evaluate T(3) pharmacokinetics in a cohort of children undergoing the modified Fontan procedure. METHODS AND RESULTS: A total of 28 patients were enrolled in this randomized, prospective study. The patients were divided into 4 groups: 1 group received a placebo and 3 groups received intravenous T(3) at dosages of 0.4, 0.6, and 0.8 microg/kg, respectively. All 28 patients survived their operative procedures. Two patients developed low cardiac output, and 3 patients had pleural effusions. The median length of hospital stay was 7 days. The mean free T(3) level was 316+/-67 pg/dL after then administration of a placebo. Patients who received T(3) had mean peak free T(3) levels of 972+/-88, 1351+/-299, and 1869+/-281 pg/dL for the dosages of 0.4, 0.6, and 0.8 microg/kg, respectively. The calculated half-life of T(3) was 7 hours. CONCLUSIONS: The half-life of intravenous T(3) in children is approximately one-third of that reported for adults. These results provide a framework for studying the efficacy of T(3) supplementation in children undergoing open-heart surgery.


Subject(s)
Fontan Procedure , Triiodothyronine/pharmacokinetics , Cardiac Output , Child, Preschool , Half-Life , Heart Defects, Congenital/surgery , Humans , Injections, Intravenous , Length of Stay , Pleural Effusion/etiology , Postoperative Complications , Prospective Studies , Thyroglobulin/blood , Thyrotropin/blood , Triiodothyronine/administration & dosage
13.
Mol Pharmacol ; 56(3): 515-25, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10462539

ABSTRACT

Okadaic acid (OA), a toxin from the black sponge Halicondria okadai, is a specific inhibitor of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A). OA is a tumor promoter but also induces apoptosis in some tumor cell lines. In this study, we determined whether ras mutation and/or p53 status are characteristics associated with the cell's sensitivity to the induction of apoptosis by OA. Several cell lines that differed in ras and p53 mutations were treated with OA (10-100 nM). At 24 to 48 h after treatment, the percentage of cells undergoing apoptosis was quantitated. The cell lines with mutations in either H-ras (human bladder carcinoma cell line T24 and mouse keratinocyte cell line 308), or K-ras (human colon carcinoma cell lines DLD-1 and HCT116; human prostate cancer cell lines LNCaP and PC-3; human lung cancer cell lines Calu-6 and SKLU-1; and human pancreatic cancer cell line MIAPaCa2) were more sensitive to OA-induced apoptosis (3- to 10-fold) than the cell lines that lacked the ras mutation (mouse epidermal cell lines C50 and JB6; murine fibroblast cell line NIH3T3; human colon cancer cell line HT29; human kidney epithelial cell line Hs715.K; and human pancreatic cancer cell line Bx-PC3). Similarly, using isogenic cell lines we found that overexpression of mutated H-ras in NIH3T3 and in SV40 immortalized human uroepithelial cells (SVHUC) enhanced their sensitivity to undergo apoptosis in response to OA treatment. The T24, DLD-1, SKLU-1, Calu-6, and MIAPaCa2 cell lines express mutated p53. The SVHUC as well as their ras-transfected counterparts have inactive p53 due to complex formation between large "T" antigen and p53. Taken together, these results imply that OA-induced apoptosis may involve a p53-independent pathway. The transfectants (NIH3T3-ras and SVHUC-ras), which express mutated H-ras, have up-regulated PP2A activity. OA treatment inhibited in vivo the levels of PP1 and PP2A activity, and induced apoptosis in SVHUC-ras and other cell lines. We conclude that OA-induced cell death pathway in ras-activated cell lines may involve a cross talk between PP1 and PP2A and ras signaling pathways. In light of the present results, the current theory that OA promotes mouse skin tumor formation by selective expansion of initiated cells that harbor ras mutations needs reevaluation.


Subject(s)
Apoptosis , Okadaic Acid/pharmacology , Phosphoprotein Phosphatases/metabolism , Tumor Suppressor Protein p53/physiology , ras Proteins/genetics , 3T3 Cells , Animals , Apoptosis/genetics , Apoptosis/physiology , Cell Cycle/drug effects , Enzyme Inhibitors/pharmacology , Genes, ras/physiology , Humans , Mice , Mutation , Phosphoprotein Phosphatases/antagonists & inhibitors , Protein Phosphatase 1 , Tumor Cells, Cultured , Up-Regulation , ras Proteins/physiology
14.
Nurse Educ ; 23(5): 8-12, 1998.
Article in English | MEDLINE | ID: mdl-9866554

ABSTRACT

Although critical thinking is an essential student skill, strategies that promote critical thinking are not always employed in nursing education. Fostering student questioning is one strategy that can be integrated in both the classroom and clinical setting. Some research results indicate that student questioning improves problem solving. However, students told to seek answers must first learn to ask questions. Students can be taught and encouraged to question through a variety of methods the author discusses in this article.


Subject(s)
Students, Nursing/psychology , Teaching/methods , Thinking , Faculty, Nursing , Humans
15.
Psychol Rep ; 83(2): 443-52, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9819919

ABSTRACT

Predictions based on cognitive balance and mood induction theories were used to investigate how participants reacted to positive or negative feedback on a Q-sorting task. Positive and negative feedback was presented by giving some participants positive and negative adjectives with which to describe themselves, while giving a third group of participants neutral adjectives. The effect of the feedback was assessed by correlating self-descriptions with reference to their current self, how they remembered being in the past, and how they wanted to be in the future. These correlations were then compared across groups. The mean correlations between the current self-description and other self-descriptions were significantly lower for the positive and negative groups than they were for the control group. These findings appear to support the concept of cognitive balance and also indicate a possible chronological basis for balancing self-descriptions across a life span.


Subject(s)
Affect , Internal-External Control , Q-Sort , Self Concept , Adolescent , Adult , Feedback , Female , Humans , Male , Middle Aged
16.
Crit Care Med ; 26(10): 1744-8, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9781734

ABSTRACT

OBJECTIVES: To determine the clinical effects of intravenous terbutaline at >0.4 microg/kg/min in children with status asthmaticus; to describe the clinical findings associated with such therapy, including creatinine phosphokinase-myocardial band isoenzyme (CPK-MB) concentrations, electrocardiographic alterations, and decreased diastolic blood pressure (DBP) with terbutaline usage; and to assess the requirement for epinephrine to counteract the decrease in diastolic blood pressure. DESIGN: A retrospective review of children admitted with status asthmaticus who failed emergency room therapy and required intravenous terbutaline. SETTING: San Diego Children's Hospital Pediatric Intensive Care Unit. PATIENTS: Eighteen children with status asthmaticus, based on clinical and laboratory criteria, between September 1994 and July 1996. INTERVENTIONS: Epinephrine was added for below-normal decreases in diastolic blood pressure. MEASUREMENTS AND MAIN RESULTS: Continuous monitoring for arrhythmias, ST-segment changes, and DBP values during variations in the dose of intravenous terbutaline, with or without epinephrine. CPK-MB concentrations were determined in 15 of 18 patients. CONCLUSIONS: Intravenous terbutaline was well tolerated in asthmatic children for < or =305 continuous hours and at varying doses up to a maximum of 10 microg/kg/min. There was no relationship between the magnitude of CPK-MB concentrations and the terbutaline or epinephrine doses used. Arrhythmias were rare and not related to either terbutaline or epinephrine doses. However, ST-segment depression did occur in two patients requiring high-dose epinephrine. Terbutaline significantly lowered DBP when used between 0.4 and 1.0 microg/kg/min, which required epinephrine to be initiated. Epinephrine was not required at terbutaline doses of >2 microg/kg/min. There was no mortality.


Subject(s)
Bronchodilator Agents/therapeutic use , Status Asthmaticus/drug therapy , Terbutaline/therapeutic use , Adolescent , Arrhythmias, Cardiac/chemically induced , Blood Pressure/drug effects , Child , Child, Preschool , Creatine Kinase/blood , Drug Monitoring , Drug Therapy, Combination , Electrocardiography , Epinephrine/therapeutic use , Female , Humans , Infusions, Intravenous/methods , Isoenzymes , Male , Retrospective Studies , Status Asthmaticus/metabolism , Status Asthmaticus/physiopathology , Time Factors
17.
Cancer Lett ; 111(1-2): 111-5, 1997 Jan 01.
Article in English | MEDLINE | ID: mdl-9022135

ABSTRACT

It has been proposed that immunoregulatory cytokines play a role in the onset and development of cancer cachexia, although evidence supporting this theory remains inconclusive. In the present study, SCID mice were implanted with one of two tumor cell lines known to induce weight loss in rats. Growth of the Morris 7777 hepatoma was associated with weight loss as well as increased levels of tumor necrosis factor and interleukins 1 and 6 in spleen cells of tumor-bearing mice. Growth of the MCA sarcoma did not induce weight loss, nor did it increase cytokine expression in spleen cells of tumor-bearing mice. We conclude that increased cytokine expression is associated with weight loss in tumor-bearing SCID mice, and immune activation for cytokine expression does not require the presence of T or B cells.


Subject(s)
Interleukin-1/metabolism , Interleukin-6/metabolism , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms, Experimental/physiopathology , Neoplasm Proteins/metabolism , Sarcoma, Experimental/metabolism , Sarcoma, Experimental/physiopathology , Tumor Necrosis Factor-alpha/metabolism , Weight Loss/physiology , Animals , Liver Neoplasms, Experimental/pathology , Male , Mice , Mice, SCID , Rats , Rats, Inbred BUF , Sarcoma, Experimental/pathology , Species Specificity
18.
J Immunother Emphasis Tumor Immunol ; 19(4): 278-95, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8877722

ABSTRACT

The induction of human antimouse antibodies (HAMA) and human anti-idiotypic (anti-Id) responses in cancer patients receiving therapeutic monoclonal antibody (mAb) may limit the effectiveness of the administered mAb. This report evaluates the influence of systemic interleukin-2 (IL-2) on the anti-Id response to anti-disialoganglioside (anti-GD2) antibody given as treatment for patients with melanoma. Twenty-eight patients with melanoma received combined immunotherapy with anti-GD2 antibody and IL-2 at 1.5 x 10(6) U/m2/day given 4 days/week. The anti-GD2 antibody [murine 14.G2a mAb; dose levels of 2-5 mg/m2/day (4 patients); or human-mouse chimeric 14.18 (ch14.18) antibody; dose levels of 2-10 mg/m2/day (24 patients)] was scheduled to be given for 5 days either before, during, or after initial systemic IL-2 treatment. All four patients who received murine 14.G2a developed HAMA anti-isotype antibodies (660-1,000 ng/ml) as well as measurable anti-Id antibodies. All three patients who received initial treatment with ch14.18 alone developed a strong anti-Id antibody response after IL-2 was started 1 week later. The serum level of anti-Id antibody decreased during subsequent ch14.18 infusions, suggesting that the anti-Id antibody may be binding the administered ch14.18. In contrast, measurable anti-Id antibody was detected in only 3 of 14 patients who received IL-2 before, during, and after initial ch14.18 administration. Two of four patients receiving systemic IL-2 before and during initial ch14.18 infusions, and two of three patients receiving systemic IL-2 concurrent with initial ch14.18 infusions developed anti-Id antibodies. These data suggest that the anti-Id response to chimeric anti-GD2 antibody is influenced by the timing of systemic IL-2 in relation to antibody administration and can be suppressed by systemic treatment with IL-2 given before, during, and after the antibody administration.


Subject(s)
Adjuvants, Immunologic/pharmacology , Antibodies, Anti-Idiotypic/biosynthesis , Antibodies, Monoclonal/therapeutic use , Gangliosides/immunology , Immunoglobulin Idiotypes/immunology , Interleukin-2/pharmacology , Melanoma/immunology , Antibodies, Anti-Idiotypic/drug effects , Antibodies, Monoclonal/immunology , Antibody-Dependent Cell Cytotoxicity , Drug Synergism , Humans , Infusions, Intravenous , Interleukin-2/administration & dosage , Interleukin-2/therapeutic use , Melanoma/therapy , Recombinant Proteins/administration & dosage , Recombinant Proteins/immunology , Recombinant Proteins/therapeutic use , Skin Neoplasms/immunology , Skin Neoplasms/therapy
19.
Cancer Gene Ther ; 3(3): 192-201, 1996.
Article in English | MEDLINE | ID: mdl-8725884

ABSTRACT

The aim of this study was to determine if human melanoma cells could be molecularly modified by particle-mediated gene transfer with a "gene gun", using genes for interferon-gamma (IFN-gamma), the B7-1 costimulatory molecule (CD80), and human leukocyte antigen (HLA)-A2, to augment expression of both HLA molecules and B7-1. Established and early passage melanoma cells transfected with human IFN-gamma complementary DNA (cDNA) produced IFN-gamma (50-5,000 pg/mL). The biological effect of this IFN-gamma transgene included an upregulation, or de novo appearance, of HLA expression. These melanoma cells had no detectable baseline surface expression of the B7-1 costimulatory molecule, but 8% to 31% of these cells became B7-1 positive with no selection procedure after gene transfer with human B7-1 cDNA. After combination gene transfer with cDNAs for both IFN-gamma and B7-1, 9% to 33% of these cells expressed both HLA-DR and B7-1. In combination gene transfer experiments with cDNAs for both HLA-A2 and B7-1, dual expression of HLA-A2 and B7-1 was achieved in 10% to 17% of the melanoma cells. Thus, the molecular modification of human melanoma cells to increase expression of both HLA and B7-1 can be achieved by particle-mediated gene delivery and presents a promising strategy to stimulate antimelanoma T-cell immunity. Key words: Melanoma; T cells; B7-1 costimulatory molecule (CD80); major histocompatibility complex.


Subject(s)
B7-1 Antigen/biosynthesis , HLA Antigens/biosynthesis , Interferon-gamma/biosynthesis , Melanoma , Transfection/methods , B7-1 Antigen/genetics , Biolistics , Cell Line , DNA, Complementary , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Gene Expression , Genes, Reporter , Genetic Therapy/methods , HLA-A2 Antigen/biosynthesis , HLA-DR Antigens/biosynthesis , Humans , Interferon-gamma/genetics , Major Histocompatibility Complex , Melanoma/therapy , Plasmids , Recombinant Proteins/biosynthesis , Tumor Cells, Cultured , beta-Galactosidase/biosynthesis
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