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Biomedical subjects

M J Edwards

Publications and source records attributed to M J Edwards.

At least 73 records · Page 4Linked to original sources
PubMed2000

Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group.

INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.

Biopsy↗
PubMed2000

Preoperative lymphoscintigraphy for breast cancer does not improve the ability to identify axillary sentinel lymph nodes.

OBJECTIVE: To evaluate the role of preoperative lymphoscintigraphy in sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: Numerous studies have demonstrated that SLN biopsy can be used to stage axillary lymph nodes for breast cancer. SLN biopsy is performed using injection of radioactive colloid, blue dye, or both. When radioactive colloid is used, a preoperative lymphoscintigram (nuclear medicine scan) is often obtained to ease SLN identification. Whether a preoperative lymphoscintigram adds diagnostic accuracy to offset the additional time and cost required is not clear. METHODS: After informed consent was obtained, 805 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study, a multiinstitutional study involving 99 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Preoperative lymphoscintigraphy was performed at the discretion of the individual surgeon. Biopsy of nonaxillary SLNs was not required in the protocol. Chi-square analysis and analysis of variance were used for statistical comparison. RESULTS: Radioactive colloid injection was performed in 588 patients. In 560, peritumoral injection of isosulfan blue dye was also performed. A preoperative lymphoscintigram was obtained in 348 of the 588 patients (59%). The SLN was identified in 221 of 240 patients (92.1%) who did not undergo a preoperative lymphoscintigram, with a false-negative rate of 1.6%. In the 348 patients who underwent a preoperative lymphoscintigram, the SLN was identified in 310 (89.1%), with a false-negative rate of 8.7%. A mean of 2.2 and 2. 0 SLNs per patient were removed in the groups without and with a preoperative lymphoscintigram, respectively. There was no statistically significant difference in the SLN identification rate, false-negative rate, or number of SLNs removed when a preoperative lymphoscintigram was obtained. CONCLUSIONS: Preoperative lymphoscintigraphy does not improve the ability to identify axillary SLN during surgery, nor does it decrease the false-negative rate. Routine preoperative lymphoscintigraphy is not necessary for the identification of axillary SLNs in breast cancer.

Axilla↗
PubMed2000

Comparisons among the Holden Psychological Screening Inventory (HPSI), the Brief Symptom Inventory (BSI), and the Balanced Inventory of Desirable Responding (BIDR).

Issues of reliability, item latent structure, and faking on the Holden Psychological Screening Inventory (HPSI), the Brief Symptom Inventory (BSI), and the Balanced Inventory of Desirable Responding (BIDR) were examined with a sample of 300 university undergraduates. Reliability analyses indicated that scales from all inventories had acceptable internal consistency. Confirmatory item principal component analyses supported the structures and scoring keys of the HPSI and the BIDR, but not the BSI. Although all inventories were susceptible to faking, validity indices of the HPSI and the BIDR could correctly classify over two-thirds of test respondents as either responding honestly or as faking.

Adult↗
PubMed2000

Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used.

PURPOSE: Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN. Some investigators advocate SLN biopsy using injection of a vital blue dye, others recommend radioactive colloid, and still others recommend the use of both agents together. PATIENTS AND METHODS: A total of 806 patients were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye alone or radioactive colloid alone) or dual-agent injection at the discretion of the operating surgeon. All patients underwent attempted SLN biopsy followed by completion level I/II axillary lymph node dissection to determine the false-negative rate. RESULTS: There was no significant difference (86% v 90%) in the SLN identification rate among patients who underwent single- versus dual-agent injection. The false-negative rates were 11.8% and 5.8% for single- versus dual-agent injection, respectively (P <.05). Dual-agent injection resulted in a greater mean number of SLNs identified per patient (2. 1 v 1.5; P <.0001). The SLN identification rate was significantly less for patients older than 50 years as compared with that of younger patients (87.6% v 92.6%; P =.03). Upper-outer quadrant tumor location was associated with an increased likelihood of a false-negative result compared with all other locations (11.2% v 3. 9%; P <.05). CONCLUSION: In multi-institutional practice, SLN biopsy using dual-agent injection provides optimal sensitivity for detection of nodal metastases. The acceptable SLN identification and false-negative rates associated with the dual-agent injection technique indicate that this procedure is a suitable alternative to routine axillary dissection across a wide spectrum of surgical practice and hospital environments.

Axilla↗
PubMed2000

The role of the ultrasonically activated shears and vascular cutting stapler in hepatic resection.

Hemorrhage and liver failure are the two greatest concerns for patients undergoing major liver resection. Inflow occlusion (Pringle maneuver) is often used to minimize blood loss, but hepatic ischemia results in an increased risk of postoperative hepatic dysfunction. We report our experience with the Harmonic Scalpel ultrasonically activated shears (UAS; Ethicon Endo-Surgery, Cincinnati, OH) and a vascular stapler for hepatic resection as technological advances that aid in minimizing blood loss and thereby reduce the need for inflow occlusion. We retrospectively reviewed liver resections performed from September 1997 through July 1998, in which the UAS and articulating vascular endoscopic linear cutting stapler were used. The vascular stapler was used to divide the appropriate portal vein branch and hepatic vein(s) before parenchymal transection. Parenchymal dissection was performed with UAS to a depth of approximately 2 to 3 cm, and the remainder of the liver parenchyma was divided by a clamp crush and clip and suture ligate technique. Patients underwent segmental resection (n = 12), lobectomy (n = 13), or extended lobectomy (n = 11). Resection was performed for metastatic disease, primary liver tumors, or benign disease in 21, 8, and 7 patients, respectively. A Pringle maneuver was performed in 7 of 36 patients (mean clamp time, 8 minutes). The median required intraoperative blood transfusion was 0 units of packed red blood cells. Major and minor complications occurred in 12 and 3 patients, respectively. Two deaths were related to pneumonia and abdominal infection. The vascular stapler safely and securely divides portal vein branches and hepatic veins. The UAS initiates parenchymal transection with minimal blood loss. These two technologies facilitate the surgeon's aim of liver resection without blood transfusion or Pringle maneuver.

Blood Loss, Surgical↗
PubMed1999

The cost, effectiveness and cost effectiveness of removal and retention of asymptomatic, disease free third molars.

PURPOSE OF INVESTIGATION: The study was undertaken to identify the least costly, most effective and most cost-effective management strategy for asymptomatic, disease free mandibular third molars. METHODS AND PATIENTS: A decision tree model of the outcomes of mandibular third molar retention and removal was constructed. Probability data for possible outcomes were obtained from a comprehensive literature review and entered into the decision tree. The cost to the NHS in treating each outcome was calculated. 100 patients attending the oral surgery clinics, University of Wales Dental Hospital rated the effect of each outcome on their own life. The cost and effectiveness data for each outcome were entered into the decision tree and the analyses were conducted by 'folding back' the decision tree based on the probabilities. MAIN FINDINGS: Mandibular third molar retention was less costly (170 Pounds), more effective (69.5 effectiveness units on a 100 point scale) and more cost-effective (2.43 Pounds per unit of effectiveness) than removal (226 Pounds, 63.3 and 3.57 Pounds respectively). These findings were sensitive to changes in the probability of pericoronitis, periodontal disease and caries. PRINCIPAL CONCLUSIONS: Mandibular third molar retention is less costly to the NHS, more effective for the patient and more cost-effective to both parties than removal. However, should the likelihood of developing pericoronitis, periodontal disease and caries increase substantially then removal becomes the more cost-effective strategy.

Cost-Benefit Analysis↗
PubMed1999

Interleukin-10 suppresses hepatic ischemia/reperfusion injury in mice: implications of a central role for nuclear factor kappaB.

Ischemia/reperfusion injury of the liver requires the participation of proinflammatory cytokines, chemokines, and adhesion molecules, many of which are regulated by the transcription factor nuclear factor kappaB (NFkappaB). The anti-inflammatory cytokine, interleukin-10 (IL-10) affects inflammatory reactions, at least in part, through inhibitory effects on the transcription factor, NFkappaB. The objective of the current study was to determine whether IL-10 could suppress hepatic ischemia/reperfusion-induced NFkappaB activation and the ensuing inflammatory liver injury. C57BL/6 mice underwent partial hepatic ischemia and reperfusion with or without intravenous injections of recombinant murine IL-10. Hepatic NFkappaB activation was induced in a time-dependent fashion. IL-10 suppressed NFkappaB activation as well as messenger RNA expression of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2). In addition, IL-10 reduced serum levels of TNF-alpha and MIP-2. Hepatic neutrophil recruitment, liver edema, and hepatocellular injury were all significantly reduced by IL-10. The data suggest that IL-10 protects against hepatic ischemia/reperfusion injury by suppressing NFkappaB activation and subsequent expression of proinflammatory mediators.

Animals↗
PubMed1999

Requirement for interleukin-12 in the pathogenesis of warm hepatic ischemia/reperfusion injury in mice.

Hepatic ischemia and reperfusion causes neutrophil-dependent liver injury. Although the mechanisms of ischemia/reperfusion-induced liver neutrophil recruitment are somewhat understood, less is known regarding the early events that initiate the inflammatory injury. Using a murine model of partial hepatic ischemia and reperfusion, we evaluated the role of endogenous interleukin (IL)-12 in this inflammatory response. Hepatic ischemia for 90 minutes and reperfusion for up to 4 hours resulted in hepatocyte expression of IL-12. By 8 hours of reperfusion there were large increases in serum levels of interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha). In addition, hepatic ischemia/reperfusion caused significant increases in liver neutrophil recruitment, hepatocellular injury, and liver edema, as defined by liver myeloperoxidase content, serum alanine aminotransferase, and liver wet to dry weight ratios, respectively. In mice treated with neutralizing antibody to IL-12 and in mice deficient in the IL-12 p40 gene, ischemia/reperfusion-induced increases in IFNgamma and TNFalpha were greatly diminished. These conditions also caused significant reductions in liver myeloperoxidase content and attenuated the parameters of liver injury. The data suggest that IL-12 is required for the full induction of injury after hepatic ischemia and reperfusion.

Alanine Transaminase↗
PubMed1999

Enhanced pulmonary expression of CXC chemokines during hepatic ischemia/reperfusion-induced lung injury in mice.

BACKGROUND: Hepatic ischemia/reperfusion injury during both hepatic resection and transplantation may lead to local and systemic organ dysfunction. Proinflammatory mediators released by Kupffer cells during the initial phase of ischemia/reperfusion are thought to be involved in the development of neutrophil-mediated lung injury. However, the precise factors involved in lung recruitment of neutrophils are unclear. The objective of current study was to determine whether the CXC chemokines, macrophage inflammatory protein-2 (MIP-2) and KC, contribute to pulmonary neutrophil recruitment and injury following hepatic ischemia/reperfusion. METHODS: C57BL/6 mice were subjected to 90 min of partial hepatic ischemia and 3, 6, and 9 h of reperfusion. Neutrophil accumulation in lung was assessed by lung content of myeloperoxidase (MPO). MIP-2 and KC mRNA were measured using RT-PCR. Lung edema was quantified by wet to dry weight ratios. RESULTS: Three hours after hepatic reperfusion, serum levels of tumor necrosis factor-alpha were increased. Lung expression of both MIP-2 and KC mRNA was also increased at this time. Both MIP-2 and KC mRNA expression remained elevated 9 h after reperfusion, although levels of MIP-2 mRNA were significantly lower than at 3 h. Pulmonary recruitment of neutrophils was increased within 3 h after reperfusion, but returned to baseline levels by 9 h. Lung edema was increased 3 and 9 h after reperfusion. Neutralization of MIP-2 or KC with antibody significantly decreased lung edema 9 h after reperfusion. CONCLUSIONS: These data suggest that mediators released during hepatic ischemia/reperfusion induce the expression of MIP-2 and KC in the lung. In addition, it appears that MIP-2 and KC contribute to lung neutrophil accumulation and the associated pulmonary injury following hepatic ischemia/reperfusion.

Animals↗
PubMed1999

Mechanisms of leukocyte-mediated tissue injury induced by interleukin-2.

In this review we discuss the effects of interleukin-2 (IL-2) therapy on trafficking of leukocytes and platelets to normal organs. The use of animal models has allowed the elucidation of events leading to damage and/or dysfunction of normal tissues after IL-2 administration. These studies have shown that acute toxicity induced by IL-2 is mediated primarily by neutrophils. Chronic toxicity results from the adhesion and transmigration of activated lymphocytes into normal organs. Platelet-derived microvascular thrombosis also contributes to the vascular toxicity of IL-2. A better understanding of these mechanisms may lead to the development of interventions that will significantly improve the therapeutic efficacy of IL-2.

Animals↗
PubMed1999

IL-13 activates STAT6 and inhibits liver injury induced by ischemia/reperfusion.

Hepatic ischemia/reperfusion injury is initiated by the activation of Kupffer cells and their subsequent release of proinflammatory mediators, including tumor necrosis factor-alpha (TNFalpha). These mediators stimulate a cascade of events including up-regulation of CXC chemokines and vascular endothelial adhesion molecules, leading to hepatic neutrophil recruitment and tissue injury. Interleukin-13 (IL-13) is a cytokine that has been shown to suppress macrophage production of proinflammatory mediators. The objective of the current study was to determine whether IL-13 could regulate the liver inflammatory injury induced by ischemia and reperfusion. C57BL/6 mice underwent 90 minutes of partial hepatic ischemia followed by reperfusion with or without intravenous administration of recombinant murine IL-13. Hepatic ischemia/reperfusion increased expression of TNFalpha and macrophage inflammatory protein-2 (MIP-2), leading to hepatic neutrophil recruitment, hepatocellular injury, and liver edema. Administration of IL-13 reduced the production of TNFalpha and MIP-2 mRNA and protein. IL-13 suppressed liver neutrophil recruitment by up to 72% and hepatocellular injury and liver edema were each reduced by >60%. Administration of IL-13 had no effect on liver NFkappaB activation, but greatly increased the activation of STAT6. The data suggest that the hepatoprotective effects of IL-13 may be a result of STAT6 activation.

Animals↗
PubMed1999

Secretory leukocyte protease inhibitor in mice regulates local and remote organ inflammatory injury induced by hepatic ischemia/reperfusion.

BACKGROUND & AIMS: This study identified and characterized the hepatic expression of secretory leukocyte protease inhibitor (SLPI) during hepatic ischemia and reperfusion in mice. In addition, the effects of exogenously administered and endogenous SLPI on liver and lung injury induced by hepatic ischemia and reperfusion were evaluated. METHODS: C57BL/6 mice underwent 90 minutes of partial hepatic ischemia and 4 hours of reperfusion in the presence or absence of exogenous SLPI or neutralizing antibodies to SLPI. RESULTS: Intravenous infusion of SLPI reduced liver and lung damage and diminished neutrophil accumulation in both organs. These effects were accompanied by reduced serum levels of tumor necrosis factor (TNF)-alpha and the CXC chemokine macrophage inflammatory protein (MIP)-2. SLPI also suppressed activation of the transcription factor NF-kappaB in liver. Hepatic ischemia and reperfusion caused increased expression of SLPI messenger RNA and SLPI protein, which was found in hepatocytes. Treatment of mice with anti-SLPI enhanced serum levels of TNF-alpha and MIP-2 and increased hepatic neutrophil accumulation and amount of liver injury. CONCLUSIONS: These data indicate that SLPI has protective effects against hepatic ischemia/reperfusion injury and suggest that endogenous SLPI functions to regulate the hepatic inflammatory response.

Animals↗
PubMed1999

An embryological perspective on congenital portacaval shunt: a rare anomaly in a patient with hepatocellular carcinoma.

We describe a 42-yr-old woman with hepatocellular carcinoma and a congenital portacaval shunt. A computed tomography (CT) scan of the abdomen showed a prominent left hepatic lobe extending into the lower abdomen. A large encapsulated, necrotic-appearing mass was seen within the right hepatic lobe. The patient underwent hepatic resection, during which the continuation of the confluence of the splenic and superior mesenteric veins was found to empty directly into the inferior vena cava, bypassing the hepatic parenchyma. An extended right hepatic lobectomy was performed with a complete excision of the mass (T3 N0 M0, stage III). The patient had an uneventful postoperative course. To our knowledge, this is the first reported case of this anomaly in a living adult having undergone hepatectomy.

Adult↗
PubMed1999

Hsp72 antigen expression in the proliferative compartment of involved psoriatic epidermis.

Oxidative damage to growth regulatory proteins has been implicated in the aetiology of psoriasis. However, the transient synthesis of heat shock proteins has been shown to protect cells against the adverse effects of oxidative and other forms of physiological stress. This study has used an hsp72 monoclonal antibody to measure inducible 72 kDa heat shock protein expression in heat stressed normal human skin and established plaque psoriasis. Hsp72 was detected in the basal and suprabasal layer cells of heat-stressed normal skin, and in 12 involved psoriasis lesions. Hsp72 expression was not detected in unstressed normal skin or in 12 cases of uninvolved psoriasis. Immunoprecipitation and Western blotting of cell lysates from heat stressed normal skin and involved psoriasis lesions confirmed the presence of a 72 kDa polypeptide with hsp72 immunoreactivity. The MIB-1 monoclonal antibody was used to determine the proliferative fraction of normal and involved psoriastic epidermis. The Ki67 antigen was localised to the nuclei of basal and suprabasal layer cells of normal and involved psoriatic epidermis. Involved psoriatic epidermis contained a higher number of proliferating keratinocytes when compared with normal skin. The study has also demonstrated a strong correlation between hsp72 expression and keratinocyte proliferation in involved psoriatic epidermis (r=0.864, p<0.001). We believe that the 72 kDa inducible heat shock protein performs a protective function in the proliferative compartment of normal and involved psoriatic skin.

Antibodies, Monoclonal↗
PubMed1999

Interleukin-10 inhibits pulmonary NF-kappaB activation and lung injury induced by hepatic ischemia-reperfusion.

Hepatic ischemia and reperfusion cause local and remote organ injury. This injury culminates from an integrated cascade of proinflammatory cytokines, chemokines, and adhesion molecules, many of which are regulated by the transcription factor nuclear factor-kappaB (NF-kappaB). The anti-inflammatory cytokine interleukin-10 (IL-10) has been shown to have inhibitory effects on NF-kappaB. The objective of the current study was to determine whether IL-10 could suppress pulmonary NF-kappaB activation and ensuing lung injury induced by hepatic ischemia-reperfusion. C57BL/6 mice underwent partial hepatic ischemia with or without intravenous administration of IL-10. Hepatic ischemia-reperfusion resulted in pulmonary NF-kappaB activation, increased mRNA expression of tumor necrosis factor-alpha (TNF-alpha), and macrophage inflammatory protein-2 (MIP-2), as well as increased pulmonary neutrophil accumulation and lung edema. Administration of IL-10 suppressed lung NF-kappaB activation, reduced TNF-alpha and MIP-2 mRNA expression, and decreased pulmonary neutrophil recruitment and lung injury. The data suggest that IL-10 protects against hepatic ischemia and reperfusion-induced lung injury by inhibiting lung NF-kappaB activation and the resulting pulmonary production of proinflammatory mediators.

Animals↗