PubMed Health⌕ Search

Biomedical subjects

M R Kell

Publications and source records attributed to M R Kell.

At least 19 recordsLinked to original sources
PubMed2007

PET CT imaging in patients undergoing sentinel node biopsy for melanoma.

AIMS: Sentinel lymph node biopsy (SLNB) has been adopted in the surgical treatment of melanoma to reduce morbidity and enhance staging. Positron emission tomography with computerised tomography (PET/CT) has been utilised in the staging of patients with malignancy though the role of this imaging modality in early stage melanoma is unclear. This study examined the preoperative value of PET/CT in patients undergoing SLNB for malignant melanoma. METHODS: Patients presenting with primary melanoma without evidence of either locoregional or systemic metastasis were considered candidates for SLNB. Selected patients underwent preoperative PET/CT followed by definitive surgical therapy including SLNB with regional lymphadenectomy, where indicated. RESULTS: During a 12-month period 83 patients were identified as having undergone SLNB for melanoma, of which 37 (45%) had preoperative PET/CT. Mean melanoma thickness 1.9 mm and 2.4 mm (PET/CT vs. no PET/CT, p>0.05). 13 (15.6%) patients were found to have lymphatic metastasis at SLNB; nine of these patients underwent PET/CT, only two of these scans were suggestive of lymphatic metastasis (positive predictive value 24%, negative predictive value 76%). PET/CT revealed no unheralded metastatic disease but did identify a second occult malignancy in 4 (10.8%) patients undergoing therapy for melanoma. CONCLUSIONS: The results of this study do not support the use of PET/CT in patients undergoing SLNB for melanoma. SLNB appears to be a more sensitive staging modality in the detection of lymphatic metastasis; however PET/CT may have a future role as a screening tool for malignancy.

Diagnosis, Differential↗
PubMed2005

The role of sentinel lymph node biopsy in ductal carcinoma in situ.

AIM: To review the role of sentinel lymph node (SLN) biopsy in the surgical management of patients with ductal carcinoma in situ (DCIS). METHODS: A search was conducted of Medline and the National Library of Medicine to identify key articles concerning DCIS, SLN biopsy (SLNB) and axillary dissection. Further relevant articles were obtained from the references cited in the literature. RESULTS: Up to 20% of patients with a core biopsy diagnosis of DCIS will be later up-staged based on an invasive component identified on the excision specimen. Quality assurance in breast screening programmes requires minimally invasive pre-operative diagnosis and also axillary sampling in the case of documented invasive disease. As an effective and validated procedure, SLNB represents a paradigm shift in the surgical management of the axilla for patients with invasive breast cancer. It remains undefined which, if any, subgroups of patients with DCIS should undergo SLNB. CONCLUSION: Axillary lymphadenectomy is an overtreatment for patients with DCIS. Performing a SLNB during the initial procedure may avoid a second operation in some DCIS patients who are diagnosed with occult invasive disease at their definitive operation. When predictors of hidden invasive disease are clarified by further study, SLNB may be used in the management of selected high-risk DCIS patients.

Axilla↗
PubMed2005

Major upper gastrointestinal surgery is associated with an antigen-dependent proinflammatory T cell response.

BACKGROUND: T cells play a central role in the immune response to injury. Oesophageal and pancreatic resections are associated with significant risk of systemic inflammatory response syndrome and sepsis. This study involved a detailed analysis of T cell function in a consecutive cohort of patients undergoing such surgery. METHODS: Twenty-five patients undergoing major oncological upper gastrointestinal surgery were investigated for T cell expression of Fas and the activation markers CD69 and CD25, as well as interleukin (IL) 2, IL-10 and interferon (IFN) gamma responses to stimulation with staphylococcal enterotoxin B (SEB). T cell activation in healthy volunteer peripheral blood mononuclear cells was studied in co-culture with patients' serum, either alone or with cytotoxic T lymphocyte-associated antigen (CTLA) 4, an inhibitor of antigen presentation. RESULTS: T cells expressed significantly raised levels of CD69 and CD25 after surgery, but no change in Fas expression was evident. There was a significant increase in the production of IL-2 after surgery without a concomitant increase in IFN-gamma or IL-10 in response to SEB. Postoperative serum activated healthy volunteer T cells, a response that was inhibited (P = 0.053) by co-incubation with CTLA-4. CONCLUSION: Major surgery results in pan-T cell activation via a serum-mediated antigenic mechanism that is independent of Fas expression. Postoperative T cells are primed for an augmented proinflammatory response to superantigen, sustained for at least 1 week, implicating the adaptive immune system in the development of the postoperative systemic immunoinflammatory state.

Adult↗
PubMed2005

A characterization of anaerobic colonization and associated mucosal adaptations in the undiseased ileal pouch.

INTRODUCTION: The resolution of pouchitis with metronidazole points to an anaerobic aetiology. Pouchitis is mainly seen in patients with ulcerative colitis pouches (UCP). We have recently found that sulphate reducing bacteria (SRB), a species of strict anaerobe, colonize UCP exclusively. Herein, we aimed to correlate levels of different bacterial species (including SRB) with mucosal inflammation and morphology. METHODS: Following ethical approval, fresh faecal samples and mucosal biopsies were taken from 9 patients with UCP and 5 patients with familial adenomatous polyposis pouches (FAPP). For the purposes of comparison, faecal samples and mucosal biopsies were also taken from the stomas of 7 of the 9 patients with UC (UCS). Colonization by four types of strict anaerobes (SRB, Clostridium perfringens, Bifidobacteria and Bacteroides) as well as by three types of facultative anaerobes (Enterococci, Coliforms and Lactobacilli) was evaluated. Inflammatory scores and mucosal morphology were assessed histologically in a blinded fashion by a pathologist. RESULTS: In general, strict anaerobes predominated over facultative in the UCP (P = 0.041). SRB were present in UCP exclusively. Even after exclusion of SRB from total bacterial counts, strict anaerobes still predominated. In the UCS, facultative anaerobes predominated. Strict and facultative anaerobes were present at similar levels in the FAPP. Enterococci were present at significantly reduced levels in the UCP when compared with the UCS (P = 0.031). When levels of SRB and other anaerobic species were individually correlated with mucosal inflammation and morphology, no trends were observed. CONCLUSION: We have previously identified that SRB exclusively colonize UCP. In addition we have now identified a novel increase in the strict/facultative anaerobic ratio within the UCP compared to UCS. These stark differences in bacterial colonization, however, appear to have limited impact on mucosal inflammation or morphology.

Adenomatous Polyposis Coli↗
PubMed2004

Minimally invasive parathyroidectomy with operative ultrasound localization of the adenoma.

BACKGROUND: Minimally invasive parathyroidectomy is the procedure of choice for primary hyperparathyroidism due to parathyroid adenoma. Adequate perioperative adenoma localization is essential for this operation. We describe a technique using ultrasound to perform minimally invasive parathyroidectomy. METHODS: 99mTc sestamibi scanning was performed on patients with primary hyperparathyroidism to localize parathyroid adenomas; no intraoperative gamma probe was used. We also performed pre- and intraoperative ultrasound scanning to localize these adenomas. RESULTS: All patients underwent successful localization and removal of their parathyroid adenomas. At follow-up, all patients were well, with calcium within normal limits. CONCLUSION: The use of intraoperative ultrasound facilitates minimally invasive parathyroidectomy and may obviate the need for intraoperative 99mTc sestamibi scanning.

Adenoma↗
PubMed2004

Perioperative topical nitrate and sphincter function in patients undergoing transanal stapled anastomosis: a randomized, placebo-controlled, double-blinded trial.

PURPOSE: The use of transanal stapling devices may impair continence because of digital dilatation and/or instrumentation. This study assessed the effect of pharmacological dilatation of the sphincter prior to stapler insertion. METHODS: A randomized, placebo-controlled, double-blinded study of 60 patients undergoing transanal stapled anastomosis was undertaken. Consenting patients were randomly assigned to receive a single intraoperative dose of topical 0.2 percent nitroglycerin (glyceryl trinitrate) ointment or nitroglycerin-free placebo. All patients were assessed preoperatively and postoperatively by clinical methods (Wexner incontinence scores and examination), anorectal manometry by a station pull-through technique, and endoanal ultrasonography. RESULTS: Intraoperative mean (+/-SEM) resting pressures (mmHg) were significantly reduced by nitroglycerin compared with prenitroglycerin levels (9.9 +/- 0.9 vs. 50.5 +/- 2.7; P = 0.002) or controls (56.0 +/- 3.2; P = 0.001). Twenty-one of the 28 controls (75 percent) but only 4 of the 32 patients in the nitroglycerin group (12.5 percent) required digital dilatation to insert the stapling instrument ( P = 0.003). Squeeze pressures were unaltered by the intervention but mean resting pressures were higher in the nitroglycerin group postoperatively (52.9 +/- 3.2 - 31.6 +/- 1.3 = 21.3 mmHg; 95 percent confidence interval, 14-27). Incontinence scores were lower in the nitroglycerin group at the 3-month (1.1 +/- 0.2 vs. 4.6 +/- 0.3; P = 0.003) and 12-month (0.9 +/- 0.1 vs. 4.4 +/- 0.3; P = 0.002) clinic visits. CONCLUSION: Preoperative nitroglycerin dilatation protects sphincter function in patients undergoing transanal stapled anastomoses.

Administration, Topical↗
PubMed2003

Serum antigen(s) drive the proinflammatory T cell response in acute pancreatitis.

BACKGROUND: Immune cells and cytokines are central to the systemic inflammatory response syndrome and multiple organ failure associated with acute pancreatitis. The specific role of T cells in this response is unclear, and this study focused on evaluating T cell activation and its regulation in patients with acute pancreatitis. METHODS: Peripheral blood samples of 14 patients with acute pancreatitis were obtained within 24 h of the onset of pain, within 48 h and at 1 week. T cell expression of surface markers CD69, CD62L and CD25 was measured. The production of interleukin (IL) 10 and IL-2 in vitro in response to the superantigen Staphylococcus enterotoxin B (SEB) was assessed. Serum samples from these patients were co-cultured with peripheral blood mononuclear cells from volunteers in the presence or absence of cytotoxic T lymphocyte-associated antigen (CTLA) 4 immunoglobulin, a specific inhibitor of antigen-dependent T cell activation. RESULTS: Expression of CD69 was significantly increased in CD3(+) and CD4(+) populations at 48 h and 1 week, and on CD8(+) cells at 1 week. There was a significant increase in the production of SEB-induced IL-2 compared with findings in controls, but no significant IL-10 response. Serum from patients with pancreatitis activated normal T cells. This response was abolished completely by CTLA-4. CONCLUSION: Acute pancreatitis results in the systemic activation of T cells. These cells are primed for a proinflammatory response to antigen stimulation and can be inhibited by antigen-specific T cell blockade. These data indicate that the immunoinflammatory response in acute pancreatitis is fueled by one or more serum antigens and offer prospects for further understanding of the aetiogenesis of pancreatitis.

Acute Disease↗
PubMed2002

Tumor lysis syndrome following endoscopic radiofrequency interstitial thermal ablation of colorectal liver metastases.

Radiofrequency interstitial thermal ablation (RITA) provides a palliative option for patients suffering from metastatic liver disease. This procedure can be performed using a laparoscopic approach with laparoscopic ultrasound used to position the RITA probe. We describe a case of laparoscopic RITA performed for colorectal liver metastasis that was complicated by tumor lysis syndrome (TLS) following treatment. We consider RITA to be a safe procedure, as supported by the literature, but where intracorporal tumor lysis is the treatment goal we believe that the systemic release of tumor products can overwhelm the excretory capacity; therefore, TLS is an inevitable consequence in some patients.

Adult↗
PubMed2002

Emergency surgeon-performed hepatobiliary ultrasonography.

BACKGROUND: Acute hepatobiliary pathology is a common general surgical emergency referral. Diagnosis requires imaging of the biliary tree by ultrasonography. The accuracy and impact of surgeon-performed ultrasonography (SUS) on the diagnosis of emergent hepatobiliary pathology was examined. METHODS: A prospective study, over a 6-month period, enrolled all patients with symptoms or signs of acute hepatobiliary pathology. Patients provided informed consent and underwent both SUS and standard radiology-performed ultrasonography (RUS). SUS was performed using a 2-5-MHz broadband portable ultrasound probe by two surgeons trained in ultrasonography, and RUS using a 2-5-MHz fixed unit. SUS results were correlated with those of RUS and pathological diagnoses. RESULTS: Fifty-three consecutive patients underwent 106 ultrasonographic investigations. SUS agreed with RUS in 50 (94.3 per cent) of 53 patients. SUS accurately detected cholelithiasis in all but two cases and no patient was inaccurately diagnosed as having cholelithiasis at SUS (95.2 per cent sensitivity and 100 per cent specificity). As an overall complementary diagnostic tool SUS provided the correct diagnosis in 96.2 per cent of patients. Time to scan was significantly shorter following SUS (3.1 versus 12.0 h, P < 0.05). CONCLUSION: SUS provides a rapid and accurate diagnosis of emergency hepatobiliary pathology and may contribute to the emergency management of hepatobiliary disease.

Adolescent↗
PubMed2002

Endovascular approach to abdominal aortic aneurysms limits the postoperative systemic immune response.

OBJECTIVES: endovascular repair of abdominal aortic aneurysms (E-AAA) has in recent years developed as an alternative to the conventional open repair (C-AAA). Adverse outcomes following the open approach may relate to immune cell activation and the systemic inflammatory response syndrome (SIRS) and organ failure but the benefits in this respect of the endovascular approach are unclear. This study evaluated this question and focused on T-cell activation and function. DESIGN: prospective clinical study. MATERIALS: twenty patients undergoing abdominal aortic aneurysm repair (12 C-AAA and 8 E-AAA). METHODS: peripheral T-cell expression of surface markers CD69, CD62L and CD25 in vivo and Interleukin 2 (IL-2) and Interleukin-10 (IL-10) responses to the superantigen staphylococcal enterotoxin B (SEB) in vitro were measured preoperatively, 24 h and 1 week postoperatively. RESULTS: there was no significant increase (p=0.23) in the incidence of SIRS in the open compared with the endovascular group. Enhanced T cell activation occurred following C-AAA and this was associated with significantly greater IL-2 production in response to SEB, with no change in IL-10 production. CONCLUSIONS: E-AAA attenuates proinflammatory T-cell changes compared with C-AAA repair. A reduction in T-cell activation and impaired responsiveness to superantigen suggests that the immunological sequelae of the endovascular approach to aneurysm repair is more favourable than after the open approach with potentially less risk of adverse outcomes. Proof of this thesis will require a larger prospective study.

Aged↗
PubMed2000

Biological behaviour and clinical implications of micrometastases.

BACKGROUND: The most important prognostic determinant in cancer is the identification of disseminated tumour burden (metastases). Micrometastases are microscopic (smaller than 2 mm) deposits of malignant cells that are segregated spatially from the primary tumour and depend on neovascular formation (angiogenesis) to propagate. METHODS: The electronic literature (1966 to present) on micrometastases and their implications in malignant melanoma and epithelial cancers was reviewed. RESULTS: Immunohistochemical techniques combined with serial sectioning offer the best accuracy for detection of nodal micrometastases. Molecular techniques should be reserved for blood samples or bone marrow aspirates. Detection of micrometastases in regional lymph nodes and/or bone marrow confers a poor prognosis in epithelial cancers. The concept of sentinel node biopsy combined with serial sectioning and dedicated screening for micrometastases may improve staging procedures. Strategies against angiogenesis may provide novel therapies to induce and maintain micrometastatic dormancy. CONCLUSION: The concept of micrometastases has resulted in a paradigm shift in the staging of epithelial tumours and our overall understanding of malignant processes.

Biopsy, Needle↗
PubMed2000

A central role for CD95 (Fas) in T-cell reactivity after injury.

BACKGROUND: Recent findings indicate that severe injury primes the immune system for an enhanced and lethal proinflammatory cytokine response against bacterial-derived superantigens. This study asked whether this response to injury involves the CD95 (Fas) signaling pathway. METHODS: To assess superantigen-mediated mortality, wild-type (WT) C57BL/6 and Fas-deficient C57BL/6 lpr (-/-) (lpr) mice underwent burn or sham injury and were challenged 2 hours later with staphylococcal enterotoxin B (SEB). Spleen cells from sham and burn WT or lpr mice were stimulated in vitro with SEB to assess injury effects on IL-2, TNF-alpha, and IFN-gamma production. RESULTS: Lpr burn mice survived the SEB challenge (100% survival), while WT burn mice showed a high mortality (17% survival, P < 001, analysis of variance [ANOVA]). Sham lpr or WT mice suffered no mortality to the SEB challenge. In vitro studies demonstrated that burn lpr mice produced significantly less TNF-alpha, IFN-gamma, IL-2 than burn WT mice (P <.01, ANOVA). Burn injury markedly enhanced SEB-stimulated IFN-gamma production by WT spleen cells and CD8+ T cells, while this did not occur in SEB-stimulated lpr spleen cells. CONCLUSIONS: These findings support the hypothesis that the CD95 (Fas) signaling pathway plays an integral role in the injury-induced enhanced and lethal T-cell reactivity against bacterial superantigens.

Analysis of Variance↗
PubMed1999

Nitric oxide synthetase and Helicobacter pylori in patients undergoing appendicectomy.

BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

Adolescent↗
PubMed1999

Circulating granulocyte macrophage colony-stimulating factor in plasma of patients with the systemic inflammatory response syndrome delays neutrophil apoptosis through inhibition of spontaneous reactive oxygen species generation.

In the normal resolution of an acute inflammatory response apoptosis of neutrophils is essential to maintain immune homeostasis and limit inappropriate host tissue damage by decreasing neutrophil tissue load, function, and release of phlogistic reactive oxygen species and proteases. The systemic inflammatory response syndrome (SIRS), a massive pro-inflammatory immune state, is associated with delayed neutrophil apoptosis, however, the systemic circulating factors and intracellular signal transduction pathways important in regulating neutrophil apoptosis in SIRS are poorly described. Neutrophils isolated from patients with SIRS on admission to the intensive care unit showed significantly (p<.01) delayed spontaneous neutrophil apoptosis compared with healthy neutrophils as quantified using annexin V-FITC and terminal deoxyuridine triphosphate (dUTD) nick end labeling (TUNEL) flow cytometry methods. Plasma from SIRS patients markedly (41.5+/-7.2%, p<.01) inhibited apoptosis of healthy neutrophils compared with controls (69.7+/-4.8%) indicating the presence of soluble circulating factors that can modify the expression of neutrophil apoptosis. Various pro-inflammatory (IL-6, granulocyte macrophage colony-simulating factor, interleukin (IL)-1beta, tumor necrosis factor-alpha) mediators, known to modulate neutrophil apoptosis in vitro, were elevated in the plasma of our cohort of SIRS patients compared with controls. However, the anti-apoptotic effect of SIRS plasma was specifically attenuated (75.5%, p<.01) by neutralizing SIRS plasma of granulocyte macrophage-colony-stimulating factor, but not IL-6, IL-1beta, tumor necrosis factor-alpha. Although the anti-inflammatory cytokine IL-10 was elevated in SIRS plasma (median level 7.2 pg/mL), further boosting SIRS plasma with recombinant human IL-10 (10 ng/mL, levels found in septic shock patients) significantly countered (63.8%, p<.01) the inhibitory effect of SIRS plasma on neutrophil apoptosis. Suppression of neutrophil apoptosis was concomitant with delayed spontaneous elevation of reactive oxygen species, quantified as peroxide production, and reversed by addition of neutralizing antibodies to GM-CSF, and recombinant human IL-10 to SIRS plasma. These results identify circulating GM-CSF as a significant inhibitor of neutrophil apoptosis in patients with SIRS, and that this effect can be countered by boosting SIRS plasma with IL-10. GM-CSF and IL-10 appear to modulate neutrophil apoptosis by altering reactive oxygen species generation in neutrophils.

Adolescent↗
PubMed1999

Injury primes the immune system for an enhanced and lethal T-cell response against bacterial superantigen.

We previously reported the high lethality of CD4+ T-cell activation in burn-injured T-cell receptor (TCR) transgenic mice. This suggested to us that T-cells may play a role in the development of the systemic inflammatory response syndrome (SIRS) which can occur after severe injury. In this study, we sought a more clinically relevant model to test the hypothesis that naturally produced bacterial toxins that are known to act as potent polyclonal T-cell activating agents may induce a similar lethal shock-like response in injured, non-TCR transgenic mice. Accordingly, sham- or burn-injured mice were treated with various doses of staphylococcal enterotoxin A (SEA), then observed for 48-hour mortality. We observed 94% and 56% 48-h mortality when burn-injured mice were given 15 microg and 10 microg of SEA, respectively, while neither SEA dose caused mortality in sham-injured mice. The assessment of serum cytokine levels demonstrated significantly elevated interleukin 2 (IL-2) and tumor necrosis factor alpha (TNFalpha) levels when compared to sham mice (P < 0.01). In vitro studies confirmed our in vivo results and also demonstrated elevated levels of interferon gamma (IFNgamma) (P < 0.01). We also observed a novel injury-dependent switch from CD4+ to CD8+ T-cells as the dominant T-cell type producing TNFalpha and IFNgamma in response to SEA stimulation in vitro. Taken together, our findings indicate that injury primes the immune system for an augmented early T-cell response that can result in a lethal shock-like syndrome.

Animals↗