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Biomedical subjects

A D Hill

Publications and source records attributed to A D Hill.

At least 19 recordsLinked to original sources
PubMed1996

Granulocyte-macrophage colony-stimulating factor inhibits tumor growth during the postoperative period.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) may have important antineoplastic properties because it induces macrophage tumoricidal activity in vitro. We examined the inhibitory effect of GM-CSF on tumor growth in a murine carcinoma model and whether this inhibitory effect would persist during the postoperative period. Potential macrophage-mediated mechanisms were studied. METHODS: The effect of GM-CSF on macrophage function in vitro was assessed by measuring superoxide anion and interleukin-6 production, percentage phagocytosis of Candida albicans, and percentage Ia expression. GM-CSF's effect on tumor volume was assessed first in a murine tumor model and second to examine whether these effects also occurred during the postoperative period in the same model after laparotomy. Macrophage function in the latter study was assessed by measuring superoxide anion, cytotoxicity, and tumor necrosis factor production. RESULTS: GM-CSF treatment was associated with a decrease in tumor volume on day 4 after the initiation of GM-CSF treatment (0.93 +/- 0.08 cm3 for control versus 0.34 +/- 0.08 cm3 for GM-CSF; p < 0.05). This effect was also seen after laparotomy (1.07 +/- 0.2 cm3 for laparotomy+saline versus 0.16 +/- 0.04 cm3 for laparotomy+GM-CSF, p < 0.05). In vivo macrophage function showed increased superoxide anion, cytotoxicity, and tumor necrosis factor-alpha production from macrophages obtained from GM-CSF treated animals compared with saline treated controls. CONCLUSIONS: Tumor growth is inhibited by GM-CSF treatment, and this effect also occurs after laparotomy. Thus, GM-CSF may have a therapeutic role in the treatment of the tumor bearing host after operation.

Analysis of Variance↗
PubMed1995

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↗
PubMed1995

Laparoscopic colonic surgery.

Laparoscopic surgical techniques have recently entered the field of colorectal surgery. Because the laparoscopic approach has revolutionized biliary surgery, it is hoped that similar advances will be possible in the more elderly population with colorectal disease. Early experience suggests that such advances have not been achieved and there is concern about developing minimal access surgical techniques in the face of potentially curable cancer. This article reviews the current state of knowledge based on published series; however, the current lack of controlled data in patients with extended follow-up makes this area highly controversial. Suggestions regarding the future of laparoscopic surgery are made and include the establishment of a national register and the development of controlled randomized trials.

Colon↗
PubMed1995

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↗
PubMed1995

Inflammatory markers following laparoscopic and open hernia repair.

Laparoscopic surgery may reduce the inflammatory response to surgery by the avoidance of a skin incision which is frequently the site of maximum tissue trauma. We hypothesized that the inflammatory response is less with minimally invasive procedures. The aim of this study was to evaluate the response of inflammatory mediators following laparoscopic and open hernia repair. Thirty-four patients undergoing unilateral primary inguinal hernia repair were prospectively assigned to either laparoscopic mesh hernia repair (n = 14), open mesh hernia repair (n = 11), or a Bassini repair (n = 9). Serum samples withdrawn prior to surgery, 6 h after surgery, and then again at 24 h after surgery were assayed for interleukin-6 and C-reactive protein content. Interleukin-6 levels at 24 h in the laparoscopic (13.1 +/- 3.1 pg/ml), open mesh (15.5 +/- 2.5 pg/ml), or Bassini group) (15.4 +/- 2.0 pg/ml) did not differ significantly. Neither did C-reactive protein levels at 24 h in the laparoscopic (12.4 +/- 2.7 pg/ml), open mesh (23.0 +/- 7.8 pg/ml), or Bassini group 18.6 +/- 6.6 pg/ml) differ significantly. The response of inflammatory mediators to hernia repair is not modified by undertaking the procedure laparoscopically.

C-Reactive Protein↗
PubMed1995

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↗
PubMed1995

Inflammatory breast carcinoma.

Inflammatory breast cancer (IBC) is a rare subtype of breast cancer traditionally associated with an extremely poor prognosis. The appearance of the effected breast can be misleading, with the incorrect diagnosis of an infective process, rather than a malignant disease, further delaying treatment. Compared with the results achieved by monotherapy with either surgery, radiotherapy or chemotherapy; multimodality treatments have achieved significant improvements in both disease-free and overall survival. The purpose of this article is to provide a comprehensive review of the current literature and highlight those areas where potential advances in the overall management of IBC have been made.

Adenocarcinoma↗
PubMed1995

Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells.

Differentiated cultures of Caco-2 human colonic cells were used to examine the importance of reduction of nonheme ferric iron, Fe(III), for transport across the brush border surface. Cultures accumulated approximately 100 pmol Fe/(h.mg protein) when 10 mumol Fe(III) as the nitrilotriacetic acid complex (1Fe:2NTA) was added to the apical compartment. Ascorbic acid enhanced cellular acquisition of iron in a dose-dependent manner, with a concentration as low as 8 mumol/L ascorbate increasing iron uptake by 50%. Similarly, the rate of iron transport from the apical to the basolateral compartment increased 5.6- and 30-fold when 100 and 1000 mumol/L ascorbic acid, respectively, were present in the apical chamber. Ascorbate-mediated stimulation of iron uptake was temperature dependent and required the reduction of Fe(III) to Fe(II), because it was inhibited by ascorbate oxidase and chelators of Fe(II). Moreover, Caco-2 cells recycled dehydroascorbic acid to ascorbic acid. Ferricyanide and Fe(II) chelators also partially inhibited iron uptake from a medium devoid of ascorbic acid. Intact Caco-2 cells exhibited a ferrireductase activity on the apical surface that accounted for the majority of iron accumulated by cells incubated in the absence of exogenous reductant. These data suggest that reduction of Fe(III) within the lumen or at the cell surface is required for transfer of this essential micronutrient across the intestinal brush border surface.

Ascorbic Acid↗
PubMed1995

Ascorbate offsets the inhibitory effect of inositol phosphates on iron uptake and transport by Caco-2 cells.

Differentiated monolayer cultures of Caco-2 human intestinal cells were used as a model to examine interactions between various dietary factors related to the intestinal uptake and absorption of nonheme Fe. Caco-2 cells accumulated 91-98 pmol Fe/mg protein from uptake buffer containing 12 nmol of Fe(III)-nitrilotriacetate during a 1-hr incubation at 37 degrees C. Addition of a 10-fold molar excess of inositol hexaphosphate (IP6) and its lesser phosphorylated derivatives (IP3, IP4, and IP5) decreased cellular uptake and transport of Fe from the lumenal compartment. Addition of ascorbic acid (AA) to the solution containing IPs stimulated Fe uptake and transport in a manner dependent upon the ratio of AA to IP and inversely proportional to the degree of phosphorylation of inositol (i.e., IP3 > IP4 > IP5 > IP6). A mixture of essential amino acids had minimal impact on Fe uptake in either the absence or presence of IPs. Cellular acquisition of Fe from solutions containing IPs was further enhanced by simultaneous addition of essential amino acids and AA. The stimulatory influence of ascorbic acid on Fe uptake from solutions containing IP6 was associated with an increase in the level of ferrous ion. These data further support the usefulness of Caco-2 cells as a model for investigating the effects of various dietary factors on mineral bioavailability.

Ascorbic Acid↗
PubMed1995

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↗
PubMed1994

Randomized controlled trial comparing Nissen fundoplication and the Angelchik prosthesis.

Sixty-one patients with gastro-oesophageal reflux refractory to medical therapy were entered into a prospective randomized trial comparing the Rossetti-Hell modification of the Nissen fundoplication (n = 31) with the Angelchik prosthesis (n = 30). Mean age, sex ratio, duration of symptoms, preoperative pH profiles and manometric findings were similar in the two groups. At a mean of 84 (range 64-105) months after closure of the trial 47 patients were available for review, eight had died from unrelated causes and six were lost to follow-up. Of the patients reviewed, 28 consented to endoscopy, 25 to oesophageal 24-h pH assessment and 20 to oesophageal manometry. Both fundoplication and the Angelchik prosthesis provided lasting control of gastro-oesophageal reflux, with 20 and 17 patients respectively maintaining a satisfactory outcome. There were no significant differences in pH profile between the groups but the Angelchik prosthesis had to be removed from three patients.

Esophagogastric Junction↗
PubMed1994

Inositol phosphates inhibit uptake and transport of iron and zinc by a human intestinal cell line.

To examine the influence of inositol phosphates on the uptake and absorption of Fe and Zn, Caco-2 cells were grown on either plastic (uptake studies) or porous membranes in bicameral chambers (transport/absorption studies). Caco-2, a human colon adenocarcinoma cell line, was selected as the test cell because it spontaneously differentiates into polarized enterocyte-like cells at confluency. Uptake of Fe (added as Fe-nitrilotriacetate complex) from a calcium-free solution by fully differentiated cells was 37 pmol/cm2. Addition of 10-fold molar excess of individual inositol phosphates (IP3, IP4, IP5 or IP6) decreased Fe solubility by 13 to 25% and reduced Fe uptake by 50 to 65%. The rate of transport of Fe from the apical solution into the basolateral chamber [1.4 +/- 0.1 pmol/(h.cm2)] decreased (34-96%) in proportion to the degree of phosphorylation of the inositol derivative in the apical compartment. Uptake and transepithelial transport of Zn were 246 +/- 5 pmol/cm2 and 23 +/- 1 pmol/(h.cm2), respectively. The solubility, uptake and rate of transport of Zn also decreased in proportion to the degree of phosphorylation of inositol. These results demonstrate the inhibitory influence of IP3-IP6 on the uptake and transport of Fe and Zn and support the usefulness of the Caco-2 human cell line as an appropriate model for evaluating the effects of specific dietary factors on trace metal bioavailability.

Colonic Neoplasms↗
PubMed1994

Endometriosis and umbilical swelling.

Umbilical endometriosis should be considered in the differential diagnosis of an umbilical swelling. The diagnosis is made by histological examination as clinically there may be no relationship between the swelling and menstruation.

Adult↗
PubMed1994

Laparoscopic cholecystectomy: safe and feasible in emphysematous cholecystitis.

We report three cases of emphysematous cholecystitis managed by laparoscopic cholecystectomy. The diagnosis was made by ultrasound in all cases. Two patients developed postoperative infections. There were no fatalities. The mean postoperative stay was 6 days. In experienced hands, laparoscopic removal of the gallbladder in emphysematous cholecystitis is feasible with good results.

Aged↗
PubMed1994

Methods of controlling presacral bleeding.

Rectal mobilization during abdominoperineal or low anterior resection involves careful dissection between the rectum and the sacrum. Inadvertent manipulation outside the avascular presacral space may damage presacral veins, causing troublesome and potentially life-threatening bleeding. We reviewed the current management of presacral bleeding, including the use of an endoscopic stapling device to control presacral bleeding.

Hemorrhage↗