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Biomedical subjects

J M Daly

Publications and source records attributed to J M Daly.

At least 73 records · Page 4Linked to original sources

National Cancer Data Base report on esophageal carcinoma.

BACKGROUND: The prognosis for patients with esophageal carcinoma is poor, with less than fifty percent surviving 1 year after diagnosis. Although diagnostic and staging methods have improved, a large proportion of patients present with advanced disease. Research is being conducted to determine what multimodality treatment regimens provide the best local control and survival. METHODS: Using the National Cancer Data Base's most current accrual of oncologic data for cases diagnosed in 1988 and 1993, patterns of care and outcome were analyzed for esophageal carcinoma. RESULTS: A substantial increase was demonstrated between 1988 and 1993 in the proportion of esophageal adenocarcinomas and patients presenting with Stage IV disease. The therapeutic regimen most frequently employed in 1993 was combined radiation therapy and chemotherapy, which rose 8.2% from 2.2% in 1988. CONCLUSIONS: The dramatic rise across the years of this study in the occurrence of esophageal adenocarcinomas indicates a need for developing strategies to evaluate Barrett's preneoplastic mucosal changes more precisely. The increasing use of combined chemotherapy and radiation therapy reflects the results of randomized trials that have demonstrated improved response and outcome for this combined regimen compared with radiation therapy alone. There was no substantial increase in the use of surgical resection with chemotherapy and radiation therapy throughout these years.

Adenocarcinoma↗

Dominance of T-helper 2-type cytokines after severe injury.

OBJECTIVE: To determine whether severe injury leads to a dominance of splenocyte-produced T-helper (Th) 2-type cytokines, partly explaining the observed defects in cellular immune responses in the posttraumatic state. DESIGN: Female BALB/c mice (n = 6 per group) were randomized to receive anesthesia alone (control) or a combined femur fracture and a hemorrhage of 40% of total blood volume (trauma). On days 1 and 7 after injury, mice were killed and spleens were harvested. Splenocytes were stimulated in vitro with 2.5 micrograms of concanavalin A per milliliter. After 72 hours of incubation, splenocyte proliferation was determined by means of tritiated thymidine uptake. Production of interferon-gamma and interleukins (IL) -2, -4, -5, -6, and -10 from supernatants harvested after 24 or 72 hours of incubation was quantified by enzyme-linked immunosorbent assay. SETTING: Surgical immunology research laboratory of a medical college. MAIN OUTCOME MEASURES: Mouse spleen weight, splenocyte number, and proliferation in addition to cytokine production (interferon-gamma, IL-2, IL-4, IL-5, IL-6, and IL-10). RESULTS: Splenocyte proliferative capacity was unaffected at day 1 after injury but was significantly suppressed (P < .05) by day 7 after injury. Similarly, there were no changes in splenocyte cytokine production in a comparison of control and injured mice at day 1. At day 7, however, there was nearly a 90% decrease in the Th1-type cytokines (interferon-gamma and IL-2; P < or = .002) and at least a 30% increase in the Th2-type cytokines IL-4, IL-5, IL-6, and IL-10 (P = .06 for IL-6 and P < or = .03 for IL-4, IL-5, and IL-10). CONCLUSIONS: These data indicate that a shift to a Th2-type splenocyte cytokine response occurs late, at 7 days after injury. Modulation of Th cell cytokine responses may partially explain defects observed in cellular immune responses in postinjury states. Therapies that augment Th1-type cytokine production and/or neutralize Th2-type cytokines may prove beneficial.

Animals↗

Diarrhea and Clostridium difficile-associated diarrhea on a surgical service.

OBJECTIVE: To identify the incidence, risk factors, and treatment of diarrhea and Clostridium difficile-associated diarrhea (CDAD) in surgery patients. DESIGN: Prospective and historical retrospective analysis. SETTING: Major urban tertiary care referral hospital. PATIENTS: Consecutive patients (N = 475) admitted to the vascular, trauma, and general surgical surgery services, prospectively evaluated during a 10-week period. A retrospective historical control of the same surgical services was used for comparison. INTERVENTION: None. MAIN OUTCOME MEASURES: Incidence of diarrhea and CDAD, use of bowel preparations, surgical procedure, use of C difficile toxin assay, white blood cell count, symptoms, treatment, and delay in hospital discharge. RESULTS: The incidence of diarrhea in surgery patients analyzed prospectively was 6.1%; the incidence of CDAD during the prospective and retrospective periods was 2%. Preoperative bowel preparations were associated with an increased risk of diarrhea (relative risk, 4.2; 95% confidence interval, 2.6-6.8; P < .001) and CDAD (relative risk, 3.2; 95% confidence interval, 1.5-7.2; P < .03). Leukocytosis (white blood cell count > 11 x 10(9)/L) was significantly higher in the CDAD group compared with the diarrhea group only on the day of diagnosis (P < .05). By subjective analysis, diarrhea was directly responsible for a delay in discharge in 7 of 29 patients for a mean (+/-SEM) of 4.0 +/- 1.0 days. CONCLUSIONS: Patients undergoing preoperative bowel preparations are at increased risk of experiencing diarrhea and CDAD. Among patients with diarrhea, an elevated white blood cell count may help identify those with C difficile. Early treatment of diarrhea with oral metronidazole while awaiting the results of the stool toxin assay is recommended for treating diarrhea in surgery patients. Prophylactic treatment of surgery patients undergoing bowel preparations should be considered.

Aged↗

Elevation of intracellular cyclic adenosine monophosphate inhibits the epidermal growth factor signal transduction pathway and cellular growth in pancreatic adenocarcinoma cell lines.

BACKGROUND: The epidermal growth factor (EGF) signal transduction pathway, frequently activated in pancreatic cancer, is an important regulator of cellular growth and transformation. This study examined whether activation of the cyclic adenosine monophosphate protein kinase A pathway may inhibit the EGF signal transduction pathway in pancreatic cancer cell lines. METHODS: Human pancreatic cancer lines BxPC-3 and AsPC-1 were stimulated with EGF, forskolin, or both. Forskolin is a compound that increases cyclic adenosine monophosphate levels. Assays of cell lines were then obtained for cellular growth (MTT assay), anchorage-independent growth (soft agar), and EGF-induced mitogen-activated protein kinase activation as measured by an in-gel kinase assay. RESULTS: Treatment with forskolin resulted in inhibition of EGF-induced activation of mitogen-activated protein kinase activity (BxPC-3 78% inhibition and AsPC-1 70% inhibition, p < 0.005), diminished cellular proliferation (BxPC-3 92% inhibition and AsPC-1 86% inhibition, p < 0.001), and formation of colonies in soft agar (BxPC-3 98% inhibition and AsPC-1 76% inhibition, p < 0.001). Forskolin did not inhibit EGF receptor autophosphorylation or tyrosine kinase signaling in response to EGF. CONCLUSIONS: Forskolin-induced inhibition of mitogen-activated protein kinase is associated with diminished pancreatic cancer cell proliferation in vitro. Use of strategies to increase cyclic adenosine monophosphate levels may have therapeutic application in pancreatic cancer.

Adenocarcinoma↗

Antigenic and genetic evolution of equine H3N8 influenza A viruses.

Evolution of equine influenza a H3N8 viruses was examined by antigenic and genetic analysis of a collection isolates from around the world. It was noted that antigenic and genetic variants of equine H3N8 viruses cocirculate, and in particular that variants currently circulating in Europe and the USA are distinguishable from one another both in terms of antigenic reactivity and genetic structure of the HA1 portion of the haemagglutinin (HA) molecule. Whilst the divergent evolution of American and European isolates may be due to geographical isolation of the two gene pools, some mixing is believed to occur as 'American-like' viruses have been isolated during outbreaks of equine influenza in the UK. The cocirculation of two antigenically and genetically distinct lineages of equine influenza H3N8 viruses has serious implications for vaccine strain selection.

Amino Acid Sequence↗

Newborn readmissions.

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Continuity of Patient Care↗

Antimicrobial effects of granulocyte-macrophage colony-stimulating factor in protein-energy malnutrition.

OBJECTIVES: To evaluate, in a murine model of protein-energy malnutrition, whether granulocyte-macrophage colony-stimulating factor (GM-CSF) improves the host response to a septic challenge and to determine the potential mechanisms involved. DESIGN: Nonblinded study of GM-CSF in mice with protein-energy malnutrition. SETTING: A university-based surgical laboratory and animal facility. INTERVENTION: In study 1, malnourished mice were randomized to receive either GM-CSF (120 micrograms/kg subcutaneously to receive either GM-CSF (120 micrograms/kg subcutaneously from day 4 to 7 of the protein-free diet) or saline vehicle as a control. On day 7, all mice were given Candida albicans (5 x 10(5) organisms intravenously). In study 2, malnourished mice received the same dose of GM-CSF or saline vehicle for 7 days of the protein-free diet. MAIN OUTCOME MEASURES: In study 1 mice were followed up for survival. In study 2, after 7 days of diets, splenic macrophages were harvested and were assayed for interleukin-6, superoxide anion, and nitric oxide production. Splenocytes were stimulated with concanavalin A (5 micrograms/mL) for interleukin-4, interleukin-10, and interferon-gamma production. RESULTS: Treatment with GM-CSF significantly enhanced survival in malnourished mice infected with C albicans. Treatment with GM-CSF was associated with increased production from splenic macrophages of interleukin-6, superoxide anion, and nitric oxide as well as decreased interleukin-4 production from splenocytes. CONCLUSIONS: This study suggests a beneficial role for GM-CSF in the malnourished host predisposed to infection. The antimicrobial properties of GM-CSF may function through enhanced production of nitric oxide and superoxide anion.

Animals↗

The effect of granulocyte-macrophage colony-stimulating factor on myeloid cells and its clinical applications.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a naturally occurring growth factor produced by several cell types in response to a variety of stimuli. GM-CSF has potent stimulatory effects on the growth and maturation of hematopoietic cells and has profound effects on mature circulating effector cells. Clinical applications of GM-CSF include ameliorating chemotherapy-induced neutropenia and enhancing hematopoietic recovery after bone marrow transplantation. This review evaluates the effect of GM-CSF on myeloid cells and its clinical applications.

Acquired Immunodeficiency Syndrome↗

Antigen presentation in protein-energy malnutrition.

Protein-energy malnutrition is associated with intrinsic defects in macrophage (MO) microbicidal function, but effects on MO-CD4+ cell interaction are unclear. This study examined the effect of protein-energy malnutrition on components of Ag presentation (AP) by peritoneal macrophages (PMO) and splenocyte responses (MLR) in the naive (resident) and infected state (mycobacterium-BCG), and assessed the potential role of prostaglandin (PGE2) and L-arginine-derived nitric oxide (NO) as regulatory mechanisms in these immune interactions. Mice were randomized to receive either a control (24% casein, RD) or low-protein (2.5% casein, LPD) diets for 8 weeks. PMO and splenocytes were harvested and AP function and MLR assessed +/- NG-mono-methyl-L-arginine (NMMA; competitive inhibitor of NO. synthesis) or indomethacin (PGE2 inhibitor). PMO components of AP were evaluated, including phagocytic function, MHC-class II (Ia) expression, and interleukin-1 (IL-1) and interleukin-6 (IL-6) production. PGE2 production and NO. (measured as NO-2) synthesis were also assessed. AP and MLR were preserved in protein-energy malnutrition in both resident and activated states. BCG infection in RD was associated with PMO activation as measured by increased O-2 and NO-2 release, but impaired AP and MLR responses. NMMA and indomethacin enhanced AP and MLR in RD groups only. Individual components of PMO AP (phagocytosis, IL-1 and IL-6 production) were defective during protein-energy malnutrition, as were NO-2 and PGE2 production. Thus, AP and MLR were preserved in LPD groups which may be related to a loss of prostaglandin- and L-arginine-mediated suppressor mechanisms.

Animals↗

Peritoneal and splenic macrophage functions in the tumor-bearing host.

In the tumor-bearing host, depression of cell-mediated immunity has been well-demonstrated, but little is known about alterations in macrophage functions. We hypothesized that the presence of a tumor may cause functional suppression of peritoneal macrophage and splenic macrophage functions, perhaps due to prostaglandin-E2 (PGE2) and nitric oxide. C57 BL/6 mice (n = 18) were injected subcutaneously with Lewis lung carcinoma 3 tumor. Control mice (n = 18) received no tumor and were pair-fed to intake of the tumor group. On Day 21, peritoneal and splenic macrophages were harvested. Cell surface Ia expression, cytotoxicity against P815 target cells, Candida albicans killing, and production of PGE2, nitric oxide, and superoxide were measured. Mean Ia expression was decreased in tumor animals for both peritoneal and splenic macrophages. In tumor animals PGE2 production significantly increased in both peritoneal and splenic macrophages. Superoxide production significantly decreased in peritoneal macrophages but significantly increased in splenic macrophages. Nitric oxide production was also significantly depressed in tumor-bearing host peritoneal macrophages. C. albicans killing was significantly depressed in tumor animals' peritoneal macrophages but showed little change in splenic macrophages. In tumor animals cytotoxicity was significantly decreased in peritoneal macrophages but significantly increased in splenic macrophages. In the tumor-bearing host, peritoneal macrophages have significantly decreased accessory and effector functions. Splenic macrophages demonstrate decreased accessory but enhanced effector functions. PGE2, superoxide, and nitric oxide appear to be important mechanisms of altered macrophage function in the tumor-bearing host; modifying their cellular production may enhance host defense.

Animals↗

Glucocorticoids mediate macrophage dysfunction in protein calorie malnutrition.

BACKGROUND: In hospitalized patients protein calorie malnutrition substantially increases the incidence of infection and death. Protein calorie malnutrition results in significant macrophage dysfunction. Whether a primary nutrient deficit or elevated glucocorticoids levels mediate this dysfunction is unclear. The aim of this study was to evaluate the neuroendocrine response to protein calorie malnutrition and its effects on macrophage function. METHODS: By use of a murine model of protein calorie malnutrition, mice were randomized to (1) a standard 24% casein diet (control), (2) protein-free diet (PFD), (3) PFD in adrenalectomized mice, (4) PFD plus the glucocorticoid receptor antagonist RU486 (10 mg/kg), or (5) a standard 24% casein diet plus a 50 mg corticosterone pellet implanted subcutaneously for 7 days. Mice were killed after 7 days, and body weight and serum albumin and corticosterone levels were measured. Peritoneal macrophages were obtained, and stimulated superoxide and interleukin-6 productions were measured. RESULTS: Protein calorie malnutrition significantly impaired macrophage function and elevated serum glucocorticoid levels. Blocking the stress corticosterone response with adrenalectomy or using RU486 to block corticosterone receptors prevented the impairment of macrophage function without restoring nutritional indexes (body weight and serum albumin level). Administration of glucocorticoids via a subcutaneous pellet reproduced macrophage impairment without leading to nutritional deficits. CONCLUSIONS: The neuroendocrine systemic response to protein calorie malnutrition with elevated serum corticosterone levels is a major determinant of macrophage dysfunction in protein calorie malnutrition.

Animal Nutritional Physiological Phenomena↗

Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients.

OBJECTIVE: The objective of this study was to evaluate long-term enteral nutrition support in postoperative cancer patients. BACKGROUND: Multimodality therapy for surgical patients with upper gastrointestinal malignancies may improve survival, but often results in substantial malnutrition, immunosuppression, and morbidity. The benefits of combined inpatient and outpatient enteral feeding with standard diets or diets supplemented with arginine, RNA + omega-3 fatty acids are unclear. METHODS: Sixty adult patients with esophageal (22), gastric (16), and pancreatic (22) lesions were stratified by disease site and percent usual weight and randomized to receive supplemental or standard diet via jejunostomy beginning on the first postoperative day (goal = 25 kcal/kg/day) until hospital discharge. Patients also were randomized to receive (n = 37) or not receive (n = 23) enteral jejunostomy feedings (1000 kcal/day overnight) for the 12- to 16-week recovery and radiation/chemotherapy periods. Plasma and peripheral white blood cells were obtained for fatty acid levels and PGE2 production measurements. RESULTS: Mean plasma and cellular omega 3/omega 6 fatty acid levels (percent composition) increased significantly (p < 0.05) in the arginine + omega-3 fatty acid group by postoperative day 7 (0.30 vs. 0.13) and (0.29 vs. 0.14) and continued to increase over time. Mean PGE2 production decreased significantly (p < 0.05) from 2760 to 1600 ng/10(6) cells/mL at day 7 in the arginine + omega-3 fatty acid group, whereas no significant change over time was noted in the standard group. Infectious/wound complications occurred in 10% of the supplemented group compared with 43% of the standard group (p < 0.05); mean length of hospital stay was 16 vs. 22 (p < 0.05) days, respectively. Of the patients who received postoperative chemoradiation therapy, only 1 (6%) of the 18 patients randomized to receive tube feeding did not continue, whereas 8 (61%) of the 13 patients not randomized to tube feedings required crossover to jejunostomy nutritional support. CONCLUSIONS: Supplemental enteral feeding significantly increased plasma and peripheral white blood cell omega 3/omega 6 ratios and significantly decreased PGE2 production and postoperative infectious/wound complications compared with standard enteral feeding. For outpatients receiving adjuvant therapy, those initially randomized to oral feedings alone required rehospitalization more frequently, and 61% crossed over to supplemental enteral feedings.

Aged↗

Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial.

OBJECTIVE: To determine if early enteral feeding, in an intensive care unit (ICU) patient population, using a formula supplemented with arginine, dietary nucleotides, and fish oil (Impact), results in a shorter hospital stay and a reduced frequency of infectious complications, when compared with feeding a common use enteral formula (Osmolite.HN). DESIGN: A prospective, randomized, double-blind, multicenter trial. SETTING: ICUs in eight different hospitals. PATIENTS: Of 326 patients enrolled in the study, 296 patients were eligible for analysis. They were admitted to the ICU after an event such as trauma, surgery, or sepsis, and met a risk assessment screen (Acute Physiology and Chronic Health Evaluation II [APACHE II] score of > or = 10, or a Therapeutic Intervention Scoring System score of > or = 20) and study eligibility requirements. Patients were stratified by age (< 60 or > or = 60 yrs of age) and disease (septic or systemic inflammatory response syndrome). INTERVENTIONS: Patients were enrolled and full-strength tube feedings were initiated within 48 hrs of the study entry event. Enteral feedings were advanced to a target volume of 60 mL/hr by 96 hrs of the event. One hundred sixty-eight patients were randomized to receive the experimental formula, and 158 patients were randomized to receive the common use control formula. MEASUREMENTS AND MAIN RESULTS: Both groups tolerated early enteral feeding well, and the frequency of tube feeding-related complications was low. There were no significant differences in nitrogen balance between groups on study days 4 and 7. Patients receiving the experimental formula had a significant (p = .0001) increase in plasma arginine and ornithine concentrations by study day 7. Plasma fatty acid profiles demonstrated higher concentrations of linoleic acid (p < .01) in the patients receiving the common use formula and higher concentrations of eicosapentaenoic and docosahexaenoic acid (p < .01) in the patients receiving the experimental formula. The mortality rate was not different between the groups and was significantly (p < .001) lower than predicted by the admission severity scores in both feeding groups. In patients who received at least 821 mL/day of the experimental formula, the hospital median length of stay was reduced by 8 days (p < .05). In patients stratified as septic, the median length of hospital stay was reduced by 10 days (p < .05), along with a major reduction in the frequency of acquired infections (p < .01) in the patients who received the experimental formula. In the septic subgroup fed at least 821 mL/day, the median length of stay was reduced by 11.5 days, along with a major reduction in acquired infections (both p < .05) in the patients who received the experimental formula. CONCLUSIONS: Early enteral feeding of the experimental formula was safe and well tolerated in ICU patients. In patients who received the experimental formula, particularly if they were septic on admission to the study, a substantial reduction in hospital length of stay was observed, along with a significant reduction in the frequency of acquired infections.

APACHE↗

Case study: maternal residual attention deficit disorder associated with failure to thrive in a two-month-old infant.

A male infant was admitted twice during his second month of life for failure to thrive. An extensive organic workup was unremarkable. During the second admission, the pediatric inpatient psychiatry team was consulted. Evaluation led to the diagnosis of residual attention deficit disorder in the mother. Inattention and impulsivity hampered mother's ability to feed the child. Successful treatment of mother's residual attention deficit disorder with methylphenidate led to significant improvement in the infant's feeding, subsequent weight gain, and observed maternal-child interaction.

Attention Deficit Disorder with Hyperactivity↗

Use of standardized nursing diagnoses and interventions in long-term care.

1. Standardized language for patient assessment, nursing diagnoses and interventions provide a common language for professionals in long-term care. 2. A comprehensive Nursing Interventions Classification (NIC) was first published in 1992 by the Iowa Intervention Project and the North American Nursing Diagnosis Association offers a comprehensive list of nursing diagnoses. 3. Most frequently used nursing diagnoses were: Self Care Deficit: Bathing/Hygiene, Self Care Deficit: Dressing/Grooming, Impaired Physical Mobility, Altered Thought Process, and Potential for Injury.

Female↗

Current indications for intravenous nutritional support in oncology patients.

No clear role has yet been defined for the role of total parenteral nutrition in the management of the cancer patient, and this subject remains an area of controversy. Peri-operative nutritional support, if given for at least 10 days, may reduce morbidity and mortality in some patients, although this subgroup has not been fully characterized. There is no evidence that parenteral nutritional support benefits patients undergoing chemotherapy or radiotherapy in terms of an increased tumor response rate or prolongation of survival.

Animals↗

What nursing diagnoses do nurses use in long term care?

The results of this survey validate that the NANDA nursing diagnoses classification is appropriate for use in long term care. Although ninety three percent of the current NANDA nursing diagnoses are used in practice, there remains a need for the development and testing of additional nursing diagnoses to describe patient problems encountered in long term care. Nurses in education and practice settings must work collaboratively to continue to identify, refine and validate the nursing diagnoses that are most appropriate for frail, older and/or chronically ill residents of long term care facilities.

Geriatric Nursing↗