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Biomedical subjects

J M Daly

Publications and source records attributed to J M Daly.

At least 19 recordsLinked to original sources
PubMed1992

Colorectal cancer. Principles of postoperative follow-up.

Monitoring patients after primary large bowel surgery for malignancy is predicated on the concept that early detection of recurrence may provide salvage treatment for cure. Knowledge of the pathologic site and stage provides important information as to the probability of recurrence and the patterns of failure that are likely to occur. Available methods to detect recurrence include clinical, roentgenographic, and serum tests that are done more frequently during the first 2 years after surgery. Monitoring plasma carcinoembryonic antigen levels can lead to identification of asymptomatic recurrences, but there is controversy about the curability of recurrences outside the liver. Newer techniques (such as computed tomographic portography, intraoperative ultrasonography, and radioimmunoguided surgery) provide greater diagnostic accuracy and lead to more appropriate procedures during "second-look" operations. For example, hepatic resection in properly selected patients offers up to a 30% chance of cure and should be pursued aggressively. A search for metachronous cancers by endoscopy also should be done. Knowledge of the potential and patterns of failure can provide a useful guide during the postoperative follow-up care of the patient with large bowel cancer.

Colorectal Neoplasms↗
PubMed1992

Growth-factor-independence and invasive properties of colorectal carcinoma cells.

During serial passage of the colorectal carcinoma cell line SW1116 in athymic nude mice, we selected 2 variants that metastasized to the lungs and liver. The metastatic capacity of these in vivo variant cell lines was associated with their ability to (1) grow under growth-factor-deprived conditions, (2) invade and transgress a reconstructed basement membrane with high effectiveness, and (3) produce higher activities of the substrate-degrading enzymes collagenase and plasminogen activator as compared to parental cells. To assess the relative contribution of growth-factor-independence and high levels of invasiveness/motility to the metastatic phenotype, variants of 6 colorectal carcinomas were selected in vitro by adaptation to a growth-factor-free culture medium followed by selection of highly invasive cells in chemoinvasion assays. Four out of 6 cell lines selected for growth-factor-independence showed significantly higher levels of invasiveness through reconstructed membranes, suggesting co-segregation of growth-factor-independence and high levels of invasiveness in vitro. Using an in vitro chemoinvasion assay, 2 poorly and 1 highly invasive cell line were further selected for invasiveness. After 6 selection passages, all cell lines were highly invasive and showed high motility rates. However, when injected s.c. into athymic nude mice to test their metastatic capacity in vivo, double-selected variant cell lines did not form spontaneous metastases. Our results indicate that growth-factor-independence and high levels of invasiveness, although associated with the metastatic phenotype, are not sufficient for experimental metastasis formation of colorectal carcinoma cells in vivo.

Animals↗
PubMed1992

Interleukin 1 and its relationship to endotoxin tolerance.

Endotoxin (lipopolysaccharide [LPS])-induced cytokine release has been implicated in the pathogenesis of sepsis. Sublethal doses of LPS induce tolerance to a septic insult. This study evaluated pretreatment with interleukin 1 (IL-1) against an LPS challenge and examined its relationship to endotoxin tolerance. C3H/HeN mice (N = 100) were injected intraperitoneally with phosphate-buffered saline (control group), IL-1 (200 micrograms/kg), or LPS (1 mg/kg) for 3 days. On day 5, peritoneal macrophages were harvested and assayed for antimicrobial activity (superoxide anion production and Candida albicans phagocytosis). Serum cytokine levels and survival after an LPS challenge on day 5 were also assessed. Pretreatment with IL-1 or LPS significantly increased superoxide anion production, C albicans phagocytosis, and survival compared with pretreatment with phosphate-buffered solution. Interleukin 6 levels significantly decreased in the IL-1 and LPS groups. Peak levels of tumor necrosis factor significantly decreased only in the LPS group. Thus, pretreatment with IL-1 or low doses of LPS may exert protective effects by decreasing levels of interleukin 6 while increasing antimicrobial activity. Mice pretreated with IL-1 were protected from endotoxin despite elevated peak levels of tumor necrosis factor, suggesting a different mechanism for endotoxin tolerance than for tolerance to tumor necrosis factor.

Animals↗
PubMed1992

Impairment of macrophage activation and granuloma formation by protein deprivation in mice.

Protein-calorie malnutrition predisposes to infection by intracellular pathogens, but the basis for this predisposition is unclear. We studied the effect of protein deprivation on mouse peritoneal macrophage function and on granuloma formation during infection by bacille Calmette-Gueŕin (BCG). Injection of lipopolysaccharide (LPS) to induce inflammation elicited fewer peritoneal cells from mice fed a 2.5% protein diet than from mice fed an isocaloric chow in which protein calories constituted 24% of the total. LPS-elicited macrophages from protein-deprived mice demonstrated a reduction in spreading, total cell protein, cell lactate dehydrogenase, and release of superoxide anion (O2-) in response to stimulation. Priming in vitro by interferon (IFN)-gamma for enhanced release of O2- was also significantly impaired in protein-deprived mice. This defect was reversible by repletion with 24% protein diet for 10 days. Impairment of macrophage function in protein-deprived mice was further evidenced by an impaired capacity to express Ia antigen in response to IFN-gamma and by reduced production of IL-1 activity in response to LPS. Infection by BCG in protein-deprived mice was characterized by impaired granuloma development in liver, lungs, and spleen. Thus, in this model, protein deprivation significantly impaired macrophage activation, as assessed by morphologic, metabolic, and functional criteria. This impairment might compromise immune effector mechanisms dependent on macrophage activation, including rejection of intracellular pathogens.

Animals↗
PubMed1992

Anti-neoplastic effects of interleukin-4.

Interleukin-4 (IL-4) is a cytokine, with potential anti-neoplastic effects. This study examined the effects of IL-4 on host anti-tumor responses in a murine model. C57/B16 mice (n = 40) were randomized to receive Lewis lung carcinoma (10(6) cells: right flank; sc) or saline, and sacrificed 10 days postinoculation for assessment of peritoneal macrophage (PMO) anti-tumor mechanisms [superoxide anion generation (O2-), tumor necrosis factor (TNF), and TNF-independent (P815) cytotoxicity], splenocyte mixed lymphocyte response (MLR) (Balb/c stimulator), and cytotoxic lymphocyte generation (CTL against P815). Cells were cultured +/- IL-4 (100 U/ml). In a second study, 20 mice received Lewis lung implants (sc) and were randomized on Day 21 to receive daily IL-4 (1000 U/mouse; ip) or saline. Tumor volumes and median survival were assessed. Tumor necrosis factor-independent cytotoxicity (O2-, MLR and CTL) was impaired in the tumor-bearing (TB) study group. Interleukin-4 administered to cultured cells from TB mice enhanced O2-, as well as MLR and CTL (P less than 0.01), and decreased TNF release but did not alter PM phi TNF-independent anti-tumor responses (P815). In vivo administration of IL-4 significantly decreased tumor growth (P less than 0.05) after 10 days of treatment and significantly prolonged median host survival (P less than 0.05). These findings indicate the therapeutic potential of IL-4 in the TB host which may function through downregulation of TNF production while potentiating certain T cell-dependent and independent anti-tumor immune mechanisms.

Animals↗
PubMed1992

The effect of fasting and cholecystokinin stimulation on normal and neoplastic tissue in the rat pancreas.

Pancreatic nodules were produced in rats by either feeding raw soya flour alone or by injection of azaserine plus raw soya flour feeding. The resulting nodules were studied to determine whether there was any functional difference between this tissue and the relatively normal internodular pancreas. Tissue DNA and trypsin content were significantly elevated in nodules compared to the adjacent tissue. With fasting, protein and enzyme content increased significantly and equally in both nodular and internodular tissues. RNA levels fell significantly and the decrease was more pronounced in nodular tissue. The responsiveness of the multinodular pancreas to cholecystokinin was examined by measuring pancreatic secretion basally and in response to cholecystokinin. Both the volume and protein content secreted by the multinodular pancreas were greatly elevated above control levels. When corrected for pancreatic weight, the difference remained significant and appeared to be due to increased basal secretion by the nodular pancreas. These studies demonstrate that azaserine-raw soya flour induced nodules are functionally efficient. Furthermore, the secretory response to cholecystokinin of these nodules is equal to or higher than that of normal tissue.

Amylases↗
PubMed1992

Loco-regional nodal relapse in melanoma.

Two-hundred and seven patients without evidence of disease following lymph node dissection (LND) were stratified into three groups: Group A, lymph node relapse within the site of prior LND; Group B, lymph node relapse in a different, but regional, lymph node group; Group C, no lymph node relapse. Decreased survival was noted in both Groups A and B versus Group C. Prognostic factors were identified as: (i) axial or subungal/volar (subvolar) location and the number of positive lymph nodes at initial LND for nodal relapse within the same lymph node group; (ii) male gender, axial/subvolar location, and the number of histologically positive lymph nodes at initial LND for nodal relapse in a different, but regional lymph node group; (iii) relapse within the initial LND site for a decreased survival. Six of 10 patients with both axial/subvolar primaries and four or more positive lymph nodes developed a relapse within the dissection site post-LND. These prognostic factors describe a subset of patients who would be candidates for postoperative adjuvant local/regional and systemic therapy trials.

Adolescent↗
PubMed1992

Use of radiolabelled monoclonal antibodies in patients with primary and metastatic large bowel cancer.

Accurate assessment of the extent of primary and metastatic large bowel cancer is critical to surgical decision making and to providing reliable prognostic information. This prospective study compared external gamma camera images and an intraoperative hand-held gamma detecting probe for detection of radiolabelled monoclonal antibody (B72.3) in 28 patients with primary and metastatic large bowel cancer. Fourteen patients received 0.2 to 20 mg (2 or 5 mCi) 111indium-labelled monoclonal antibody B72.3 followed by whole body imaging scan with an external gamma detector/camera on two occasions 24 h apart within 7 days after injection. Fourteen patients received 1.0 mg (2.0 mCi) 125iodine-B72.3 followed by intraoperative probe evaluation 2-3 weeks postinjection. Mean patient ages for the two groups were 60 years (range 28-75 years) and 63 years (range 43-77 years), respectively. Disease sites were primary in the large bowel in six patients and primary as well as metastatic in 22 patients. External scanning detected 111indium-B72.3 uptake in 1/5 primary lesions, 1/7 hepatic and 1/3 extrahepatic sites. The intraoperative gamma probe localized disease in 1/3 primary lesions, 7/11 hepatic and 3/3 extrahepatic sites. The intraoperative gamma probe had a sensitivity of 71% for detection of metastases compared with a 20% sensitivity using the external gamma scan method (P = 0.03). 125iodine-labelled B72.3 influenced the extent of the operative procedure in 4/14 (29%) patients; immunolocalization with external gamma detection did not alter the operative procedure in the 14 patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

Azaserine-induced pancreatic foci: detection, growth, labelling index and response to raw soya flour.

Atypical acinar cell foci were induced in the pancreases of rats by injection of azaserine. An incubation period of 6 weeks was sufficient for the detection of all glutathione S-transferase mu positive foci. In chow-fed rats, the labelling index of foci was 12-fold higher than normal pancreatic tissue. Feeding rats raw soya flour (RSF) for up to 20 weeks did not increase the number of foci per pancreas but did produce significant increases in labelling index and growth rate. In normal pancreatic tissue, the trophic response was complete after 4 weeks of RSF feeding. In foci, however, the trophic response to RSF was prolonged. Involution of normal pancreatic tissue was seen in rats fed RSF for 19 weeks and then switched to chow 1 week prior to death. No evidence for involution was seen in the foci of these animals, although a 40-fold reduction was seen in labelling index. The labelling index of these foci was reduced to the level seen in normal tissue of chow-fed rats. These results are consistent with increased cholecystokinin (CCK) responsiveness and CCK dependence in azaserine-induced pancreatic foci.

Animals↗
PubMed1992

Enhancement of interleukin-2 immunotherapy with L-arginine.

Nutrient substrates have been shown to enhance cell-mediated immunity, but their role as adjuvants to immunotherapy has not been previously determined. This study evaluated L-arginine as an essential substrate for optimal generation of lymphokine-activated killer (LAK) cells. This experiment also assessed supplemental dietary L-arginine as a means to potentiate the host antitumor response to interleukin-2 (IL-2) in a murine neuroblastoma (NRB) model. A/J mice received 1% arginine or isonitrogenous 1.7% glycine in addition to a regular diet 14 days before subcutaneous inoculation with C1300 NRB cells. Twenty-four hours later, animals received low (1 x 10(6) U/kg three times a day) or high (3 x 10(6) U/kg three times a day) doses of IL-2 or saline intraperitoneally for 4 days. On days 4 and 10 post-C1300 NRB inoculation, mice were killed for assessment of natural killer cell and tumor specific cytotoxicity. Remaining animals were followed for tumor incidence, tumor growth, and duration of host survival. Interleukin-2 therapy in mice receiving dietary arginine compared with those receiving glycine resulted in significantly augmented natural killer cell cytotoxicity (day 4) and generation of specific tumoricidal mechanisms (day 10). The addition of dietary arginine to low-dose IL-2 therapy significantly diminished C1300 NRB engraftment (p less than 0.05) and growth (p less than 0.001) and prolonged the duration of host survival (p less than 0.05) compared with the glycine treatment group. In vitro studies demonstrated that L-arginine is an essential substrate for optimal generation of LAK cells. Thus, supplemental dietary L-arginine enhances lymphocyte cytotoxic mechanisms and potentiates IL-2 immunotherapy.

Amino Acids↗
PubMed1992

Injection sites utilized for DPT immunizations in infants.

The purpose of this investigation was to determine the site utilized by nurses for administering Diphtheria and Tetanus Toxoids and Pertussis (DPT) injections to infants under 7 months of age. Twenty-six of the 28 agencies identified in a metropolitan area as administering DPT injections chose to participate in the study. Those individuals administering DPT injections in the agencies completed a questionnaire with a return rate of 69% (n = 55). Forty-four participants indicated that they used the anterolateral thigh, the recommended site, 100% of the time. The participants in the study administered a total of 1,453 DPT injections per month. Eighty-seven percent of those injections were administered in the anterolateral thigh, 3.6% were given in the deltoid, 5.1% were given in the dorsal gluteal, and 4% were given in the ventrogluteal. The estimated proportion of DPT injections administered at the correct site was 84.65% which is much lower than the critical value 94.06% for alpha = .05 (p less than .00001).

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed1992

Scholarship and socialization: reflections on the first year of doctoral study.

The first year of study in our PhD program has both broadened and intensified our knowledge. We have come to expect ourselves to attain better understandings of any given issue or topic within its attendant context and within the larger context of our profession. We have begun to appreciate and to strive for the clarity, thoroughness, and precision of thought and analysis that typify the nurse scholar. We are beginning to recognize who the nurse scholar is, why we want to emulate this person, and how we can become this person. As members of the fourth generation, we are now beginning, through our doctoral program, to live the vision of scholars who preceded us. To fulfill this vision, we understand that learning is a lifelong process that does not end with achievement of the doctorate or with postdoctoral study, but that it is continually evolving. We recognize the crucial role of research in nursing, but temper this recognition with the knowledge that research must progress in a planned manner dovetailing with existing research lest it fail to strengthen the web of nursing knowledge.

Education, Nursing, Graduate↗
PubMed1992

Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome.

The individual nutrients arginine, RNA, and omega-3 fatty acids improve immune function, but prospective trials have not demonstrated their effects on clinical outcome. Patients (n = 85) who underwent operation for upper gastrointestinal malignancies were randomized to receive the supplemental diet or a standard enteral diet after surgery. Clinical patient characteristics were similar between the two groups. Mean caloric intakes (1421 vs 1285 kcal/day) were similar between groups. Mean nitrogen intakes (15.6 vs 9.0 gm/day) and nitrogen balances (-2.2 vs -6.6 gm/day) measured in the first 20 patients were significantly greater in the supplemented group than in the standard group (p = 0.05). In vitro lymphocyte mitogenesis was measured in the first 31 patients and was decreased on postoperative day 1 in both groups, but normal levels were regained only in the supplemented group. In the cohort of 77 eligible patients, infectious and wound complications occurred significantly less often (11% vs 37%) in the supplemented group than in the standard group (p = 0.02). Linear logistic models for infectious/wound complications with control for the amount of nitrogen suggested (p = 0.10) dietary treatment as the major factor. Mean length of stay in the hospital was significantly shorter (p = 0.01) for the supplemented group (15.8 +/- 5.1 days) than for the standard group (20.2 +/- 9.4 days). These results suggest that postoperative enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids instead of a standard enteral diet significantly improved immunologic, metabolic, and clinical outcomes in patients with upper gastrointestinal malignancies who were undergoing major elective surgery.

Aged↗
PubMed1992

Effects of laparotomy on systemic macrophage function.

Surgical trauma induces immunosuppression that may adversely influence survival. This study examined the effect of laparotomy on two different macrophage populations, peritoneal macrophages (PM phi) and Kupffer cells. Female, 6- to 8-week old, CFW/C3H-HeN mice (n = 160) were randomly allocated to one of three study groups: control, ether anesthetic only, or ether anesthetic and laparotomy. On postoperative days 1 and 3, PM phis and Kupffer cells were harvested and assayed for superoxide anion production (O2-), percent macrophage phagocytosis of Candida albicans (CAP), percent C. albicans killed by macrophages (CAK), percent major histocompatibility complex (MHC)-class II antigen expression, and antigen presentation. Macrophages isolated on postoperative day 1 were also cocultured with 100 units/10(6) cells/ml interferon-gamma (IFN-gamma). Laparotomy significantly impaired microbicidal activity (O2-, percent CAP, and percent CAK) and antigen presentation on postoperative day 1. On postoperative day 3, O2- and antigen presentation were increased significantly (p less than 0.05) over control values, indicating a rebound phenomenon. Kupffer cell microbicidal function was unchanged on postoperative days 1 and 3. The initial immune impairment (PM phis: O2-, CAP, and CAK) was abrogated by IFN-gamma treatment. In immunosuppressed hosts after injury, administration of macrophage-activating factors such as IFN-gamma could be of therapeutic benefit.

Animals↗
PubMed1991

Integrated magnetic resonance imaging and phosphorus spectroscopy of soft tissue tumors.

Eighteen patients with soft tissue masses underwent integrated magnetic resonance imaging (MRI) and phosphorus spectroscopy (31P-MRS) to evaluate benign and malignant tumor morphology and metabolism. Spectra from soft tissue tumors had a significantly higher proportion of phosphate in the low-energy portion of the 31P spectrum (P less than 0.001) with a concomitant decrease in phosphocreatine (P less than 0.01) compared with 31P spectra from normal muscle. Malignant tumors had a mean pH of 7.35 +/- 0.13 which was greater than that of muscle tissue with a mean pH of 7.08 +/- 0.07 (P less than 0.001). All tumors had greater relative levels of phosphomonoesters, inorganic phosphate, and phosphodiesters compared with those in muscle tissue but considerable variability among tumors was noted due to tumor size, extent of tumor necrosis, and muscle contamination. Integrated MRI/MRS studies are necessary to provide exact localization of the tumor and a more correct interpretation of the 31P-MRS data.

Adolescent↗
PubMed1991

Impaired macrophage function in severe protein-energy malnutrition.

Protein-energy malnutrition induces immunosuppression that predisposes to sepsis, but the mechanisms are unclear. This study examines the role of the macrophage in host defense in the malnourished state. Swiss-Webster mice (N = 300) were randomly allocated to control (24% casein) or low-protein (2.5% casein) diets for 8 weeks. We studied the ability of two populations of macrophages, peritoneal macrophages, and Kupffer cells to produce superoxide anion after in vivo administration of endotoxin or mycobacterium (bacille Calmette-Guérin). Phorbol diester and Candida albicans were used as stimuli. In another group of mice, we evaluated the ability of interferon gamma to up-regulate superoxide anion release and Candida phagocytosis and killing. Mice under protein-energy malnutrition demonstrated decreased mean body weights, serum protein levels, and cell yields. Superoxide anion production in resident and activated (lipopolysaccharide, interferon gamma, bacille Calmette-Guérin infection) peritoneal macrophages was significantly reduced in the malnourished group. Candida phagocytosis and killing were also both depressed in malnourished mice. Kupffer cells failed to generate superoxide anion in all groups. We conclude that severe protein-energy malnutrition significantly impairs macrophage function, which could diminish response to acute and chronic septic challenges. Interferon gamma up regulated peritoneal macrophage and Kupffer cell microbicidal function, which suggests a therapeutic role for this lymphokine in the malnourished septic host.

Animals↗