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Biomedical subjects

J Slavin

Publications and source records attributed to J Slavin.

At least 19 recordsLinked to original sources
PubMed2004

Endoscopic retrograde cholangiopancreatography in gallstone-associated acute pancreatitis.

BACKGROUND: Early endoscopic retrograde cholangio-pancreatography with or without endoscopic sphincterotomy (ERCP+/-ES) has been advocated to reduce complications in patients presenting with a severe attack of gallstone-associated acute pancreatitis (GAP). However, a recent trial has reported contradictory results. Importantly, patients with acute cholangitis were excluded suggesting it may be a major confounding factor affecting previous studies. OBJECTIVES: To assess the effectiveness of early ERCP+/-ES compared to conservative management stratified according to severity of disease, concealment of randomisation, acute cholangitis and bilirubin level in the reduction of mortality, morbidity, length of hospitalisation and cost in adults suspected of having GAP. SEARCH STRATEGY: We searched - Cochrane Library (Issue 4 2003), Medline (1966-2004), EMBASE (1980-2004) and LILACS. 'Grey literature' was sought by looking at cited references and hand searched to identify further relevant trials. Conference proceedings of United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) were also hand searched. SELECTION CRITERIA: Randomized controlled trials (RCT) of adult patients, from 15 years old or greater, presenting with gallstone-associated acute pancreatitis (GAP) comparing ERCP +/- ES versus Conservative management within 72 hours of admission. DATA COLLECTION AND ANALYSIS: Data were assessed for quality independently by two reviewers. Wherever appropriate, results were pooled together and sub-grouped by predicted severity of disease. Fixed and random effects models were applied. Sensitivity analysis was performed to test the fragility of results. MAIN RESULTS: Three trials, involving 511 patients, met inclusion criteria. The test for heterogeneity yielded statistically non-significant results (p-value 0.1 to 0.63) suggesting all comparisons were above the established threshold for combinability (p<0.1). Fixed effect and random effect meta-analyses gave identical results. Early ERCP +/- ES was associated with non-significant effect on reduction of mortality in predicted mild (OR = 0.62, 95% CI = 0.27 to 1.41) and severe GAP (OR = 0.62, 95% CI = 0.27 to 1.41). Reduction in complications was non-significant in predicted mild (OR = 0.89, 95% CI = 0.53 to 1.49), but significant in severe GAP (OR = 0.27, 95% CI = 0.14 to 0.53). There was insufficient evidence to draw any conclusions about hospital stay and cost. REVIEWERS' CONCLUSIONS: Odds of having complications are reduced in predicted severe disease by early ERCP +/- ES. This effect was however, non-significant in predicted mild disease and for reduction of mortality in either predicted mild or severe disease. These results are controlled for confounding due to associated acute cholangitis and are robust for clinical and statistical heterogeneity.

Acute Disease↗
PubMed2003

Treatment with Met-RANTES reduces lung injury in caerulein-induced pancreatitis.

BACKGROUND: Severe acute pancreatitis leads to a systemic inflammatory response characterized by widespread leucocyte activation and, as a consequence, distant lung injury. In CC chemokines the first two cysteine residues are adjacent to each other. The aim of this study was to evaluate the effect of Met-RANTES, a CC chemokine receptor antagonist, on pancreatic inflammation and lung injury in caerulein-induced acute pancreatitis in mice. METHODS: Acute pancreatitis was induced in mice by hourly intraperitoneal injection of caerulein. Met-RANTES was administered either 30 min before or 1 h after starting caerulein injections, and pancreatic inflammation and lung injury were assessed. There were five groups of eight mice each including controls. RESULTS: Treatment with Met-RANTES had little effect on caerulein-induced pancreatic damage. Met-RANTES, however, reduced lung injury when given either before administration of caerulein (mean(s.e.m.) lung myeloperoxidase (MPO) 1.47(0.19) versus 3.70(0.86)-fold increase over control, P = 0.024; mean(s.e.m.) microvascular permeability 1.15(0.05) versus 3.57(0.63) lavage to plasma fluorescein isothiocyanate-labelled albumin fluorescence ratio (L/P) per cent, P = 0.002) or after caerulein administration (lung MPO 1.96(0.27) versus 3.65(0.63)-fold increase over control, P = 0.029; microvascular permeability 0.94(0.04) versus 2.85(0.34) L/P per cent, P < 0.001). CONCLUSION: Treatment with Met-RANTES reduces lung damage associated with caerulein-induced pancreatitis in mice. Chemokine receptor antagonists may be of use for the treatment of the systemic complications of acute pancreatitis.

Acute Disease↗
PubMed2003

Thallium-201 scintigraphy--a predictor of tumour necrosis in soft tissue sarcoma following preoperative radiotherapy?

AIM: Thallium-201 (Tl-201) scintigraphy in patients with malignant soft tissue tumours was evaluated to determine whether the images correlated with histological response to preoperative radiotherapy. METHODS: We studied 54 patients, median age 32 (range 17-84) years, with non-metastatic, malignant soft tissue tumours diagnosed between 1996 and 2001. Thirty-eight patients had unoperated tumours and 16 patients had previous incomplete excisions. All patients received preoperative radiotherapy followed by surgery. No patient received chemotherapy as part of their initial management. Qualitative analyses of early phase (30 min) and late phase (4 h) Tl-201 scintigraphic images before and after preoperative radiotherapy were compared with the degree of tumour necrosis determined histologically. RESULTS: In the previously unoperated group, all 38 patients had increased TL-201 uptake in the late phase of scanning prior to radiotherapy suggesting metabolically active tissue. In the previously excised group 11 patients had increased Tl-201 uptake in the late phase of scanning prior to radiotherapy. Following radiotherapy, patients with Tl-201 retention on late phase scans had a lower rate of necrosis than patients with minimal retention, p<0.0001. Following radiotherapy, 28 of 29 patients with minimal uptake on the late phase had 80% or more necrosis, while 24 of 25 patients with increased uptake on the late phase had less than 80% necrosis (p<0.0001). Patients with previously excised tumours who had thallium retention following radiotherapy demonstrated evidence of residual disease at surgery. All patients with incompletely excised tumours who had no thallium retention on late phase scanning after radiotherapy demonstrated no evidence of residual disease at surgery. CONCLUSION: Thallium scintigraphy is a readily available investigative tool, which when used in conjunction with other imaging modalities in the assessment of primary and incompletely excised malignant soft tissue tumours, may predict histological tumour response to preoperative radiotherapy.

Adolescent↗
PubMed2002

Serum amyloid A is a better early predictor of severity than C-reactive protein in acute pancreatitis.

BACKGROUND: Serum amyloid A (SAA) is an early and sensitive marker of the extent of tissue trauma and inflammation. The aim of this study was to compare the early prognostic accuracy of SAA with that of serum C-reactive protein (CRP) in acute pancreatitis. METHODS: In a prospective multicentre trial, plasma SAA and CRP levels were measured in patients with severe and mild acute pancreatitis, and in a control group with acute abdominal pain. Plasma samples were collected on admission and at 6-h intervals for 48 h, every 12 h between 48 and 72 h, then daily for 5 days. Plasma SAA was measured by a new enzyme-linked immunosorbent assay and CRP was measured by immunoturbidometry. RESULTS: There were 137 patients with mild and 35 with severe acute pancreatitis, and 74 control patients. SAA levels were significantly higher in patients with severe acute pancreatitis than in those with mild acute pancreatitis, on admission, at 24 h or less after symptom onset, and subsequently. Whereas plasma CRP concentration was also significantly higher in patients with severe acute pancreatitis on admission, it failed to distinguish mild from severe acute pancreatitis until 30-36 h after symptom onset. SAA levels predicted severity (sensitivity 67 per cent, specificity 70 per cent, negative predictive value 89 per cent, mean(s.d.) area under curve 0.7(0.05)) significantly better than CRP (57 per cent, 60 per cent, 84 per cent, 0.59(0.06) respectively) on admission (P = 0.02) and at 24 h following symptom onset (area under curve 0.65(0.09) versus 0.58(0.09) respectively; P < or = 0.02). CONCLUSION: Plasma SAA concentration is an early marker of severity in acute pancreatitis and is superior to CRP estimation on hospital admission and at 24 h or less after symptom onset. This study suggests that plasma SAA concentration is clinically useful, with the potential to replace CRP in the management of acute pancreatitis.

Abdominal Pain↗
PubMed2002

Levels of the chemokines growth-related oncogene alpha and epithelial neutrophil-activating protein 78 are raised in patients with severe acute pancreatitis.

BACKGROUND: Multiple organ dysfunction syndrome secondary to systemic leucocyte activation is the major cause of death following an attack of acute pancreatitis. Although plasma levels of interleukin (IL) 8 are known to be raised in acute pancreatitis, levels of other CXC chemokines such as growth-related oncogene (GRO) alpha and epithelial neutrophil-activating protein (ENA) 78, which are also potent neutrophil chemoattractants and activators, have not been measured. METHODS: Timed plasma samples were obtained from 51 patients with acute pancreatitis, 27 with a severe attack and 24 with mild disease according to the Atlanta classification. Samples were analysed to determine levels of C-reactive protein (CRP), IL-8, GRO-alpha and ENA-78. RESULTS: Plasma levels of IL-8, GRO-alpha and ENA-78 were increased in patients with severe as opposed to mild acute pancreatitis as early as 24 h following disease onset. Using cut-off levels of 7 pg/ml for IL-8, 70 pg/ml for GRO-alpha and 930 pg/ml for ENA-78, peak levels within the first 24 h of admission had an accuracy of 81, 71 and 87 per cent respectively in predicting the severity of an attack of acute pancreatitis. CONCLUSION: In patients with severe acute pancreatitis plasma levels of GRO-alpha and ENA-78 were raised in addition to those of IL-8, suggesting that all three chemokines are involved in the inflammatory response in this condition.

Acute Disease↗
PubMed2001

Antibiotic prophylaxis in severe acute pancreatitis--what are the facts?

After acute pancreatitis, sepsis secondary to infected pancreatic necrosis is the main cause of late stage death. Routine prophylactic antibiotic use following a severe attack of pancreatitis has been proposed but remains contentious. Three recent randomised controlled studies compared routine antibiotic prophylaxis to no treatment. All three showed reduced sepsis rates and two showed reduced rates of pancreatic infection, but in none was there any effect on operation rate. Only one study, from Finland, has shown any effect on mortality. A feature of the use of prophylactic antibiotics in acute pancreatitis is the increased frequency of drug-resistant or unusual organisms, including fungi, cultured from pancreatic tissue removed at necrosectomy. Mortality may be increased in this group of patients. The aim of antibiotic prophylaxis is a reduced death or operation rate rather than reduced sepsis rates per se and it is possible that the use of prophylactic antibiotics in acute pancreatitis merely masks the underlying disease process without affecting the natural history. There are, thus, too many uncertainties to enable a clear recommendation on routine antibiotic prophylaxis in severe acute pancreatitis. Further well-designed, adequately powered studies are required to establish the role of antibiotic prophylaxis in severe acute pancreatitis.

Acute Disease↗
PubMed2001

The histochemical structure of the deep fascia and its structural response to surgery.

The histochemical structure of the deep fascia and its interface with the underlying muscle was examined in ten pigs. This structure was also evaluated after it had been raised as a fascial flap and in another site after the underlying muscle surface had been disrupted. The deep fascial is a simple structure of densely-packed collagen bundles and elastin fibres, and has hyaluronic acid concentrated on its inner surface, which is in contact with the underlying muscle. There is no specialised lining of this surface of the fascia to account for its gliding properties. The post-surgical specimens demonstrated preservation of the structure of the interface between fascia and muscle, including the retention of the hyaluronic acid lining, if the epimysium was intact. However, if the epimysium was disrupted, the structure of the interface was obliterated.

Animals↗
PubMed2001

Management of necrotizing pancreatitis.

Infection complicating pancreatic necrosis leads to persisting sepsis, multiple organ dysfunction syndrome and accounts for about half the deaths that occur following acute pancreatitis. Severe cases due to gallstones require urgent endoscopic sphincterotomy. Patients with pancreatic necrosis should be followed with serial contrast enhanced computed tomography (CE-CT) and if infection is suspected fine needle aspiration of the necrotic area for bacteriology (FNAB) should be undertaken. Treatment of sterile necrosis should initially be nonoperative. In the presence of infection necrosectomy is indicated. Although traditionally this has been by open surgery, minimally invasive procedures are a promising new alternative. There are many unresolved issues in the management of pancreatic necrosis. These include, the use of antibiotic prophylaxis, the precise indications for and frequency of repeat CE-CT and FNAB, and the role of enteral feeding.

Humans↗
PubMed2001

Adjuvant therapy in pancreatic cancer.

The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic cancer, leading to a dramatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone. The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

Antineoplastic Agents↗
PubMed2001

Changes in hepatitis C-related liver disease in a large clinic population.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant problem in the Australian community. Over the past few years, the number of patients with diagnosed hepatitis C has increased greatly. The aims of the present study were to define the clinical features of a large group of patients with chronic HCV infection and to examine changes occurring in the referral base and epidemiological characteristics of this group since analysis of the first 342 patients in 1994. METHODS: The study included 1,546 consecutive anti-HCV-positive patients who had been referred to St Vincent's Hospital from January 1990 to June 1998. Clinical and laboratory data were collected on all patients. RESULTS: Referrals from general practitioners increased from 31% to 70% of all patients between 1990-1993 and 1994-1998. A history of injecting drug use (IDU) was present in 64% of the patients. While 89% of the IDU group was Australasian born, 49% of those in the sporadic group were born overseas. Cirrhosis was found in 18% of biopsied patients. Age, infection duration, age at infection, Mediterranean or Asian origin and a history of transfusion or lack of HCV risk factors were associated with cirrhosis on univariate analysis. Patient age was the only independent predictor of cirrhosis. CONCLUSION: The majority of patients with HCV are diagnosed in general practice. A risk factor for infection is identified in 82% of patients. While our reported prevalence of cirrhosis may be an overestimate of that in the overall HCV community, the ultimate disease burden is likely to be significant.

Adult↗
PubMed2001

Inflammatory mediators as therapeutic targets in acute pancreatitis.

Multi-organ dysfunction syndrome (MODS) is the primary cause of morbidity and mortality in acute pancreatitis. Recent studies have established the critical role played by inflammatory mediators such as TNFalpha, IL-1beta, IL-6, IL-8, CINC/GROalpha, PAF, IL-10, C5a, ICAM-1 and substance P in acute pancreatitis and the resultant MODS. Potentially, there is a therapeutic window between symptom onset and the development of distant organ damage, when anti-inflammatory therapy may be of use. Elucidation of the key mediators in acute pancreatitis coupled with the discovery of specific inhibitors may make it possible to develop clinically effective anti-inflammatory therapy.

Acute Disease↗
PubMed2000

Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: a multicentre study.

BACKGROUND: There is a pressing clinical requirement for an early simple test of severity in acute pancreatitis. We investigated the use of an assay of trypsinogen activation peptide (TAP). METHODS: We undertook a multicentre study in 246 patients (172 with acute pancreatitis [35 with severe disease], 74 controls). We assessed the predictive value of urinary TAP concentrations measured by a validated competitive immunoassay. We compared the results with those for plasma C-reactive protein and three clinicobiochemical scoring systems. TAP and C-reactive protein concentrations were analysed at set times after symptom onset and compared with the clinicobiochemical systems scores at key times during hospital stay. FINDINGS: At 24 h after symptom onset, the median urinary TAP concentration was 37 nmol/L (IQR 17-110) for severe and 15 nmol/L (5-35) for mild disease (p<0.001). The respective values for plasma C-reactive protein were 24 mg/L (3-34) and 25 mg/L (6-75; p=0.208). The sensitivity, specificity, positive predictive, and negative predictive values of the test to show severe acute pancreatitis compared with mild acute pancreatitis at 24 h were: for TAP (>35 nmol/L), 58%, 73%, 39%, and 86%, respectively, and for C-reactive protein (>150 mg/L), 0%, 90%, 0%, and 75%. 48 h after admission the values for the clinicobiochemical scoring systems were: APACHE II (> or =8), 56%, 64%, 30%, and 85%; Ranson score (> or =3), 89%, 64%, 38%, and 96%; and Glasgow score (> or =3), 77%, 75%, 44%, and 93%. At 48 h, the values for C-reactive protein were 86%, 61%, 37%, and 94% and for TAP were 83%, 72%, 44%, and 94%. Combined testing of C-reactive protein and TAP was not superior to TAP alone for accuracy. INTERPRETATION: Urinary TAP provided accurate severity prediction 24 h after onset of symptoms. This single marker of severity in acute pancreatitis deserves routine clinical application.

Acute Disease↗
PubMed2000

Inflammatory mediators in acute pancreatitis.

Inflammatory mediators play a key role in acute pancreatitis and the resultant multiple organ dysfunction syndrome, which is the primary cause of death in this condition. Recent studies have confirmed the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, PAF, IL-10, C5a, ICAM-1, and substance P. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicaemia, severe burns, and trauma. The delay between the onset of inflammation in the pancreas and the development of the systemic response makes acute pancreatitis an ideal experimental and clinical model with which to study the role of inflammatory mediators and to test novel therapies. Elucidation of the key mediators involved in the pathogenesis of acute pancreatitis will facilitate the development of clinically effective anti-inflammatory therapy.

Acute Disease↗
PubMed2000

Assessment of cellular expression of parathyroid hormone-related protein mRNA and protein in multiple myeloma.

The capacity of multiple myeloma cells to generate parathyroid hormone-related protein (PTHrP) has been examined by in situ assessment of PTHrP mRNA and PTHrP protein in myeloma cells of patients in whom the disease was associated with the development of hypercalcaemia. The presence of PTHrP mRNA was evaluated by in situ hybridization using an antisense riboprobe, and PTHrP by immunohistochemistry using a monoclonal antibody, in archival bone marrow trephine specimens from 17 patients. PTHrP mRNA was detected in myeloma cells in 16 of the 17 patients, indicating a high frequency of PTHrP gene expression in myeloma cells in these subjects. PTHrP protein was, on the other hand, detected in the myeloma cells of only five of these patients. The impact of the mercury-based fixation and decalcification procedure used for processing the bone marrow trephine specimens was assessed to determine the influence of this process on the outcome of the immunohistochemical assay for PTHrP. It was shown that this preparative procedure resulted in a marked reduction of immunohistochemically detectable PTHrP, which provides a possible explanation for the lower frequency of positivity for PTHrP in myeloma cells in the bone marrow specimens. The present findings are consistent with the view that PTHrP can be generated in myeloma cells in vivo, and could contribute to osteolysis and hypercalcaemia, as in patients with cancer.

Aged↗
PubMed2000

Interleukin-8 as an autocrine growth factor for human colon carcinoma cells in vitro.

Cell lines derived from human colon carcinomas secrete interleukin 8 (IL-8) in vitro and this chemokine has also been detected immunohistochemically in human colon carcinoma specimens, in which it is tumour cell associated. In these experiments, IL-8 was shown to comprise an important component of the angiogenic activity of colon carcinoma cell line supernatants. The effect of modulating IL-8 activity upon the growth of the colon carcinoma cell lines HCT116A, HT29 and CaCo2 was investigated. Supplementing endogenously produced IL-8 by recombinant chemokine led to stimulation of cell growth. Neutralization of the effect of endogenously produced IL-8, either with the specific antagonist peptide AcRRWWCR or with blocking anti-IL-8 antibody, resulted in around 50% inhibition of cell growth (P<0.05). All of the colon carcinoma cell lines tested expressed mRNA for both IL-8RA and RB when grown at confluence. At the protein level, all cell lines expressed IL-8RA. Expression of IL-8RB was weak, although increased expression was seen in HCT116A cells as they approached confluence. Antibodies to IL-8RA and RB did not affect proliferation at low cell density but were strongly inhibitory when cells were cultured at a higher density. These data suggest that IL-8 acts as an autocrine growth factor for colon carcinoma cell lines and would support the concept that a similar autocrine loop operates in vivo.

Carcinoma↗
PubMed2000

Adjuvant therapy for pancreatic cancer.

Pancreatic cancer was once considered to be a disease without hope. Advances in regionalisation of treatment in specialist units have resulted in a great improvement in resection outcome. Studies in advanced pancreatic cancer have indicated an advantage for chemotherapy. For 15 years only the GITSG had tested adjuvant therapy in a randomised controlled trial. This small study of only 43 patients suggested a survival benefit for post-operative chemoradiotherapy combined with follow-on chemotherapy. Recently two large trials of over 800 patients, one from the EORTC and the other from ESPAC, have shown no benefit from chemoradiotherapy alone. Results from a Norwegian and from ESPAC suggest that adjuvant chemotherapy (without chemoradiotherapy) prolongs survival. The major randomisation and recruitment centres for ESPAC include Berne, Switzerland, Verona, Italy and Liverpool, UK. The ESPAC-3 Trial plans to recruit 990 patients to definitively answer the chemotherapy question as adjuvant treatment for pancreatic cancer. The new millennium brings hope at last to the most challenging cancer of all--cancer of the pancreas.

Adenocarcinoma↗