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Biomedical subjects

J F Sweeney

Publications and source records attributed to J F Sweeney.

At least 19 recordsLinked to original sources
PubMed2006

Gastrotomy with anvil "dunk": a novel technique for gastrojejunostomy in the patient undergoing laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Many techniques for performing the gastrojejunostomy required in the laparoscopic roux-en-Y gastric bypass (LRYGB) have been described. The current study presents the results of a previously unreported method. METHODS: A total of 21 patients (2 men and 19 women) with morbid obesity underwent LRYGB over a period of 5 months. The gastrojejunostomy was created by performing a gastric transection to form a 20- to 30-ml pouch using a linear stapler. This was followed by gastrotomy using an ultrasonic scalpel along the anterior surface of the pouch. A purse-string suture then was placed circumferentially using standard laparoscopic intracorporeal suturing with an Endo-stitch device. Finally, a 25-mm circular stapler anvil was placed within the abdomen via the 15-mm left lower quadrant port site. The shaft of the anvil was grasped; the head of the anvil was "dunked" into the gastrotomy; and the purse-string suture was tied intracorporeally. RESULTS: A total of 21 patients have undergone LRYGB at the authors' institution using this technique. The early results have been excellent in all cases, with no leaks, no strictures, and no obstructions. CONCLUSION: Gastrotomy with anvil dunk is a reproducible and safe method for constructing the gastrojejunostomy. It is an advanced laparoscopic technique that closely resembles open surgical techniques and provides a safe alternative to existing methods.

Adult↗
PubMed2005

Historical research: examining documentary sources.

In this paper John Sweeney outlines key principles for conducting a study employing an historical design based on documentary analysis. It derives in part from his PhD study, in which he employs an historical design based on documentary analysis to investigate the delay in introduction of intellectual disability nursing into the Republic of Ireland from 1921 until 1958. This study examines the social, political and professional context to the decision to forgo the recognition of a professional nursing qualification and education process in intellectual disability until 1958.

Documentation↗
PubMed2003

Laparoscopic approach to the management of intraabdominal unicentric Castleman's disease.

Castleman's disease, or angiofollicular lymphoid hyperplasia, is a rare lymphoproliferative disorder of unknown etiology. We present the case of an 18-year-old woman who was admitted with symptoms of fatigue, weakness, early satiety, and weight gain. A subhepatic mass anterior to the pancreas was discovered on ultrasound. After being treated via the laparoscopic approach with complete surgical resection she recovered well. This case thus represents a new application for laparoscopy and expands the indications for its use.

Abdomen↗
PubMed2002

Laparoscopic ventral hernia repair during the learning curve.

Large series of laparoscopic ventral hernia repair have shown excellent results. However, published comparative studies have had conflicting outcomes. We retrospectively reviewed the first 29 laparoscopic ventral hernia repairs performed at a VA Medical Center from January 2000 to June 2001. The outcome was compared to that of open repairs performed during the same time period. Outcomes between the groups were similar in all respects, except for the length of stay. The conversion rate for the laparoscopic approach was 13.8%. There was one death in the laparoscopic group due to an unrecognized enterotomy. There were three recurrences in the open group and one in the laparoscopic group with a mean follow up of 13 months. In our series, laparoscopic hernia repair resulted in a shorter hospital stay but no other significant benefits, along with a risk of missed enterotomy. The risk-benefit ratio for this procedure may be high during the learning curve.

Clinical Competence↗
PubMed2001

Caspase-3 inhibition partially protects oxidant production in apoptotic human neutrophils.

UNLABELLED: Apoptotic PMN lose functional activity, which emphasizes the tissue injury limiting potential of PMN apoptosis. Caspase-3 activation is the first step in the execution phase of apoptosis. We hypothesized that PMN functional activity, as evidenced by oxidant production, can be restored in apoptotic PMN by inhibition of caspase-3. METHODS: To accelerate PMN apoptosis, PMN were UV-irradiated for 15 min as previously described. PMN were pretreated with the caspase-3 inhibitor DEVD-fmk (100 microM) for 30 min prior to UV. PMN apoptosis was quantitated by flow cytometry with CD16 staining. Oxidant production in response to 10 microM PMA was quantitated fluorometrically using the method of Hyslop and Sklar. Caspase-3 activity was quantitated fluorometrically using a commercially available assay. RESULTS: UV-treated PMN demonstrated a 3-fold increase in caspase-3 activity. This was associated with a significant increase in apoptotic PMN and a 10-fold decrease in oxidant production compared to control PMN. DEVD-fmk blocked increases in caspase-3 activity and significantly reduced PMN apoptosis. Oxidant production was increased 5-fold compared to UV-treated PMN but was still significantly less than control PMN. CONCLUSIONS: In UV-accelerated PMN apoptosis, inhibition of caspase-3 activity partially protects oxidant production in apoptotic PMN. This suggests that signaling events in the initiation phase of PMN apoptosis, which are proximal to caspase-3 activation, may in part be responsible for loss of oxidant production in apoptotic PMN independent of caspase-3 activity.

Apoptosis↗
PubMed2001

Inhibition of mono-ADP-ribosyltransferase activity during the execution phase of apoptosis prevents apoptotic body formation.

The objective of this study was to understand factors responsible for apoptotic body formation and release during apoptosis. We have found that inhibition of mono-ADP ribosylation after ultraviolet (UV) light induction of apoptosis in HL-60 cells does not block caspase-3 activation, gelsolin cleavage, or endonucleolytic DNA fragmentation. However, the cytoskeletal features of apoptosis leading to apoptotic body formation and release were inhibited by meta-iodobenzylguanidine (MIBG) and novobiocin, potent inhibitors of arginine-specific mono-ADP-ribosyltransferases (mono-ADPRTs). Suppression of mono-ADP ribosylation as late as 120 min following UV irradiation blocked the depolymerization of actin and release of apoptotic bodies. This suggested that the cytoskeletal changes of apoptosis may be decoupled from the caspase cascade and that there may be a biochemical event either distal to or independent of caspase-3 that regulates apoptotic body formation. To test the hypothesis that ADP ribosylation of actin may occur with the induction of apoptosis, an in vivo assay of mono-ADPRT activity using an antibody against ADP-ribosylarginine was used. An approximately 64% increase in the ADP ribosylation of actin was observed at 2 h following exposure to UV light. When MIBG or novobiocin was present, the ADP ribosylation of actin was only 14-18% above the levels observed in control nonirradiated cells. The current study is the first to demonstrate a relationship between ADP-ribosylation of actin and the formation of apoptotic bodies.

3-Iodobenzylguanidine↗
PubMed2001

Nuclear dependence of sulfur mustard-mediated cell death.

Although sulfur mustard (SM) has been reported to be a DNA alkylating agent, it is not clear how much of the cytotoxicity of this agent is secondary to DNA damage. To test the hypothesis that the presence of a nucleus is required for the toxicity of sulfur mustard, enucleated endothelial cytoplasts were treated with SM. Using a combination of biochemical and microscopic assays, we demonstrate that some aspects of SM-induced cell death may be dependent on the presence of a nucleus, while others may not be. For example, it was found that cytoskeletal changes, such as loss of stress fibers and rounding, proceed in response to sulfur mustard treatment even in the absence of a nucleus. However, significant further increases in caspase activity and the associated phosphatidylserine translocation were not observed in cytoplasts treated with 500 microM SM for 6 h (following a 20-h recovery at the end of cytoplast preparation). In contrast, cytoplasts treated with chelerythrine, an agent previously reported to induce rapid apoptosis, demonstrated increases in caspase activity in cytoplasts comparable to that observed in the nucleated cells. This indicates that sulfur mustard-induced alkylation of nuclear DNA may be an important stimulus for activation of caspases in nucleated cells. Interestingly, the baseline caspase activity in cytoplasts was greater than in nucleated cells. Analysis of the time course of caspase activation in untreated adherent cytoplasts indicated that the activity increases initially and then stabilizes by 8 h to a low level that was comparable to the level observed at 26 h in untreated cytoplasts. This indicates that cytoplasts are able to tolerate stable low levels of caspase activity and not proceed immediately into the execution phase of apoptosis. The cytoplast model may be quite useful in the toxicological assessment of agents that are thought to exert their toxicity through DNA damage.

Animals↗
PubMed2000

Efficacy of the laparoscopic approach for anterior lumbar spinal fusion.

BACKGROUND: This study compares the immediate postoperative outcomes in patients who undergo laparoscopic and open anterior lumbar spinal fusion and describes the learning curve associated with the performance of this procedure. METHODS: The charts of patients who underwent anterior lumbar spinal fusion between January 1995 and July 1999 were reviewed. Data pertaining to the operation and postoperative course were analyzed and compared. RESULTS: Eighty-nine patients underwent anterior lumbar spinal fusion. Fourteen patients were excluded; a full analysis was performed on the records of the remaining 75 patients. Fifty-five patients underwent an attempted laparoscopic procedure, and 20 patients underwent an open procedure. The conversion rate was 38% (21/55 patients) in the group who underwent the laparoscopic procedure. In the 34 patients whose laparoscopic procedure was completed, there was significantly less blood loss and shorter postoperative ileus, but the operative time was longer, when compared with patients who underwent the open procedure. The laparoscopic procedures performed in 1999 resulted in fewer conversions, less blood loss, and a shorter operating room time, when compared with the laparoscopic procedures in 1998. CONCLUSIONS: Laparoscopic anterior lumbar spinal fusion improves immediate postoperative results when compared with open anterior lumbar spinal fusion.

Adult↗
PubMed2000

Chelerythrine chloride induces rapid polymorphonuclear leukocyte apoptosis through activation of caspase-3.

Polymorphonuclear leukocytes (PMN) play a primary role in the initiation and propagation of inflammatory responses. PMN apoptosis is a major mechanism associated with the resolution of inflammatory reactions. Understanding mechanisms associated with PMN apoptosis will be of critical value in the development of novel pharmacological treatment strategies for local and/or systemic inflammatory disorders. The present study demonstrates that chelerythrine chloride induces human PMN to undergo rapid and synchronous progression into the apoptotic process via a PKC-independent mechanism. The appearance of the morphological features of apoptosis in chelerythrine-treated PMN is preceded by a significant upregulation in caspase-3 activity. GM-CSF (a cytokine that protects PMN in several models of PMN apoptosis) does not protect PMN from chelerythrine chloride-induced apoptosis.

Alkaloids↗
PubMed1999

Granulocyte-macrophage colony-stimulating factor rescues human polymorphonuclear leukocytes from ultraviolet irradiation-accelerated apoptosis.

INTRODUCTION: Bacterial lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) delay PMN apoptosis during in vitro culture. The present study was undertaken to determine if LPS and GM-CSF can rescue UV-irradiated PMN from undergoing apoptosis and to determine the role of extracellular signal-regulated kinase (ERK) in this process. MATERIALS AND METHODS: PMN were preincubated with LPS (20 ng/ml) and GM-CSF (100 units/ml) for 60 min before being UV-irradiated for 15 min. Additional PMN were UV-irradiated for 15 min and then treated with LPS and GM-CSF. To determine the role of ERK in protection or rescue of PMN from apoptosis, PMN were preincubated with PD098059 for 30 min. Morphologic features of apoptosis were determined 4 h after UV irradiation. DNA laddering was confirmed by agarose gel electrophoresis. RESULTS: LPS and GM-CSF pretreatment significantly protected PMN from UV-accelerated apoptosis, although GM-CSF was more effective than LPS. Only GM-CSF rescued PMN that had already been exposed to UV irradiation from undergoing apoptosis. Time response experiments demonstrated that GM-CSF rescued a significant percentage of PMN when added up to 90 min after UV irradiation. Inhibition of ERK with PD098059 abrogated the protective effect of LPS and GM-CSF and blocked rescue of PMN from apoptosis by GM-CSF. CONCLUSIONS: LPS and GM-CSF protect PMN, whereas only GM-CSF can rescue PMN from UV-accelerated apoptosis. The ERK-signaling pathway plays an important role in the protection and/or rescue of PMN from UV-accelerated apoptosis, but appears to be a proximal event in this process. This study provides further insight into factors that regulate PMN apoptosis and provides a novel approach for investigating signal transduction pathways involved in PMN apoptosis.

Apoptosis↗
PubMed1999

Laparoscopic splenectomy in patients with hematologic malignancies.

BACKGROUND: Although laparoscopic splenectomy (LS) for benign hematologic disease is well accepted, its role in hematologic malignancies is not clearly defined. This study examined the efficacy and feasibility of LS for hematologic malignancies. METHODS: Records were reviewed from patients who underwent LS at two university hospitals. Charts from 77 open splenectomies for malignancy (OM) during the same period were also reviewed. RESULTS: Fifty-three patients underwent LS, 22 for hematologic malignancies (LM) and 31 for benign hematologic disorders (LB). Median splenic weight was greater in the LM group (930 g) than in the LB group (164 g, P = 0.001). LM was associated with longer operations and greater blood loss than was LB. LM had a 41% conversion rate. Morbidity, mortality, and transfusion rates were similar. Median hospital stay was shorter for LM (4 days) than for OM (6 days, P = 0.001). CONCLUSIONS: LS is feasible in hematologic malignancies but is associated with increased operative time and blood loss and a high conversion rate. Morbidity and mortality, however, was similar. Shorter hospital stays for LM compared with OM may translate into earlier recovery and initiation of antineoplastic therapy.

Adult↗
PubMed1998

Lipopolysaccharide protects polymorphonuclear leukocytes from apoptosis via tyrosine phosphorylation-dependent signal transduction pathways.

BACKGROUND: The present study was undertaken to determine if tyrosine phosphorylation signal transduction pathways, which are known to be activated in polymorphonuclear leukocytes (PMN) by lipopolysaccharide (LPS), play a role in priming of PMN oxidative burst and protection of PMN from apoptosis by LPS, and to determine if an interface between these two signaling pathways exists. METHODS: PMN were combined with or without 10-fold serial dilutions (0.1 ng-1 microgram/ml) of LPS and incubated at 37 degrees C/5% CO2. After 24 h PMN apoptosis was assessed using fluorescence microscopy and DNA agarose gel electrophoresis. Additional PMN were pretreated with the tyrosine kinase inhibitors genistein and herbamycin A before addition of LPS. Tyrosine phosphorylation was detected by immunoblotting. Oxidant production was quantitated by following the oxidation of a chromophore to its fluorescent product. RESULTS: LPS delayed the onset of apoptosis and prolonged the survival of PMN in a dose-dependent fashion. Both tyrosine kinase inhibitors blocked the protective effect of LPS on PMN apoptosis; however, only genistein blocked the priming effect of LPS on PMN oxidative burst. CONCLUSIONS: Tyrosine phosphorylation signal transduction pathways are central to protection of PMN from apoptosis by LPS. Although tyrosine phosphorylation pathways also play a role in priming of the oxidative burst in PMN, our data suggest that there is not an interface between these important signaling pathways.

Apoptosis↗
PubMed1998

Intact autocrine activation and cytokine production by PMNs from injured adults with elevated Candida antigen titres.

Injured patients with Candida antigen titres have increased mortality due to sepsis. Polymorphonuclear leucocytes (PMNs) from injured patients with elevated Candida antigen titres demonstrate impaired function against Candida albicans growth when compared with PMNs from injury matched controls. To determine if PMN dysfunction is global, PMNs from patients with positive Candida antigen titres were evaluated for their ability to activate the anticandidal function of normal PMNs (autocrine activation) and to produce tumour necrosis factor (TNF) and interleukin 8 (IL8), known activators of PMN anticandidal function, this study demonstrates that the PMN dysfunction is not global, as PMN cytokine production and autocrine activation remain intact.

Adult↗
PubMed1998

Autocrine/paracrine modulation of polymorphonuclear leukocyte survival after exposure to Candida albicans.

Polymorphonuclear leukocytes (PMN) play a central role in the host response to injury and infection. These terminally differentiated phagocytes have a limited life span, after which they undergo spontaneous apoptosis. PMN life span can be significantly prolonged by several naturally occurring cytokines, and PMN are now known to be capable of cytokine production in response to various antigenic stimuli. These facts suggest the possibility that PMN possess an autocrine/paracrine mechanism for the control of their own survival. The present study was undertaken to test this hypothesis. Supernatants from PMN that had been incubated with Candida albicans for 18 h significantly decreased the number of fresh PMN demonstrating features of apoptosis and increased the percentage of viable PMN during in vitro culture. This was demonstrated by monitoring morphologic features of apoptosis with fluorescence microscopy and DNA endonuclease activity with agarose gel electrophoresis. Significant levels of tumor necrosis factor (TNF) were detectable in the supernatants of PMN that had been stimulated with C. albicans, as determined using a TNF-sensitive cell line. Neutralization of TNF biologic activity with a specific monoclonal antibody partially abrogated the supernatant-mediated prolongation of PMN survival. The present study demonstrates that PMN possess a mechanism for the modulation of their own survival, which in part may be through the production of TNF.

Antibodies, Monoclonal↗
PubMed1997

Ultraviolet irradiation accelerates apoptosis in human polymorphonuclear leukocytes: protection by LPS and GM-CSF.

Polymorphonuclear leukocytes (PMN) play a central role in host response to injury and infection. Understanding factors that regulate PMN survival may therefore have a major influence on the development of novel treatment strategies for controlling life-threatening infections, as well as local and systemic inflammatory responses. Unfortunately, the presently utilized in vitro culture model of PMN apoptosis makes the examination of early biochemical events surrounding PMN apoptosis very difficult. This study demonstrates that a short course of UV irradiation (15 min) can be used to induce rapid progression of PMN through the apoptotic process with 70-90% of PMN displaying features of apoptosis by 4 h after UV exposure. Bacterial lipopolysaccharide and granulocyte-macrophage colony-stimulating factor, which are known to prolong PMN survival during in vitro culture, also protected PMN from UV-accelerated apoptosis. The UV-accelerated model of PMN apoptosis provides another valuable tool for the investigation of early signaling pathways associated with inducing or delaying PMN apoptosis.

Apoptosis↗
PubMed1997

Candida antigen titre dilution and death after injury.

BACKGROUND: Candida infections affect outcome after injury. Candida antigen titres were used to detect these infections early. This study was undertaken to correlate Candida antigen titre dilution with conventional injury scoring and outcome after severe injury. METHODS: Candida antigen titres were determined by agglutination when clinically apparent source(s) of Candida were noted, when Candida was grown in culture of body fluids, or when unexplained clinical deterioration occurred. The findings were compared with the Injury Severity Score (ISS). RESULTS: Seventy-five seriously injured adults (median ISS 25 (range 18-50)) developed raised Candida antigen titres. Multivariate analysis showed that age and Candida antigen titre correlated significantly with mortality, but not with each other. Culture evidence of Candida, or lack thereof, did not correlate with Candida antigen titre or mortality. Sixteen of 75 patients died, 14 from bacterial sepsis and none from Candida infection. CONCLUSION: In seriously injured adults, the mortality rate is related to raised Candida antigen titres. The association between Candida antigen titre and mortality, although real, remains unexplained.

Adult↗
PubMed1996

Identification of an amphotericin B resistant strain of Candida albicans using a rapid 3H-glucose incorporation microassay.

Using a 3H-glucose incorporation assay, antifungal sensitivity testing undertaken on an isolate of Candida albicans cultured from the blood of a bone marrow transplant patient documented resistance to amphotericin B but sensitivity to fluconazole and itraconazole. Information obtained from in vitro antifungal sensitivity testing can be used to direct in vivo antifungal therapy. Widespread application of standardized in vitro antifungal sensitivity testing is needed.

Adult↗