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Biomedical subjects

B T Johnston

Publications and source records attributed to B T Johnston.

At least 19 recordsLinked to original sources
PubMed2006

Circulating markers of prognosis and response to treatment in patients with midgut carcinoid tumours.

BACKGROUND AND AIMS: Midgut carcinoid tumours are uncommon tumours with an unpredictable clinical behaviour and few useful prognostic markers. Somatostatin analogues are widely used in treatment but a survival advantage has not been proven. We analysed features associated with poor prognosis and assessed the clinical implications of the biochemical response to therapy. METHODS: Clinical and biochemical data were collected for patients with midgut carcinoid tumours attending a tertiary referral neuroendocrine clinic from 1978 to 2000. Using death as the end point, univariate and multivariate survival analyses were performed to identify prognostic indicators. The significance of altering biomarkers with therapy was also studied by including repeated measurements of the most prognostic biochemical parameter in a time dependent covariate survival analysis. RESULTS: We identified 139 patients with sufficient data for our analyses. Factors associated with a poor outcome on univariate analysis included: plasma neurokinin A (NKA), urinary 5-hydroxyindolacetic acid output, age, and >/=5 liver metastases. Plasma NKA was the strongest and only independent predictor of outcome on multivariate analysis. Patients in whom NKA continued to rise despite somatostatin analogues had a significantly worse survival than those in whom NKA stabilised or fell (one year survival rate 40% v 87%). Time dependent covariate analysis concluded that survival was better predicted by the most recent plasma NKA value rather than by the initial value. CONCLUSIONS: Plasma NKA is an accurate marker of prognosis for midgut carcinoid tumours. This is the first paper to support a survival advantage in patients in whom plasma NKA is altered by somatostatin analogues.

Adult↗
PubMed2005

An investigation into the role of Bcl-2 in neuroendocrine differentiation.

INTRODUCTION: In addition to its role in apoptosis suppression, Bcl-2 has been reported to be co-expressed with neuroendocrine markers in several tissues, leading to speculation that this oncoprotein may promote neuroendocrine differentiation. AIM: This study investigated whether Bcl-2 modulated neuroendocrine biopeptide expression. METHODS: Levels of chromogranin A, neurone specific enolase, protein gene peptide 9.5, pancreatic polypeptide, and the chromogranin-derived peptides, intervening peptide and vasostatin-1 were examined by immunocytochemistry in rat phaeochromocytoma (PC12) cell lines genetically engineered to over-express Bcl-2 and their mock-transfected controls. Intensity of fluorescence was graded using a semi-quantitative scale from (-) indicating negative expression to (+++) indicating intense positivity. RESULTS: Mann-Whitney U analysis indicated that no significant differences in expression existed between control and Bcl2 over-expressing cell lines for any of the six peptides examined. CONCLUSIONS: The results of this study do not support the hypothesis that Bcl-2 promotes the acquisition of a neuroendocrine phenotype.

Animals↗
PubMed2004

Proposed risk stratification in upper gastrointestinal haemorrhage: is hospitalisation essential?

AIMS: Patients with upper gastrointestinal haemorrhage (UGIH) are usually admitted to hospital regardless of the severity of the bleed. The aim of this study was to identify patients who could be safely managed without hospitalisation and immediate inpatient endoscopy. METHODS: Based on a literature review, a protocol was devised using clinical and laboratory data regarded as being of prognostic value. A retrospective observational study of consecutive patients who attended the emergency department (ED) with UGIH was conducted during one calendar month. RESULTS: Fifty four patients were identified of whom 44 (81%) were admitted. Twelve suffered an adverse event. One of the 10 patients (10%) initially discharged from the ED was later admitted. Strict implementation of the protocol would have resulted in safe discharge of a further 15 patients, (34% of those admitted), and a saving of an estimated 37 bed days per month. CONCLUSIONS: Patients at low risk from UGIH may be identified in the ED. If validated, this protocol may improve patient management and resource utilisation.

Adolescent↗
PubMed2004

Oesophageal pH monitoring is of limited value in the diagnosis of "reflux-cough".

Reflux-cough is a diagnosis based on demonstrating both gastro-oesophageal reflux and a positive response to anti-reflux therapy. The authors sought to determine early and long-term response to therapy in patients with a "positive" 24 h oesophageal pH study, and identify any features which might predict response. Patients with chronic cough were recruited from July 1998 to July 2002. Those with a positive pH study were given dietary advice and an 8-week trial of omeprazole (20 mg b.i.d.). Response was judged after 8 weeks (clinical follow-up), and at long-term follow-up (telephone questionnaire). A total of 146 patients underwent pH monitoring with 82 (56.2%) "positive" studies. Follow-up data was available in 60 patients, with 49 receiving anti-reflux therapy, of which 20 (40.8%) reported a positive treatment response. At long-term follow-up (median 30 months), there was a significantly lower response (14 out of 49, 28.5%), with no significant difference in either acid exposure times (distal/proximal) or symptom correlation between responders and nonresponders at early or long-term follow-up. In conclusion, despite "positive" pH studies, over half of the patients (55.1%) failed to respond to therapy. No features on pH monitoring accurately predicted response. Short-term response did not predict long-term response. The precise role for pH monitoring in the assessment of chronic cough remains to be defined.

Anti-Ulcer Agents↗
PubMed2003

Mortality in Barrett's oesophagus: results from a population based study.

BACKGROUND: Patients with Barrett's oesophagus have an increased risk of oesophageal adenocarcinoma but this cancer only accounts for a small proportion of deaths in these patients. Other causes of death are reportedly raised in this group. We examined cause specific mortality among individuals in a population based Barrett's oesophagus register. METHODS: We constructed a register of all patients diagnosed with columnar mucosa (including specialised intestinal metaplasia) of the oesophagus within Northern Ireland between 1993 and 1999. Deaths occurring within this cohort until 31 December 2000 were identified and mortality rates were compared with the general population. RESULTS: Overall mortality was not raised in Barrett's patients. During 7413 person years of follow up in 2373 patients there were 253 deaths (standardised mortality ratio (SMR) 96 (95% confidence interval (CI) 84-107)). Mortality from oesophageal cancer was raised in patients with specialised intestinal metaplasia (SMR 774 (95% CI 317-1231)) but only 4.7% of patients died from this cancer. Mortality from stroke (SMR 65 (95% CI 37-93)) was significantly lower than the general population while mortality from non-cancerous digestive system diseases was significantly higher (SMR 211 (95% CI 111-311)). Mortality rates from all other causes were similar to those of the general population. CONCLUSIONS: This study demonstrates that the overall mortality rate in patients with Barrett's oesophagus is closely similar to that of the general population. Oesophageal cancer mortality was raised but is an uncommon cause of death in these patients who also appear to have a reduced risk of death from stroke.

Adenocarcinoma↗
PubMed2003

Predictors of therapy resistant asthma: outcome of a systematic evaluation protocol.

BACKGROUND: It has been suggested that asthmatic subjects with persisting symptoms despite adequate maintenance therapy should be systematically evaluated to identify factors contributing to poor control. The aims of this study were to examine the prevalence of these factors in a cohort of sequentially referred poorly controlled asthmatics, and to determine if any factor or combination of factors predicted true therapy resistant asthma (TRA). METHODS: Patients were evaluated using a systematic evaluation protocol including induced sputum analysis, psychiatric assessment, ear, nose and throat examination, pulmonary function testing, high resolution CT scan of the thorax, and 24 hour dual probe ambulatory oesophageal pH monitoring; any identified provoking factor was treated. Asthma was managed according to BTS guidelines. RESULTS: Of 73 subjects who completed the assessment, 39 responded to intervention and 34 had TRA. Subjects with TRA had a greater period of instability, a higher dose of inhaled steroids at referral, more rescue steroid use, and a lower best percentage forced expiratory volume in 1 second (FEV(1)%). Oesophageal reflux, upper airway disease, and psychiatric morbidity were common (57%, 95%, 49%, respectively) but were not more prevalent in either group. Using multivariate logistic regression analysis, inhaled steroid dose >2000 micro g BDP, previous assessment by a respiratory specialist, and initial FEV(1)% of <70% at referral predicted a final diagnosis of TRA. CONCLUSIONS: In poorly controlled asthmatics there is a high prevalence of co-morbidity, identified by detailed systematic assessment, but no difference in prevalence between those who respond to intervention and those with TRA. Targeted treatment of identified co-morbidities has minimal impact on asthma related quality of life in those with therapy resistant disease.

Administration, Inhalation↗
PubMed2001

Effect of bolus consistency on swallowing--does altering consistency help?

The influence of food bolus consistency on the pharyngeal wave during swallowing was investigated using a four-sensor manometry probe in 22 healthy volunteers. Pharyngeal pressures were recorded for 5 ml boluses of water, pudding and buttered bread via a manometry probe placed transnasally. The distal sensor was sited within the upper oesophageal sphincter (UOS); the three proximal sensors were then located 2, 4 and 6 cm above the UOS. The amplitude and timing of the swallow waveforms for pudding and buttered bread were recorded and compared with those for water. Increased bolus viscosity led to increased amplitude of the bolus wave and clearing contraction within the pharynx. In the UOS, increased bolus viscosity was associated with a larger pressure nadir (sub-atmospheric pressure) on opening and intra bolus pressure during transit. Bolus consistency also influenced the coordination of the swallow response with delayed pharyngeal clearance. The putative relevance of these findings to dietary modification for patients with neurological and neuromuscular dysphagia is discussed.

Adult↗
PubMed2001

Repetitive proximal esophageal contractions: a new manometric finding and a possible further link between Parkinson's disease and achalasia.

Repetitive, spontaneous contractions of the proximal esophagus have recently been identified as a feature of achalasia. This article documents similar findings in six patients with Parkinson's disease. Parkinson's disease and achalasia share many common features neurologically. Both have Lewy bodies in the esophageal myenteric plexuses and the substantia nigra, in addition to evidence of degeneration of the dorsal motor nucleus of the vagus. The esophageal features radiologically and manometrically are also similar. Repetitive proximal esophageal contractions may represent another link between these diseases. They have also been reported in scleroderma. We speculate that the common link between all three disease processes may be poor distensibility of the esophagus.

Aged↗
PubMed2001

Manometric abnormalities of the oesophagus in patients with Parkinson's disease.

Dysphagia in Parkinson's disease (PD) is known to correlate with abnormalities of oropharyngeal function. Oesophageal abnormalities have not been previously demonstrated to correlate with dysphagia. The aim of the study was to determine if motor dysfunction of the oesophageal body correlates with dysphagia or disease severity in PD. Twenty-two patients with PD were assessed for the severity of their dysphagia (scale of 1-7) and severity of PD (Hoehn and Yahr scale 1-4). All underwent oesophageal manometry. Dysphagia was present daily in 10 patients (45%). Parkinson's disease was graded as severe (Hoehn and Yahr > or =3) in eight (36%) patients. Oesophageal manometry was abnormal in 16 (73%) patients. Thirteen patients had either complete aperistalsis or multiple simultaneous contractions (diffuse oesophageal spasm). These findings were significantly more common in patients with daily dysphagia (90% vs. 33%; P < 0.005), and were not related to duration or severity of PD. We conclude that the presence of aperistalsis or multiple simultaneous contractions in the oesophagus does correlate with dysphagia and is independent of PD severity or duration. This may reflect selective involvement of either the dorsal motor nucleus of the vagus or the oesophageal myenteric plexus.

Aged↗
PubMed2001

Esophageal investigations in connective tissue disease: which tests are most appropriate?

Our aim was to review the use of esophageal investigations in patients with suspected connective tissue disease (CTD). Forty-seven patients (39 women and 8 men) with suspected CTD were referred for esophageal manometry at the gastrointestinal physiology unit in the Royal Victoria Hospital, Belfast, U.K., over a 10-year period (1987-1997). The mean age was 51.7 years (range = 21-79 years). Chart review was conducted 1 to 10 years after manometry to confirm the final diagnoses: scleroderma was found in 11; CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia), 8; mixed connective tissue disease, 14; Raynaud's alone, 5; and other CTDs, 9. All 47 successfully underwent esophageal manometry. In addition to manometry, 24 underwent gastroscopy; 27, barium meal; and 3, esophageal pH studies. Clinically significant esophageal abnormalities were noted in 8 (33%) on gastroscopy, in 15 (56%) on barium meal, and in 31 (66%) on manometry. Gastroscopy had a significantly lower positivity rate than the others (p < 0.05). Only three patients had pH testing, yet all three pH tests were abnormal. During manometry, abnormal findings were significantly more common in scleroderma-CREST when compared with other diagnoses (89% vs. 50%; p < 0.02). Thirty-three patients reported dysphagia. Abnormal manometry was more likely in these cases (82% vs. 33%; p < 0.02). A high percentage of patients with CTD have significant esophageal motility disorders. Investigations were more likely to be positive with scleroderma-CREST than other CTDs, even if dysphagia was present. Barium meal and manometry are more useful than OGD. pH studies were under-used. There is need for a standardized approach to esophageal investigations in patients with CTDs.

Adult↗
PubMed2000

Basic clinical skills: don't leave teaching to the teaching hospitals.

OBJECTIVE: To compare student perception of teaching in general practice (GP), district general hospitals (DGHs) and teaching hospitals (THs) and their examination results. SETTING: The medical school at Queen's University, Belfast. SUBJECTS AND METHODS: A total of 161 medical and 34 dental students completed an objective structured clinical examination and questionnaire at the end of their second semester of basic skills teaching. They scored the course for teaching style, educational value and enjoyment. Teaching attributes of the tutors were similarly recorded. Students were also asked to quantify how time was used and to comment on the course. INTERVENTIONS: A new programme for teaching first- and second-year students basic clinical skills in the community. RESULTS: Teaching in GP and DGHs was reported to be more educational and enjoyable than in the TH. In GP most time was spent being lectured, in DGHs most time was spent with the patient, and in THs, waiting for the tutor. General practitioners and doctors in DGHs were more likely to model positive teaching attitudes such as showing interest in students and providing feedback. The most common complaints related to insufficient time spent with patients in GP and poor tutor preparation in THs. All teaching sites achieved similar examination results. CONCLUSION: Clinical skills can be taught to medical students early in their curriculum using GP tutors. Student preference was strongly for being taught by GPs rather than in THs. Simple steps such as prior preparation and the locating of a suitable patient could markedly improve student experience both in GP and in hospitals.

Clinical Competence↗
PubMed2000

The effect of lifestyle changes on results of 24-h ambulatory oesophageal pH monitoring.

OBJECTIVES: Twenty-four-hour pH monitoring is the 'gold standard' investigation of gastro-oesophageal reflux disease. It has been suggested that results may be influenced by lifestyle alteration during the study. The aim of this study was to determine the influence of lifestyle alteration and anxiety on outcome in pH monitoring. METHODS: One hundred consecutive patients attending for pH monitoring were recruited. Post-intubation anxiety was quantified (STAI form Y-1). On completion a questionnaire was recorded comprising six questions regarding alteration to eating/drinking (FOOD) (score 0-6) and six regarding posture and activity (ACTIVITY) (score 0-6). The higher the score the greater the alteration of lifestyle. A 10-point visual analogue scale (VAS) scored the degree of distress caused by the experience. pH studies were positive if exposure times at pH < 4 were greater than established normal values or if the Symptom Index was > 50%. Comparisons were made between patients with positive and negative studies regarding FOOD, ACTIVITY, VAS and STAI scores. RESULTS: Patients with positive pH studies had mean FOOD (2 vs 2; P> 0.05), ACTIVITY (2 vs 2; P> 0.05), VAS (3 vs 3; P> 0.05) and STAI (31 vs 32; P> 0.05) scores which were not significantly different from those of patients with negative pH studies. CONCLUSIONS: Lifestyle alteration was minimal in patients undergoing pH monitoring, nor was the experience distressing. There was no difference in lifestyle alteration and anxiety between those with positive and negative pH profiles.

Adolescent↗
PubMed1999

Effects of octreotide on esophageal visceral perception and cerebral evoked potentials induced by balloon distension.

OBJECTIVE: Octreotide, a somatostatin analog, is antinociceptive and increases perception threshold in the rectum. The aim of this study was to determine whether octreotide alters esophageal sensory thresholds and cortical evoked potentials (CEPs) resulting from intraesophageal balloon distension. METHODS: Twelve healthy volunteers (six men and six women, median age 25 yr, range 21-60 yr) underwent a randomized, double-blind, placebo-controlled trial of octreotide 100 microg s.c. versus saline. A 30-mm balloon was inserted 5 cm above the lower esophageal sphincter without topical anesthesia. The balloon was inflated at a rate of 170 cc/s to a maximum of 30 cc in 2 cc steps. Both pressure and volume were recorded. Patients reported first sensation (S1) and maximally tolerated pain (S2). Two cycles were performed both preinjection and 40 min postinjection. Evoked potentials were recorded from Cz to linked ears over 50 balloon inflation cycles (volume = S2). RESULTS: Threshold volume to first sensation (S1) was significantly increased after octreotide injection [median (interquartile range): 24 (14-26) cc vs 13 (9-21) cc, p < 0.02]. No significant alteration in volume causing pain (S2) was noted after octreotide injection [29 (25-30+) cc vs 22 (19-29) cc]. Neither were volumes causing either first sensation [18 (11-24) cc vs 13 (9-18) cc] or pain [27 (23-30) cc vs 23 (21-25) cc] significantly altered by placebo injection. Neither amplitude nor latency of any of the three peaks of the evoked potential recordings differed significantly between postplacebo and postoctreotide recordings. CONCLUSION: Octreotide significantly increased esophageal perception thresholds to balloon distension. It did not alter pain thresholds, nor were cortical evoked potentials to painful stimulation altered in normal subjects.

Adult↗