Search PubMed⌕ Search

Biomedical subjects

S J Kirk

Publications and source records attributed to S J Kirk.

At least 19 recordsLinked to original sources
PubMed2005

Natural history of asymptomatic bile duct stones at time of cholecystectomy.

OBJECTIVES: There is little data on the natural history of asymptomatic bile duct stones and hence there is uncertainty on the management of asymptomatic bile duct stones discovered incidentally at the time of laparoscopic cholecystectomy. We retrospectively reviewed a group of patients who had previously underwent laparoscopic cholecystectomy, but who did not have a pre-operative suspicion of intra-ductal stones, to determine if any biliary complications had subsequently developed. A group of patients who had no pre-operative suspicion of intra-ductal stones, but routinely underwent intraoperative cholangiogram (IOC) at time of cholecystectomy, served as the control group. METHODS: A telephone questionnaire was completed by each patient's family practitioner in 59 of 79 (75%) patients who underwent laparoscopic cholecystectomy. In the remaining 20 patients additional information was obtained from hospital records and from the central services agency (CSA). These patients had no pre-operative suspicion of bile duct stones and therefore did not undergo an IOC or ERCP. The control group (73 patients) had no pre-operative suspicion of bile duct stones but had a routine IOC performed to define the biliary anatomy. RESULTS: 59 patients were followed up for an average of 57 months (range 30-78 months) after laparoscopic cholecystectomy. None of these patients developed pancreatitis, jaundice, deranged liver function tests (LFT's), or required ERCP or other biliary intervention. In the additional 20 patients where no information was available from the family practitioner, 11 patients had follow up appointments with no documentation of biliary complications or abnormal LFT's. 19 of 20 patients were traceable through the CSA and were all alive. Only 1 patient was untraceable and therefore unknown if biliary complications had developed. In the control group, 4 of 73 (6%) patients had intraductal stones detected and extracted. Thus the prevalence of asymptomatic bile duct stones during the time of cholecystectomy in our population was 6%. CONCLUSIONS: Asymptomatic bile duct stones discovered at the time of cholecystectomy do not appear to cause any biliary complications over a 5-year follow up. Incidental bile duct stones found in patients undergoing laparoscopic cholecystectomy may not need to be removed.

Adult↗
PubMed2004

Radial scar, complex sclerosing lesion and risk of breast cancer. Analysis of 175 cases in Northern Ireland.

BACKGROUND: Controversy exists over the nomenclature and clinical significance of radial scar/complex sclerosing lesion (RS/CSL) of the breast. A retrospective analysis of cases diagnosed from 1988 to 2001 in Northern Ireland was performed to determine if any clinical difference exists between the diagnoses of radial scar and complex sclerosing lesion, and establish if lesions suggestive of RS/CSL require excision and/or follow-up. PATIENTS: Patients with a diagnosis of RS/CSL from 1988 to 2001 were identified from the databases of the pathology laboratories serving specialist breast surgical units and the Northern Ireland Breast Screening Programme. RESULTS: True RS/CSL was confirmed in 175 of 230 cases. There was no difference between RS and CSL regarding associated pathology in the specimen. 16.9% of cases identified at symptomatic clinics were associated with carcinoma in situ, and 15.7% with invasive breast carcinoma, compared to 4.7 and 2.3%, respectively in the screen detected group. One later carcinoma was found. CONCLUSIONS: There is no clinical difference between the entities radial scar and complex sclerosing lesion. RS/CSL require excision due to their association with malignancy. In the absence of any independent risk factor for carcinoma no further follow-up of patients with RS/CSL is required.

Adult↗
PubMed2003

Malignancy-associated changes in lactiferous duct epithelium.

OBJECTIVE: To determine whether cells from histologically normal appearing epithelium of the lactiferous duct from women with a remote ductal lesion in the breast provide any clues indicating the existence of such a lesion. STUDY DESIGN: Tissue sections cut to 4 microns and stained with hematoxylin and eosin were prepared from duct tissue of 20 women with breast lesions and of 20 women free of any such lesion who had undergone mammoplastic procedures or resection for benign reasons. One hundred nuclei were measured from each case. Measures of nuclear deviation from normal were computed, discriminant functions were derived, and multivariate significance tests were conducted. RESULTS: Nuclei from histologically normal appearing regions of lactiferous duct epithelium from women harboring distant lesions exhibited changes in the distribution pattern of their nuclear chromatin, indicating the presence of these lesions. The statistical significance of these changes was documented. The changes were clearly evident in all 20 subjects with lesions and were not observed in 19 of the 20 subjects without lesions. CONCLUSION: The results suggest that studies aimed at detecting malignancy-associated changes in cells collected by ductal lavage might lead to a minimally invasive screening procedure for breast lesions.

Adult↗
PubMed2001

Tumour necrosis factor inhibitors reduce the acute-phase response in hapten-induced colitis.

BACKGROUND: Tumour necrosis factor (TNF) alpha has been implicated in the pathogenesis of inflammatory bowel disease. The aim of this study was to assess the contribution of TNF to the pathogenesis of hapten-induced colitis. METHODS: Colitis was induced in Wistar rats using intracolonic instillation of the hapten trinitrobenzenesulphonic acid (TNBS) in ethanol. Animals were treated with monoclonal anti-TNF antibody (cTN3), an idiotype control antibody (CB0006) or pentoxifylline. Colonic and systemic inflammation was assessed quantitatively. RESULTS: The use of either TNF inhibitor attenuated the acute-phase response in the early stages of colitis. Median (interquartile range (i.q.r.)) alpha 2-macroglobulin levels were reduced in animals pretreated with cTN3 (421 (279-915) micromol/ml) or pentoxifylline (567 (253-1454) micromol/ml) compared with levels in untreated colitic animals (1552 (1406-1998) micromol/ml) (P < 0.001 and P = 0.006, respectively). In established colitis, administration of anti-TNF antibodies resulted in an increase in median (i.q.r.) weight gain (percentage change in body-weight): colitic animals -2.3 (- 5.5 to 9.2) per cent versus cTN3-treated rats 15 (7.5-16.7) per cent; P < 0.05. CONCLUSION: The systemic response to TNBS-induced colitis appears to be at least partially dependent on TNF. This study did not provide evidence to support a role for TNF in the pathogenesis of colonic inflammation in this model. Presented in part to the 86th meeting of the Surgical Research Society in Nottingham, UK, 9-11 July 1997, and published in abstract form as Br J Surg 1997; 84: 1613

Acute-Phase Reaction↗
PubMed2000

Interleukin 10-deficient colitis: new similarities to human inflammatory bowel disease.

BACKGROUND: Interleukin (IL) 10 is a potent anti-inflammatory cytokine. Disruption of the IL-10 gene in C57/Black6 mice results in enterocolitis in the presence of intestinal bacteria. This study investigated gut mucosal barrier function sequentially during the development of colitis in this model. METHODS: Animals were bred in specific pathogen-free conditions and transferred to conventional housing at 4 weeks. Mice were evaluated at 6, 8, 10, 12, 14 and 15 weeks of age. Barrier function was assessed by measuring intestinal permeability and antibody response to systemic endotoxaemia (antibody to the core glycolipid region of lipopolysaccharide; EndoCAb). Colons were harvested and a histological injury score (HIS) was calculated. RESULTS: The HIS increased progressively until 12 weeks, with an associated increase in intestinal permeability, and immunoglobulin (Ig) M and IgG EndoCAb. The HIS correlated positively with both intestinal permeability and IgM and IgG EndoCAb. Intestinal permeability showed a positive correlation with EndoCAb. CONCLUSION: IL-10 knockout mice develop colitis with an associated disturbance in gut mucosal barrier function, as measured by increased permeability and endotoxaemia. The colitis found in the IL-10 knockout mouse shares these histological, physiological and biochemical features with human inflammatory bowel disease and is therefore suitable for therapeutic trials. A measure of endotoxaemia correlated directly with intestinal permeability in this model.

Animals↗
PubMed2000

Probiotic therapy fails to improve gut permeability in a hapten model of colitis.

BACKGROUND: Studies in clinical and experimental inflammatory bowel disease (IBD) have shown disturbances in intestinal bacterial flora with an increase in potentially pathogenic and a decrease in protective organisms. It was hypothesized that Lactobacillus plantarum species 299 (LP299), a probiotic, would ameliorate colitis and improve intestinal permeability in experimental colitis. This study investigated the effect of LP299 in the trinitrobenzenesulfonic acid/ethanol (TNBS/E) rat model of colitis. METHODS: Twelve week old male Wistar rats were randomized to receive rectal instillates of either TNBS/E (n = 48) or saline (n = 16). For the next 7 days the animals were gavaged with 2.5 ml of oat fibre suspension containing 10(9) colony forming units (CFU) of LP299 (LP299/OF), oat fibre suspension alone (OF) or no treatment. At the end of the experiment rats received radiolabelled polyethylene glycol and urine was collected for 24 h to assess permeability. Animals were then anaesthetized and colons were harvested for colon macroscopic scoring (CMS). RESULTS: TNBS/E per rectum resulted in a greater CMS (P < 0.001) and gut permeability (P = 0.006) than saline. Administration of LP299/OF or oat fibre alone did not result in a reduction in CMS or gut permeability when compared to colitic controls. CONCLUSIONS: LP299/OF, when administered after TNBS instillation, does not reduce the severity of colitis or improve gut permeability in this hapten model of colitis.

Animals↗
PubMed2000

Oral administration of inducible nitric oxide synthase inhibitors reduces nitric oxide synthesis but has no effect on the severity of experimental colitis.

BACKGROUND: Increased concentrations of nitrate and nitrite (the breakdown products of nitric oxide) in the serum and faeces of patients with inflammatory bowel disease (IBD) suggests that increased synthesis of nitric oxide occurs in IBD. The aim of this study was to assess aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase, with regard to its effectiveness as a nitric oxide inhibitor and as a modulator of inflammation in trinitrobenzene sulfonic acid (TNBS)-induced colitis. MATERIALS AND METHODS: Colitis was induced in Wistar rats. Selective (AMG) and non-selective (1-nitroso-arginine methyl ester (1-NAME)) inhibitors of nitric oxide synthase were given in the drinking water. Colonic citrulline and arginine concentrations were assessed using high-performance liquid chromatography. The severity of colitis was assessed by a macroscopic scoring system. RESULTS: Both 1-NAME and AMG successfully reduced nitric oxide synthesis. There was no evidence of substrate depletion in the colonic wall. Neither of the agents reduced the severity of colonic inflammation. CONCLUSIONS: Oral administration of nitric oxide synthase inhibitors reduced nitric oxide synthesis in the colonic wall. This study does not provide evidence to support a role for nitric oxide in the pathogenesis of colonic inflammation in TNBS colitis.

Administration, Oral↗
PubMed2000

Pregnancy associated endometriosis with pronounced stromal myxoid change.

A case of endometriosis presenting as a mass in the groin of a pregnant woman is described. The mass increased in size during the pregnancy and the radiological features were suspicious of malignancy. Histological examination showed atrophic glands set in an abundant stroma. This was not typical of normal endometrial stroma but had a pronounced myxoid appearance with areas of decidualization. The atypical site of the endometriosis together with the unusual stromal changes resulted in diagnostic confusion. Although stromal decidualization is well recognized in endometriosis in pregnancy, pronounced myxoid change appears unusual. The myxoid change in this case may be a degenerative phenomenon related to pregnancy.

Adult↗
PubMed1999

Characterization of the Kupffer cell response to exogenous endotoxin in a rodent model of obstructive jaundice.

BACKGROUND: Sepsis and endotoxaemia occur frequently in biliary obstruction. Impaired Kupffer cell endocytosis is implicated in these events. Tumour necrosis factor and interleukin 6, secreted by Kupffer cells, are important mediators of sepsis. Kupffer cell clearance of endotoxin and secretion of cytokines in experimental obstructive jaundice were investigated. METHODS: Wistar rats were randomized to bile duct ligation, sham operation or control. Groups (n = 8) were studied 1 and 3 weeks after operation. Kupffer cell function was assessed using in situ hepatic perfusion. RESULTS: Clearance of endotoxin was significantly depressed 1 week (median (interquartile range) 20.3 (10.5-27.1) per cent) and 3 weeks (22.1 (20.2-23.2) per cent) after bile duct ligation compared with that in respective sham animals (35.5 (29.9-41.6) and 40.9 (37.7-47.0) per cent) and controls (39.5 (37.3-46.8) per cent). Secretion of tumour necrosis factor was significantly greater 1 week (1113.7 (706.5-1436. 8) pg/ml) and 3 weeks (1118.2 (775.7-1484.1) pg/ml) following bile duct ligation compared with that in respective sham animals (114.3 (0-178.5) and 107.6 (63.7-166.4) pg/ml) and controls (0 (0-20.7) pg/ml). Interleukin 6 was not secreted by sham or control animals but was present in the perfusate from jaundiced animals at 1 and 3 weeks (52.5 (9.9-89.5) and 66.2 (60.2-193.1) pg/ml). CONCLUSION: These data demonstrate simultaneous impairment of Kupffer cell clearance of endotoxin and increased secretion of proinflammatory cytokines in experimental obstructive jaundice. These diverse responses may contribute to the development of sepsis-related complications in biliary obstruction.

Animals↗
PubMed1999

Kupffer cell blockade, tumour necrosis factor secretion and survival following endotoxin challenge in experimental biliary obstruction.

BACKGROUND: Gram-negative sepsis and its sequelae frequently complicate invasive procedures in patients with obstructive jaundice. In response to endotoxin, Kupffer cells secrete tumour necrosis factor (TNF), a pivotal early mediator of sepsis. An investigation was carried out into the specific role of Kupffer cell TNF secretion following endotoxin challenge in obstructive jaundice. METHODS: Survival following intraperitoneal administration of endotoxin (2.0, 0.02 and 0.0002 mg per 100 g) was determined in rats following bile duct ligation (BDL) or sham operation. Plasma TNF concentration was quantified following endotoxin administration (0.0002 mg per 100 g) at 1, 2 and 6 h. Subsequently, the effect of Kupffer cell blockade by gadolinium chloride on survival and plasma TNF concentration was assessed. RESULTS: Jaundiced animals showed a significantly increased mortality rate following intraperitoneal injection of endotoxin 2.0 mg per 100 g (BDL 100 per cent versus sham 0 per cent) and 0.02 mg per 100 g (BDL 70 per cent versus sham 0 per cent; P = 0. 002, Fisher's exact test). Median plasma TNF concentration was significantly greater in jaundiced animals 1 h after endotoxin administration (BDL 943 (interquartile range (i.q.r.) 211-3900) pg/ml versus sham 64 (i.q.r. 47-127) pg/ml; P = 0.002, Mann-Whitney U test). Kupffer cell blockade with gadolinium chloride increased the survival rate following endotoxin administration in BDL animals (BDL-GdCl3 100 per cent versus BDL-saline 40 per cent; P = 0.0003, Fisher's exact test) and decreased median plasma levels of TNF (BDL-GdCl3 88 (i.q.r. 0-1065) pg/ml versus BDL-saline 16 550 (1255-29 360) pg/ml; P = 0.002, Mann-Whitney U test). CONCLUSION: Kupffer cell blockade improved survival and suppressed systemic TNF activity after endotoxin challenge. In obstructive jaundice, hypersecretion of TNF by Kupffer cells may supplement systemic cytokine production and be responsible for significant complications.

Animals↗
PubMed1999

Fine needle aspiration cytology (FNAC) of mammary granular cell tumour: a report of three cases.

This report describes the FNAC findings in three cases of granular cell tumour of the breast. The patients comprised two females aged 59 and 62 years and one male aged 28 years. All patients presented with a breast lump which was clinically and radiologically suspicious of malignancy. FNAs yielded moderately cellular specimens which on cytologic examipation consisted of groups of cells and single cells with small regular nuclei and abundant granular cytoplasm. Bare nuclei were also present but these did not have the characteristic bipolar appearance of myoepithelial cells. In two cases there was a granularity to the background. The aspirates were reported as equivocal or atypical, probably benign, and surgical biopsy was performed. Histological examination showed typical benign granular cell tumours with strong positive staining for S-100 protein. Pathologists should be aware that granular cell tumour may occur in or around the breast and should consider this diagnosis in aspirates containing a population of cells with regular nuclei and abundant granular cytoplasm. The main cytologic differential diagnoses are likely to be apocrine cells and histiocytes. The suspicion of a granular cell tumour should be heightened when these features are present in an aspirate from a clinically and radiologically suspicious mass. These cases highlight the role of the triple approach encompassing clinical, radiological and cytological features in the assessment of a breast lesion.

Adult↗
PubMed1997

Tumour necrosis factor and inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF) is a pleiotropic cytokine produced largely by macrophages and T lymphocytes. It has been implicated in the pathogenesis of numerous immunoinflammatory processes. Recently, a number of studies have indicated that anti-TNF antibodies may be of value in the treatment of inflammatory bowel disease. METHODS: The literature is reviewed regarding the role of TNF in the pathogenesis of inflammatory bowel disease and the results of administering TNF inhibitors. RESULTS AND CONCLUSIONS: TNF may have a role in the pathogenesis of inflammatory bowel disease. The effects of TNF inhibitors are complex and incompletely understood. Anti-TNF antibody strategies may have a role in the treatment of acute exacerbations of the disease but are unlikely to be appropriate therapies for long-term management.

Antibodies↗