PubMed Health⌕ Search

Biomedical subjects

K Dolan

Publications and source records attributed to K Dolan.

At least 19 recordsLinked to original sources
PubMed2004

Effect of surveillance of Barrett's oesophagus on the clinical outcome of oesophageal cancer.

BACKGROUND: Surveillance programmes for Barrett's oesophagus have been implemented in an effort to detect oesophageal adenocarcinoma at an earlier and potentially curable stage. The aim of this study was to examine the impact of endoscopic surveillance on the clinical outcome of patients with adenocarcinoma complicating Barrett's oesophagus. METHOD: Consecutive patients who underwent oesophageal resection for high-grade dysplasia or adenocarcinoma arising from Barrett's oesophagus were studied retrospectively. The pathological stage and survival of patients identified as part of a surveillance programme were compared with those of patients presenting with symptomatic adenocarcinoma. RESULTS: Seventeen patients in the surveillance group and 74 in the non-surveillance group underwent oesophagectomy. Disease detected in the surveillance programme was at a significantly earlier stage: 13 of 17 versus 11 of 74 stage 0 or I, three versus 26 stage II, and one versus 37 stage III or IV (P < 0.001). Lymphatic metastases were seen in three of 17 patients in the surveillance group and 42 of 74 who were not under surveillance (P = 0.004). Three-year survival was 80 and 31 per cent respectively (P = 0.008). CONCLUSION: Patients with surveillance-detected adenocarcinoma of the oesophagus are diagnosed at an earlier stage and have a better prognosis than those who present with symptomatic tumours.

Adenocarcinoma↗
PubMed2003

Bilio pancreatic diversion following failure of laparoscopic adjustable gastric banding.

BACKGROUND: This study examines the failure rate with laparoscopic adjustable gastric banding (LABG) and results of band removal with synchronous biliopancreatic diversion without (BPD) or with duodenal switch (BPDDS). METHODS: Failure of LAGB was defined as removal of the band due to insufficient weight loss or a complication. RESULTS: The band was removed in 85 of 1,439 patients (5.9%), most commonly for persistent dysphagia and recurrent slippage. The removal rate and slippage rate decreased from 10.8 and 14.2% to 2.8 and 1.3%, respectively, following introduction of the pars flaccida technique. Fifteen of 27 patients with previous open vertical banded gastroplasty (VBG) required removal of the band. Mean percentage excess weight loss 12 months following open BPD, laparoscopic BPD, open BPDDS, and laparoscopic BPDDS was 44, 37, 35, and 28%, respectively. CONCLUSION: LAGB fails in 6% of patients and removal of the band with synchronous BPD or BPDDS can be performed laparoscopically. Patients with failed primary VBG have a high failure rate with LAGB.

Adult↗
PubMed2003

A comparison of laparoscopic adjustable gastric banding in adolescents and adults.

BACKGROUND: Laparoscopic adjustable gastric banding (AGB) induces effective weight loss in adults, but its efficacy in adolescents has yet to be determined. METHODS: Since 1996, data have been collected prospectively on all patients undergoing laparoscopic AGB procedures performed at our hospital by a single surgeon (G.F.). Patients <20 years old at surgery (adolescents) were compared with- patients >20 years old (adults) who were matched for sex and body mass index (BMI). RESULTS: Seventeen adolescents with a median age of 17 years (range, 12-19) and a BMI of 42.2 kg/m2 (range, 30.3-70.5) were compared to 17 adults with a median age of 41 years (range, 23-70) and a BMI of 41.8 kg/m2 (range, 30.1-71.5). There were no significant differences between the adolescents and the adults in complications or weight loss. The BMI dropped to 30.1 kg/m2 (range, 22.6-39.4) in adolescents and 33.1 kg/m2 (range, 28.4-41.3) in adults at 2-month follow-up. CONCLUSION: Laparoscopic AGB is as effective in adolescents as it is in adults.

Adolescent↗
PubMed2003

Synchronization tomography: a method for three-dimensional localization of phase synchronized neuronal populations in the human brain using magnetoencephalography.

We present a noninvasive technique which allows the anatomical localization of phase synchronized neuronal populations in the human brain with magnetoencephalography. We study phase synchronization between the reconstructed current source density (CSD) of different brain areas as well as between the CSD and muscular activity. We asked four subjects to tap their fingers in synchrony with a rhythmic tone, and to continue tapping at the same rate after the tone was switched off. The phase synchronization behavior of brain areas relevant for movement coordination, inner voice, and time estimation changes drastically when the transition to internal pacing occurs, while their averaged amplitudes remain unchanged. Information of this kind cannot be derived with standard neuroimaging techniques like functional magnetic resonance imaging or positron emission tomography.

Brain↗
PubMed2003

TP53 mutations in malignant and premalignant Barrett's esophagus.

In order to improve the efficacy of endoscopic surveillance of Barrett's esophagus, markers of neoplastic progression in addition to dysplasia are required. The aim of the present study was to assess TP53 mutational analysis as a method of identifying patients with Barrett's esophagus who are at greatest risk of adenocarcinoma, for whom endoscopic surveillance is most appropriate. TP53 mutational analysis was initially performed on premalignant and malignant tissue from 30 patients undergoing esophagectomy for adenocarcinoma, and on premalignant biopsies from 48 patients participating in a Barrett's surveillance program. Surveillance patients were followed up endoscopically and histologically for a median of 5 years following TP53 assessment. Mutational analysis was performed by single-strand conformation polymorphism analysis and direct DNA sequencing. TP53 mutations were detected in 10 of 30 esophageal adenocarcinomas, and were more common in well-differentiated carcinomas. An identical TP53 mutation was detected in carcinoma and adjacent dysplasia. Two patients with premalignant Barrett's esophagus had TP53 mutations and one of these patients developed adenocarcinoma on follow up whilst the other has not yet progressed beyond metaplasia. No patient without TP53 mutation developed high-grade dysplasia or adenocarcinoma. TP53 mutations are detected in 33% of esophageal adenocarcinomas and in 4% of premalignant Barrett's esophagus in patients undergoing endoscopic surveillance. TP53 mutation can be detected before the development of high-grade dysplasia or carcinoma, and may be useful in stratifying the risk of adenocarcinoma in patients with Barrett's esophagus.

Adenocarcinoma↗
PubMed2003

Drug consumption facilities: an update since 2000.

The topic of drug consumption facilities or rooms (DCRs) was reviewed by Dolan, Kimber and others in Harm Reduction Digest 10, published in the September 2000 issue of DAR. As one of the first English language papers on the topic this paper has been cited extensively. Now, 3 years on, these authors and have brought together an international team of experts to revisit the topic. In this update they: (i) highlight where DCRs are operating or under consideration, (ii) review briefly new literature and (iii) discuss future directions. This Digest is a 'must read' for policy makers, advocates and practitioners in the drug field.

Drug Monitoring↗
PubMed2002

Evaluation of POSSUM in patients with oesophageal cancer undergoing resection.

BACKGROUND: The Physiogical and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) has been used to produce a numerical estimate of expected mortality and morbidity after a variety of general surgical procedures. The aim of this study was to evaluate the ability of POSSUM to predict mortality and morbidity in patients undergoing oesophagectomy. METHODS: POSSUM predictor equations for morbidity and mortality were applied retrospectively to 204 patients who had undergone oesophagectomy for cancer. Observed morbidity and mortality rates were compared with rates predicted by POSSUM using the Hosmer-Lemeshow goodness-of-fit test. Evaluation of the discriminative capability of POSSUM predictor equations was performed using receiver-operator characteristic (ROC) curve analysis. RESULTS: The observed and predicted mortality rates were 12.7 and 19.1 per cent respectively, and the respective morbidity rates were 53.4 and 62.3 per cent. However, the POSSUM model showed a poor fit with the data both for the observed 30-day mortality (chi2 = 16.26, P = 0.002) and morbidity (chi2 = 63.14, P < 0.001) using the Hosmer-Lemeshow test. ROC curve analysis revealed that POSSUM had poor predictive accuracy both for mortality (area under curve 0.62) and morbidity (area under curve 0.55). CONCLUSION: These data suggest that POSSUM does not accurately predict mortality and morbidity in patients undergoing oesophagectomy and must be modified.

Adult↗
PubMed2002

Multivariate analysis of clinical, operative and pathologic features of esophageal cancer: who needs adjuvant therapy?

The failure of adjuvant therapy to significantly improve the prognosis of patients undergoing esophago-gastrectomy for cancer may be because of poor patient selection. We sought prognostic factors that would identify those patients who could benefit from adjuvant therapy. Data on 15 possible prognostic factors were prospectively collected on 225 patients undergoing esophago-gastrectomy at a single institution, and univariate and multivariate analyzes performed. T, N, M and overall UICC stage, differentiation, involvement of the circumferential resection margin and number of metastatic of lymph nodes were identified as significant prognostic factors by univariate analysis. Multivariate analysis revealed that the completeness of resection (R-category), ratio of metastatic to total nodes resected and the presence of vascular invasion were independently significant prognostic factors. Following R0 or R1 resection, patients with a metastatic to total lymph node ratio > 0.2 and /or the presence of vascular invasion have a poor prognosis, and the effects of adjuvant therapy in these patients should be studied.

Adult↗
PubMed2001

Does pneumatic dilatation affect the outcome of laparoscopic cardiomyotomy?

BACKGROUND: Controversy surrounds the choice of laparoscopic cardiomyotomy as the primary treatment for achalasia or a second-line treatment following the failure of nonsurgical treatment. Laparoscopic cardiomyotomy can be more difficult technically following pneumatic dilatations. The aim of this study was to compare the outcome obtained with primary laparoscopic cardiomyotomy to that achieved when the procedure is performed following failed pneumatic dilatation. METHODS: Laparoscopic cardiomyotomy was performed in seven patients following a median of four pneumatic dilatations (group A) and in five patients as their primary treatment (group B). Outcome was measured using manometry, a modified DeMeester symptom scoring system, and a quality-of-life questionnaire. RESULTS: There were no significant differences between groups A and B in sex, age, preoperative modified DeMeester score, or mean barrier pressure. Six of seven group A patients had evidence of periesophageal and submucosal fibrosis at surgery, but this condition was not seen in group B patients. The operative time was slightly longer in group A patients. There was no difference in complication rates (one primary hemorrhage in group A and one esophageal perforation in group B), and both groups had a significantly improved modified DeMeester score at 6 weeks and at long-term follow-up (median, 26 months). Eleven of 12 patients said that they would choose laparoscopic cardiomyotomy as their primary treatment if newly diagnosed with achalasia. CONCLUSIONS: Laparoscopic cardiomyotomy is safe and effective as a primary or second-line treatment following pneumatic dilatations in patients with achalasia.

Adult↗
PubMed2001

Pilot randomized controlled study of dexamphetamine substitution for amphetamine dependence.

AIMS: To test the feasibility of conducting a definitive randomized controlled trial of dexamphetamine substitution for amphetamine dependent people and provide preliminary data. DESIGN: An open, two-group pre-post randomized controlled trial. PARTICIPANTS: Forty-one long-term, dependent amphetamine users seeking treatment. INTERVENTION: Twenty subjects were offered weekly counselling. Twenty-one subjects were, in addition, prescribed up to 60 mg dexamphetamine daily. MEASUREMENTS: Immunoassay and mass spectrometric urinalysis techniques were used to identify the presence of amphetamine and methylamphetamine in urine. The Opiate Treatment Index and Severity of Dependence Scale were used to collect pre- and post-self-report data. Subjects were screened using the Composite International Diagnostic Interview. FINDINGS: Reduced street amphetamine use and amphetamine dependence was observed both in subjects prescribed dexamphetamine and subjects receiving counselling only. Treatment subjects appeared more likely to attend counselling. CONCLUSIONS: A definitive randomized controlled trial of dexamphetamine substitution using the techniques and instruments piloted in this study is feasible. Users appeared to be attracted and retained in substitution treatment. The intervention also appeared to be acceptable to clinicians.

Adrenergic Uptake Inhibitors↗
PubMed2000

Detecting the onset of bifurcations and their precursors from noisy data

We study the problem of the detection of noise-induced precursors of periodic motion instabilities in stochastic dynamical systems. In particular, we concentrate on the period-doubling bifurcation. We have developed a statistical method to detect the onset of bifurcations and their precursors based on the previously established topological recurrence technique.

Journal Article↗
PubMed2000

Separate pathways for cellular uptake of ferric and ferrous iron.

Separate pathways for transport of nontransferrin ferric and ferrous iron into tissue cultured cells were demonstrated. Neither the ferric nor ferrous pathway was shared with either zinc or copper. Manganese shared the ferrous pathway but had no effect on cellular uptake of ferric iron. We postulate that ferric iron was transported into cells via beta(3)-integrin and mobilferrin (IMP), whereas ferrous iron uptake was facilitated by divalent metal transporter-1 (DMT-1; Nramp-2). These conclusions were documented by competitive inhibition studies, utilization of a beta(3)-integrin antibody that blocked uptake of ferric but not ferrous iron, development of an anti-DMT-1 antibody that blocked ferrous iron and manganese uptake but not ferric iron, transfection of DMT-1 DNA into tissue culture cells that showed enhanced uptake of ferrous iron and manganese but neither ferric iron nor zinc, hepatic metal concentrations in mk mice showing decreased iron and manganese but not zinc or copper, and data showing that the addition of reducing agents to tissue culture media altered iron binding to proteins of the IMP and DMT-1 pathways. Although these experiments show ferric and ferrous iron can enter cells via different pathways, they do not indicate which pathway is dominant in humans.

Amino Acid Substitution↗
PubMed2000

The evolution of loss of heterozygosity on chromosome 17 during the progression to barrett's adenocarcinoma involves a unique combination of target sites in individual specimens.

We have previously identified thirteen common minimally deleted regions (MRs) on chromosome 17 in twelve Barrett's esophageal adenocarcinoma (BOA) specimens using 41 precisely mapped microsatellite markers (Dunn et al., Oncogene, 17: 987-993, 1999). The aim of the present study has been to identify the earliest sites of loss on this chromosome that arise and persist during the progression to BOA. This has been undertaken by the analysis of multiple carefully microdissected tissue samples from each of five esophagectomy specimens, several of which contained identifiable premalignant tissue. Our data demonstrate a stepwise accumulation of loss in each analyzed specimen, consistent with a single clonal pathway in four specimens and several coexisting pathways in one specimen. Several clonal anomalies (loss preceding heterozygosity and variable intrasample degrees of loss at different markers) were also observed. Within extensively deleted regions of the tumor (seen in three specimens), small deletions were detected in premalignant tissue, predominantly at the site of our identified MRs, and these losses were seen to expand and merge during the progression to BOA. Clonal losses at MRs were first detected in tissue showing early changes histologically, including Barrett's intestinal metaplasia and intermediate-grade dysplasia. Our results provide further support for many of the MRs we have previously identified, thereby adding to evidence for the existence of multiple novel cancer-associated genes on chromosome 17 involved in the development of BOA.

Adenocarcinoma↗
PubMed1999

Multiple target sites of allelic imbalance on chromosome 17 in Barrett's oesophageal cancer.

Twelve Barrett's adenocarcinomas have been analysed for the occurrence of allelic imbalance (LOH) on chromosome 17 using 41 microsatellite markers. This study provides evidence for 13 minimal regions of LOH, six on 17p and seven on 17q. Four of these centre in the vicinity of the known tumour suppressor genes (TSGs) TP53 (17p13.1), NFI (17q11.2), BRCA1 (17q21.1), and a putative TSG (17p13.3). The tumours all displayed relatively small regions of LOH (1-10 cM), and in several tumours extensive regions of LOH were detected. One tumour displayed only two very small regions of LOH; 17p11.2 and 17p13.1. The frequency of allelic imbalance has been calculated based on the LOH encompassing only one minimal region, and based on all the LOH observations. By both evaluations the highest LOH frequencies were found for regions II (p53), III (17p13.1 centromeric to p53), IV (17p12), V (17p11.2) and VII (NF1, 17q11.2). Our data supports the existence of multiple TSGs on chromosome 17 and challenges the view that p53 is the sole target of LOH on 17p in Barrett's adenocarcinoma.

Adenocarcinoma↗
PubMed1999

LOH at the sites of the DCC, APC, and TP53 tumor suppressor genes occurs in Barrett's metaplasia and dysplasia adjacent to adenocarcinoma of the esophagus.

Barrett's esophagus carries a 30- to 100-fold increased risk of adenocarcinoma, which is thought to develop via a metaplasia-dysplasia-carcinoma progression. A common genetic abnormality detected in Barrett's adenocarcinoma is loss of heterozygosity (LOH) at the sites of known or putative tumor suppressor genes, of which there are at least 9 associated with esophageal adenocarcinoma. The aim of this study was to identify at which histological stage of carcinogenesis LOH at these sites occur. Microdissection of multiple paraffin-embedded tissue blocks from 17 esophagogastrectomy specimens of adenocarcinoma arising in Barrett's esophagus yielded areas of metaplasia, low-, intermediate- and high-grade dysplasia, and carcinoma. LOH analysis of microdissected tissues was performed using a double polymerase chain reaction technique with 11 microsatellite primers shown previously to have LOH in at least 30% of esophageal adenocarcinomas. Identical LOH was detected in premalignant and malignant tissues in 4 of 17 patients, and was located at 5q21-q22 (D5S346 primer), 17p11.1-p12 (TCF2 primer), 17p13.1 (TP53 primer), 18q21.1 (detected in colon cancer tumor suppressor gene [DCC] primer), and 18q23-qter (D18S70 primer). These results suggest that LOH at the sites of the DCC, adenomatous polyposis coli (APC), and TP53 tumor suppressor genes occur before the development of adenocarcinoma in Barrett's esophagus, and so merit further study as potential biomarkers of neoplastic progression in patients with Barrett's esophagus undergoing endoscopic and histological surveillance.

Adenocarcinoma↗
PubMed1999

New classification of oesophageal and gastric carcinomas derived from changing patterns in epidemiology.

The current ICD-O classification of carcinomas of the oesophagus and stomach causes epidemiological and clinical confusion. This study compares the epidemiological and clinical features of each subtype and subsite of adenocarcinomas of the oesophagus and stomach, to assess requirements for a new classification of these carcinomas. Data were extracted with appropriate validity checks on all cases of oesophageal and gastric carcinomas identified throughout the period 1974-1993 by the Merseyside and Cheshire Cancer Registry, which covers a population of 2.5 million. The incidence of adenocarcinomas of the lower oesophagus and cardia trebled in males, and doubled in females, whereas adenocarcinoma of the subcardia region of the stomach declined in both sexes. Adenocarcinomas of the lower oesophagus and of the cardia were similar for median age at diagnosis, male to female ratio, percentage of patients who smoked and survival; both were significantly different from carcinomas of the subcardia in these respects. These data imply that adenocarcinomas of the lower oesophagus and cardia are the same disease. A new subsite classification of oesophageal and gastric carcinomas is proposed that includes the gastro-oesophageal junction as a distinct subsite, to facilitate surveillance, management and research.

Adenocarcinoma↗
PubMed1999

Surrogates for finding unstable periodic orbits in noisy data sets.

Recently, searches for unstable periodic orbits in biological and medical applications have become of interest. The motivations for this research range, in order of ascending complexity, from efforts to understand the dynamics of simple sensory neurons, through speculations regarding neural coding, to the hopeful development of new diagnostic and/or control techniques for cardiac and epileptic pathologies. Biological and medical data are, however, noisy and nonstationary. Findings of unstable periodic orbits in such data thus require convincing assessments of their statistical significance. Such tests are accomplished by comparison with surrogate data files designed to test an appropriate null hypothesis. In this paper we test surrogates generated by three different algorithms against correlated noise as well as stable periodic orbits. One of the surrogates is new, and has been specifically designed to preserve the shape of the attractor. We discuss the suitability of these surrogates and argue that the simple shuffled one correctly tests the appropriate null hypothesis.

Journal Article↗