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Biomedical subjects

J M Daly

Publications and source records attributed to J M Daly.

At least 91 records · Page 5Linked to original sources

Small bowel necrosis associated with postoperative jejunal tube feeding.

BACKGROUND: Postoperative enteral nutrition using jejunal tube feeding is widely practiced and usually well tolerated. Functional intestinal complaints occur frequently but generally respond to alteration of the infusion rate or tube feeding formula. Occasionally, however, nonspecific signs of intestinal disturbance progress to a syndrome of abdominal distention, hypotension, and hypovolemic shock resulting in extensive small bowel necrosis. STUDY DESIGN: During a six-year period, four patients have been identified retrospectively who had this complication among 1,359 patients receiving jejunal tube feeding. Their clinical course was evaluated critically and compared with 11 cases described in the literature. RESULTS: Small bowel necrosis is a rare but highly morbid complication associated with postoperative jejunal tube feeding. Of 14 patients who had small bowel necrosis develop, 12 succumbed to this complication. The causative mechanism remains unclear, but is most likely the result of several factors. CONCLUSIONS: Tube feeding should be discontinued immediately and total parenteral nutrition should be considered in patients who have abdominal pain, abdominal distention, increased nasogastric drainage, and signs of intestinal ileus.

Adult↗

Inhibition of nitric oxide synthesis is detrimental during endotoxemia.

BACKGROUND: Increased production of nitric oxide has been implicated as a mediator during septic shock and sepsis syndrome. Inhibition of nitric oxide production could be beneficial during endotoxemia to improve the individual's hemodynamic status and possibly outcome. OBJECTIVE: To evaluate the effects of nitric oxide inhibition on macrophage function and survival in a murine sepsis model. DESIGN: Sixty-eight female Swiss-Webster (ND4) mice were injected with a sublethal dose of Escherichia coli lipopolysaccharide (25 mg/kg). INTERVENTION: The treated group (n = 34) received 10 mg/kg of NG-nitro-L-arginine methyl ester at the time of lipopolysaccharide injection. MAIN OUTCOME MEASURES: Blood samples and peritoneal macrophages were obtained at baseline and at 2, 4, and 8 hours after injection. Nitrite levels were measured in 36 mice from plasma and supernatant samples of cultured peritoneal macrophages stimulated with interferon gamma (100 micrograms/mL) for 48 hours. Thirty-two animals were observed for survival. RESULTS: Administration of N-nitro-L-arginine methyl ester after lipopolysaccharide injection caused significant reductions in macrophage mean nitrite production from 13 and 15 mumol/L to 7 and 11 mumol/L (P < .05) and reduced mean plasma nitrite concentrations from 100 and 118 mumol/L to 46 and 108 mumol/L (P < .05) at 2 and 4 hours, respectively. The rate of survival was significantly decreased to 0% in the group receiving N-nitro-L-arginine methyl ester after septic challenge compared with 87.5% in controls (P < .005). CONCLUSIONS: Inhibition of nitric oxide production is detrimental in this murine model of endotoxemia.

Animals↗

Glucocorticoid receptor blockade reverses postinjury macrophage suppression.

OBJECTIVES: To study the effects of the stress-induced surge of endogenous glucocorticoids on macrophage function and the role of inhibiting glucocorticoids with a receptor antagonist, mifepristone (RU 486). DESIGN: One hundred thirty female Swiss-Webster mice were randomly assigned to either injury by femur fracture or uninjured anesthesia control in this intervention study. SETTING: A university-based surgical laboratory and animal facility. INTERVENTION: Injured mice were randomized to receive either the glucocorticoid receptor antagonist mifepristone (10 mg/kg by oral gavage) or its vehicle. Mifepristone or its vehicle were given either 2 hours before or 2 hours after the injury. MAIN OUTCOME MEASURES: Peritoneal macrophages were harvested 24 hours after the injury. Macrophages were assayed for the stimulated (phorbol myristate acetate, 1 microgram/mL) production of superoxide anion, secretion of interleukin-6, tumor necrosis factor alpha, and prostaglandin E2 in response to endotoxin (lipopolysaccharide at 10 micrograms/mL) and killing of Candida albicans. RESULTS: Pretreatment with mifepristone significantly prevented or reduced suppression of several macrophage functions following injury, including superoxide production and C albicans killing. Treatment after the injury preserved only C albicans. Mifepristone failed to block the increased secretion of prostaglandin E2 after injury. CONCLUSION: Pretreatment with mifepristone before an injury prevented suppression of several macrophage functions. Further studies are required on the effects of glucocorticoid inhibition on other aspects of the immune and metabolic responses to injury to define the potential clinical applications of mifepristone trauma.

Administration, Oral↗

Alterations in macrophage signal transduction pathways mediate post-traumatic changes in macrophage function.

After injury, macrophage effector function diminishes while suppressor function increases. Protein kinase C (PKC), which initiates superoxide synthesis and phagocytosis, and phospholipase A2 (PLA2), which initiates eicosanoid metabolism, are key enzymes in cell signal transduction, which may mediate this change in cell function. The aim of this study was to investigate the effect of trauma on macrophage signal transduction. Swiss-Webster (CFW) mice (n = 210) were randomized to control or hindlimb amputation groups. Animals were sacrificed 24 hr after injury. Peritoneal macrophage function was assessed by measurement of superoxide anion (O2-), Fc, mannose-fucose-mediated phagocytosis, and PGE2 release. Membrane and cytosolic PKC activity were measured by radioimmunoassay in unstimulated and phorbol ester-stimulated cells. Membrane fatty acids and PLA2 activity were measured by thin-layer chromatography. Hindlimb amputation resulted in significantly decreased superoxide anion synthesis (0.7 +/- 0.2 nm vs 1.7 +/- 0.3 nmol/l/10(6) cells in controls, P < 0.01) and phagocytosis and a significant increase in prostaglandin E2 synthesis. This was associated with a shift in cell membrane metabolism with increased PLA2 activity, arachidonic acid turnover, and a significant reduction in PKC membrane translocation in response to phorbol ester. Together these data demonstrate an alteration in signal transduction pathways, which may account for the observed change in macrophage function after injury.

Amputation, Surgical↗

Total parenteral nutrition, bacterial translocation, and host immune function.

Total parenteral nutrition (TPN) is associated with increased infectious complications in trauma and perioperative patients compared with enteral nutrition support. This study evaluated the effects of TPN on splenocyte and peritoneal macrophage (PM phi) function and intestinal bacterial translocation. Male Wistar rats underwent central vein cannulation and were randomized to isocaloric feeding of a regular chow diet (RD) plus saline infusion or TPN for 7 days. Splenocytes and PM phi were harvested to assess concanavalin A mitogenesis, superoxide production, and Candida albicans phagocytosis. Bacteria-positive mesenteric lymph nodes (MLNs) were found in 77% (10 of 13) of TPN-fed rats compared with 17% (2 of 12) of RD-fed rats (p < 0.05). Splenocyte mitogenesis, PM phi superoxide production, and C. albicans phagocytosis were significantly decreased in the TPN group compared with results in the RD group. In a second study, rats received RD, TPN, and parenteral nutrition (PN) with 10% or 20% of calories given as oral chow (PN and 10% chow and PN and 20% chow) for 7 days. PN and 10% chow reversed the TPN-induced suppression of C. albicans phagocytosis. PN + 20% chow significantly increased splenocyte mitogenesis, PM phi superoxide production, and C. albicans phagocytosis and killing to normal levels and was associated with a decreased incidence of bacteria-positive MLN. Thus, administration of TPN is associated with impaired PM phi microbicidal and splenocyte proliferative function. These defective cellular functions were reversed with a small amount of oral feeding.

Animals↗

Villous adenoma of the main pancreatic duct: a clue to the pathogenesis of pancreatic malignancy.

We describe the case of a 78 year old woman with a severely dysplastic villous adenoma of the duct of Wirsung presenting with abdominal pain, emesis, weight loss, and hyperamylasemia. Abdominal ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography suggested an intraductal lesion in the head of the pancreas with a dilated distal duct. The patient underwent uncomplicated pancreaticoduodenectomy and has done well. A review of the literature on benign and malignant neoplasms of the main pancreatic duct allows formulation of the typical clinical syndrome, appropriate diagnostic work-up, treatment, and prognosis of patients with these rare lesions. The pancreatic ductal epithelium can present the full spectrum of lesions along the pathogenetic route to malignancy. This is evidence for the presence of an adenoma-to-carcinoma sequence in the pancreas analogous to that which exists in the colon.

Adenoma, Villous↗

Impairment of pulmonary macrophage function with total parenteral nutrition.

OBJECTIVE: The effects of total parenteral nutrition (TPN) administration on pulmonary macrophage function and host response to gram-negative pulmonary infection were evaluated. SUMMARY BACKGROUND DATA: Administration of TPN resulted in increased infectious complications in traumatized and perioperative patients, but underlying mechanisms are unclear. METHODS: Twenty-six male Wistar rats underwent central vein cannulation and were randomized to isocaloric feeding of a regular chow diet (RD) plus saline infusion or TPN without chow diet for 7 days. Pulmonary alveolar macrophage (PAM phi) superoxide production, Candida albicans phagocytosis and killing, and tumor necrosis factor (TNF) production in response to endotoxin (LPS) were assessed. Mesenteric lymph nodes (MLN) were cultured. A second group of rats (n = 6/group) were inoculated intratracheally with a sublethal dose of 9 x 10(9) live Escherichia coli per animal, and the lungs were cultured quantitatively 72 hours later to assess bacterial clearance. Finally, 11 RD-fed rats and 13 TPN-fed rats received intratracheal inoculation of 1.4 x 10(10) live E. coli and were included in follow-up. RESULTS: Administration of TPN was associated with a significant increase in bacteria positive MLN compared with those in the RD group (p < 0.01). Pulmonary alveolar macrophage superoxide production, Candida albicans phagocytosis and killing, TNF production, and pulmonary clearance of bacteria were decreased significantly in TPN-fed rats compared with those fed a regular chow diet (p < 0.05). These pulmonary macrophage function changes were associated with a significantly higher mortality in TPN-fed rats compared with RD-fed rats after higher dose pulmonary E. coli inoculation. CONCLUSIONS: Defective host pulmonary antimicrobial immune responses during TPN are associated with intestinal bacterial translocation, and may explain increased infectious complications.

Animals↗

The effect of teaching via telecommunications: a comparison of the academic performance of RN-BSN students in satellite centers and on campus.

The overall success of the delivery of courses in the nursing major via telecommunication requires careful planning and coordination among the on-campus course faculty, satellite area faculty facilitators, the personnel responsible for the technology, and contact persons in satellite areas responsible for classroom scheduling. Maintaining satellite programs for RN students is a project that requires ongoing evaluation.

Education, Nursing, Baccalaureate↗

Intestinal microbial translocation: immunologic consequences and effects of interleukin-4.

BACKGROUND: Administration of a chemically defined, liquid, elemental diet (CDD) results in intestinal microbial translocation, but the immunologic consequences of this process are unclear. This study evaluated the effects of CDD feeding and interleukin-4 (IL-4) administration on mesenteric lymphocyte, peritoneal macrophage (PMO), and hepatic Kupffer cell (KC) functions. METHODS: BALB/C mice (n = 60) were randomized to receive a paired feeding of regular diet (RD) or a CDD for 14 days. Mesenteric lymph nodes (MLN) and cecum were cultured for bacteria. Mixed lymphocyte response and cytotoxic T-lymphocyte function of MLN lymphocytes were assayed. PMO and KC were harvested to measure tumor necrosis factor production, macrophage binding of fluorescent-labeled lipopolysaccharide, and Candida albicans phagocytosis (CAP) and killing (CAK); KC-hepatocyte interaction was assessed by hepatocyte protein synthesis. In a second study 75 BALB/c mice received RD, CDD, and CDD+IL-4 (30,000 units/mouse intraperitoneally). MLN lymphocyte and PMO functions were measured and intestinal immunoglobulin A levels were determined. RESULTS: Oral feeding of a CDD resulted in significant impairment of mesenteric lymphocyte mixed lymphocyte response and cytotoxic T-lymphocyte functions and decreased PMO tumor necrosis factor production, fluorescent-labeled lipopolysaccharide binding, CAP, and CAK. KC function was preserved in CDD-fed mice. Administration of IL-4 significantly reduced the incidence of bacteria positive MLN and increased PMO superoxide production, CAP, CAK, and MLN lymphocyte mitogenesis. CONCLUSIONS: Use of IL-4 may be beneficial in situations where intestinal microbial translocation contributes to sepsis.

Animals↗

The effect of dietary protein depletion on hepatic 5-fluorouracil metabolism.

BACKGROUND: Protein calorie malnutrition, which is highly prevalent in tumor-bearing hosts, increases toxicity to 5-fluorouracil (5-FU), but the mechanisms are unclear. This study investigated the effects of protein depletion on 5-FU in vivo hepatic metabolism using F19-nuclear magnetic resonance spectroscopy (19F-NMRS). METHODS: Rats received normal (21.5%) or low (2.5%) protein diet for 25 days. 5-FU was injected intraperitoneally, and hepatic fluorine spectra were obtained. Parallel experiments were conducted to determine serum 5-FU pharmacokinetics using high-performance liquid chromatography (HPLC) and to measure hepatic dihydropyrimidine dehydrogenase (DPD) activity. RESULTS: The mean time of initial detection of fluoro-beta-alanine and the mean duration of the 5-FU signal in the liver were significantly prolonged in the low-protein group. 5-FU clearance and hepatic DPD activity were significantly lower in the low-protein group. Low-protein animals demonstrated increased toxicity, with diarrhea, weight loss, leukopenia (P < 0.001), and an 85% mortality, compared with regular diet animals, who had mild diarrhea and weight loss but no leukopenia and a 12% mortality. CONCLUSION: Protein depletion results in increased toxicity to 5-FU, which is associated with a significantly decreased rate of hepatic metabolism and clearance of 5-FU and a significant decrease in hepatic DPD activity. 19F-NMRS can noninvasively identify these alterations of 5-FU metabolism in vivo and may serve as a useful guide to determining chemotherapy dosage adjustments to reduce toxicity.

Animals↗

Macrophage-dependent candidacidal mechanisms in the murine system. Comparison of murine Kupffer cell and peritoneal macrophage candidacidal mechanisms.

Candida albicans infection is common in immunocompromised patients. The role of fixed tissue macrophages (M phi), including Kupffer cells (KC) and peritoneal macrophages (PM phi), in host defense against C. albicans is unclear. This study examined murine M phi candidacidal mechanisms and evaluated the in vitro role of the macrophage-activating factor IFN-gamma in augmenting these mechanisms. The effect of in vivo administration of IFN-gamma on survival after lethal C. albicans challenge in the murine system was also assessed. Percent PM phi and KC ingestion of C. albicans were similar. Prior opsonization of Candida increased the percentage of M phi ingestion of this pathogen. PM phi and KC phagocytic function was similar for both nonopsonized and opsonized C. albicans, but KC demonstrated markedly decreased ability to kill this pathogen (O2-, Candida killing). IFN-gamma enhanced KC and PM phi candidacidal activity. PM phi and KC Ag presentation was increased in early Candida infection, but diminished in established infection, when the majority of animals died. C. albicans failed to elicit significant amounts of either IL-1 or TNF compared with LPS stimulation of PM phi and KC in vitro. IFN-gamma treatment in vivo was associated with significantly improved survival (p < 0.01).

Animals↗

Enteroenteric intussusception due to a metastatic malignant fibrous histiocytoma.

Intussusception secondary to metastatic sarcoma is an unusual cause of small bowel obstruction. When a patient who has no history of a previous laparotomy, and has a known malignancy which metastasized hematogenously, presents with small bowel obstruction, the diagnosis of intussusception should be considered. The patient should be evaluated and treated accordingly.

Female↗

Genetic and antigenic analysis of an equine influenza H 3 isolate from the 1989 epidemic.

The haemagglutinin (HA) gene from the equine influenza H3N8 isolate Suffolk/89 has been cloned by reverse transcription and polymerase chain reaction amplification. The nucleotide sequence of the HA gene was determined from two independently cloned copies of the gene and was found to be most closely related to recent American isolates supporting the idea that most isolates of equine H3N8 are evolving as a single lineage. When the predicted amino acid sequence of the Suffolk/89 HA was examined, changes had taken place in at least four of the major antigenic sites, A, B, C, and D when compared to the sequences of the isolates used in the current vaccines (Miami/63 and Fontainebleau/79). Surprisingly, when the Suffolk/89 isolate was tested in haemagglutination inhibition (HI) assays with a panel of six mouse monoclonal antibodies, no differences were observed between the Suffolk/89 and the Fontainebleau/79 isolates, suggesting that this panel of monoclonal antibodies may recognise a limited subset of the major antigenic sites. Three anti-HA horse heterohybridoma monoclonals were able to distinguish between the Suffolk/89 and Fontainebleau/79 viruses, demonstrating that the horse does recognise these isolates as being antigenically different. The results of the work suggest that the isolates used in current equine influenza vaccines may need updating.

Amino Acid Sequence↗

Malnutrition, injury, and the host immune response: nutrient substitution.

Improvements in surgical management and intensive care therapy have enabled many patients to initially survive severe life-threatening trauma or major surgical procedures only to die after delayed bouts of sepsis. This paper reviews literature published within the past year on the effects of nutrient substitution on malnutrition, injury, and the host immune response. Topics discussed include immunodeficiencies in trauma and malnutrition, immunomodulation by nutrition, and parenteral versus enteral nutrition. We also discuss the roles of arginine, glutamine, omega-3 fatty acids, and dietary nucleotides in the host immune response.

Arginine↗

Diagnosis and management of distant recurrence in soft-tissue sarcomas.

Understanding of the patterns of, and treatments for, metastatic disease from soft-tissue sarcoma is of vital importance in caring for these patients. Metastasis can occur independently of adequate local control. When metastasis occurs, it usually causes no symptoms. Thus, all patients with malignant soft-tissue sarcomas must be followed with a careful surveillance regimen. When metastasis is discovered, the overriding goals of surgical treatment must be total resection of all tumor with the minimal loss of functional lung tissue. Multiple subsequent resections may be needed for recurrent metastasis but the goals remain the same. Postoperative chemotherapy may be of benefit in eradicating residual micrometastases. With ongoing research and the advent of more effective and better-tolerated adjuvant therapies, we should continue to make progress obtaining better cure rates and longer duration of survival for these patients.

Bone Neoplasms↗

Role of bactericidal permeability-increasing protein in the treatment of gram-negative pneumonia.

BACKGROUND: Gram-negative infections are a major cause of morbidity and death. Bactericidal permeability-increasing protein (BPI) is an endotoxin-neutralizing protein that also exhibits potent bactericidal activity. This study compared the efficacy of a 23 kd recombinant N-terminal fragment of BPI (rBPI23) with that of antiendotoxin antibody E5 in a model of gram-negative sepsis. METHODS: Sixty Swiss-Webster mice (Carworth farm) received an intratracheal inoculation of Escherichia coli (7 x 10(6) colony-forming units) and were randomized to three groups (20 per group). Starting immediately after inoculation, the groups received either rBPI23 (4 mg/kg intravenously every 2 hours for four doses), E5 (11 mg/kg intravenously every 24 hours for two doses), or an isotype control antibody B55 (11 mg/kg intravenously every 24 hours for two doses) and were followed up for survival. In a second survival study, 40 mice received the same intratracheal inoculation of E. coli and were randomized to two groups. Starting 2 hours after inoculation, the groups received either rBPI23 (4 mg/kg intravenously every 2 hours for four doses) or E5 (8 mg/kg intravenously every 12 hours for four doses) and were followed up for survival. In a third study, mice received an intratracheal inoculation of 3 x 10(6) colony-forming units E. coli, a sublethal dose, and were killed to determine pulmonary and blood clearance of bacteria. RESULTS: rBPI23 conferred significantly greater protection from death than either E5 or B55 when started immediately (95% survival vs 20% and 10%, respectively; p < 0.001) or 2 hours after inoculation (65% survival vs 25% for E5; p < 0.05). Both pulmonary and vascular clearance of bacteria was enhanced significantly by treatment with rBPI23. CONCLUSIONS: rBPI23 may be a novel therapeutic agent in the management of gram-negative sepsis.

Animals↗

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↗