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Biomedical subjects

R Sutton

Publications and source records attributed to R Sutton.

At least 109 records · Page 6Linked to original sources
PubMed1998

Allelotype analysis of oesophageal adenocarcinoma: loss of heterozygosity occurs at multiple sites.

Deletions of tumour-suppressor genes can be detected by loss of heterozygosity (LOH) studies, which were performed on 23 cases of adenocarcinoma of the oesophagus, using 120 microsatellite primers covering all non-acrocentric autosomal chromosome arms. The chromosomal arms most frequently demonstrating LOH were 3p (64% of tumours), 5q (45%), 9p (52%), 11p (61%), 13q (50%), 17p (96%), 17q (55%) and 18q (70%). LOH on 3p, 9p, 13q, 17p and 18q occurred mainly within the loci of the VHL, CDKN2, Rb, TP53 and DCC tumour-suppressor genes respectively. LOH on 5q occurred at the sites of the MSH3 mismatch repair gene and the APC tumour-suppressor gene. 11p15.5 and 17q25-qter represented areas of greatest LOH on chromosomes 11p and 17q, and are putative sites of novel tumour-suppressor genes. LOH on 9p was significantly associated with LOH on 5q, and tumours demonstrating LOH at both the CDKN2 (9p21) and MSH3 (5q11-q12) genes had a significantly higher fractional allele loss than those retaining heterozygosity at these sites. Six of nine carcinomas displaying microsatellite alterations also demonstrated LOH at CDKN2, which may be associated with widespread genomic instability. Overall, there are nine sites of LOH associated with oesophageal adenocarcinoma.

Adenocarcinoma↗
PubMed1998

Acute pancreatitis: the substantial human and financial costs.

A greater understanding of the natural history of acute pancreatitis combined with greatly improved radiological imaging has led to improvement in the hospital mortality from acute pancreatitis, from around 25-30% to 6-10% in the past 30 years. Moreover, it is now recognised that the first phase of severe acute phase pancreatitis is a systemic inflammatory response syndrome (SIRS), during which multiple organ failure and death often supervene. Survival into the second phase may be accompanied by local complications, such as infected pancreatic necrosis, which may be prevented by prophylactic antibiotics and treated by judicious surgery. Intensive care unit costs can be substantial, but might be justified because of the excellent quality of life of survivors. Reduction in multiple organ failure by agents such as lexipafant, an antagonist of platelet activating factor (PAF) (which plays a critical role in generating the SIRS), may contribute to intensive care unit cost containment, as well as reducing the incidence of local complications and deaths from acute pancreatitis. A further improvement in the human and financial costs also requires the centralisation of the management of patients with severe acute pancreatitis, to single hospital units whose concentrated expertise equips them to intervene most effectively in what is still recognised as a highly complex disease.

Acute Disease↗
PubMed1998

Abnormal ventricular activation and repolarisation during dobutamine stress echocardiography in coronary artery disease.

OBJECTIVE: To assess possible ECG changes caused by dobutamine stress and their relation to wall motion disturbances in patients with coronary artery disease. DESIGN: Prospective recording and analysis of 12 lead ECG at rest and during each stage of dobutamine stress echocardiography, and correlation with wall motion changes. SETTING: A tertiary referral centre for cardiac disease equipped with non-invasive facilities for pharmacological stress tests. SUBJECTS: 27 patients, mean (SD) age 60 (8) years, with documented evidence of coronary artery disease in whom dobutamine stress echo was clinically indicated, and 17 controls of similar age. RESULTS: In controls, all ECG intervals shortened with increasing heart rate but in the patient group only PR and QT intervals shortened while QRS duration broadened and QTc interval prolonged progressively. In the 27 patients, 16 developed chest pain, 15 with reduced left ventricular long axis systolic excursion (p < 0.001), and all showed reduced peak lengthening rate; ST segment shift appeared in 16, 13 of whom developed chest pain, but did not correlate with reduction of either systolic long axis excursion or peak lengthening rate; QRS duration broadened in 20, 16 with reduction of long axis excursion (p < 0.02) which was more often seen at the septum (p < 0.005); QTc interval prolonged in 19, all of whom had associated reduction of peak long axis lengthening rate (p < 0.02). CONCLUSIONS: QRS duration and QTc interval both normally shorten with dobutamine stress, while in coronary artery disease they both lengthen: changes in QRS duration correlate with systolic and QTc interval with diastolic left ventricular wall motion disturbances. ST segment shift also occurred in most patients, but without consistent correlation with wall motion abnormalities. It was thus less discriminating than the other two abnormalities in this respect.

Aged↗
PubMed1998

Clinical evaluation of a new in-line continuous blood gas monitor.

Two methodologies for obtaining accurate blood gas and electrolyte values during cardiopulmonary bypass (CPB) are traditional laboratory analyzers, which use an electrochemical technology, and continuous in-line monitoring systems, which use a fluorometric and/or spectrophotometric technology. The purpose of the present study was to evaluate the accuracy of a new continuous in-line monitor, the 3M CDI Blood Parameter Monitoring System 500, which provides continuous in-line measurements of pH, PCO2, PO2, potassium (K+), oxygen saturation, hematocrit, hemoglobin, and temperature, during partial or complete CPB. Study parameters included arterial pH, PCO2, PO2, and K+ values. Overall performance was analyzed by calculating the mean difference (expressed as the bias) between the CDI system 500 and the laboratory analyzer for each parameter. The accuracy of the arterial pH, PCO2, and K+ values provided by the CDI system 500 was then evaluated using target values established in the acceptable performance standards for laboratory analyzers from the Clinical Laboratory Improvement Act of 1988 (CLIA '88). The accuracy of the PO2 value provided by the CDI system 500 was evaluated using a target value of +/- 10% of the reference, or laboratory analyzer, value. A prospective multi-center trial was conducted following Institutional Review Board approval. A total of 75 cases was included in the analyses, with over 200 data points from 4 clinical locations. Results for pH, PCO2, and K+ were within the target values established by CLIA '88. pH bias was 0.00 +/- 0.02 pH units. PCO2 bias was -0.3 +/- 3.3 mm Hg. K+ bias was approximately +0.12 +/- 0.31 mmole/l. Results for PO2 were within 10% of the reference value. PO2 bias was 7.5 +/- 13.8 mm Hg. The results of this clinical trial show that the CDI System 500 continuous in-line monitoring system provides values that meet the accuracy standards for laboratory analyzers for arterial pH, PCO2, PO2, and K+.

Bias↗
PubMed1997

Randomised trial of octreotide for long term management of cirrhosis after variceal haemorrhage.

OBJECTIVE: To assess the efficacy of long term octreotide as adjuvant treatment to programmed endoscopic sclerotherapy after acute variceal haemorrhage in cirrhotic portal hypertension. DESIGN: Randomised clinical trial. SETTING: University hospital. SUBJECTS: 32 patients with cirrhotic portal hypertension. INTERVENTIONS: Programmed injection sclerotherapy with subcutaneous octreotide 50 micrograms twice daily for 6 months, or programmed injection sclerotherapy alone. MAIN OUTCOME MEASURES: Episodes of recurrent variceal bleeding and survival. RESULTS: Significantly fewer patients receiving combined octreotide and sclerotherapy had episodes of recurrent variceal bleeding compared with patients given sclerotherapy alone (1/16 v 7/16; P = 0.037, Fisher's exact test), and their survival was significantly improved (P < 0.02, log rank test); this improvement was maintained for 12 months after the end of the study. Combined treatment also resulted in a sustained decrease in portal pressure (median decrease -6.0 mm Hg, interquartile range -10 to -4.75 mm Hg, P = 0.0002) compared with sclerotherapy alone (median increase 1.5 mm Hg, interquartile range 0.25 to 3.25 mm Hg), as well as a significant improvement in liver function as assessed by plasma concentrations of bilirubin, albumin, and alanine aminotransferase and by hepatocyte metabolism of aminopyrine labelled with carbon-14. CONCLUSION: Long term octreotide may be a valuable adjuvant to endoscopic sclerotherapy for acute variceal haemorrhage in cirrhotic portal hypertension.

Acute Disease↗
PubMed1997

Villous adenoma of the distal appendix.

Villous adenoma confined to the distal appendix has not been previously reported in conjunction with acute apendicitis. The presence of an adenoma indicates a need for further investigation due to an association with neoplasia elsewhere.

Acute Disease↗
PubMed1997

Review article: controversy in the therapy of gastro-oesophageal reflux disease--long-term proton pump inhibition or laparoscopic anti-reflux surgery?

The treatment of gastro-oesophageal reflux disease is controversial. Whilst medical treatment is successful in patients with mild to moderate disease, the threshold of severity above which an operation should be contemplated remains a matter for debate. Laparoscopic anti-reflux surgery may be lowering this threshold, as this form of therapy provides several advantages over its open counterpart, but it is not without risk, and few long-term results are available. This article reviews treatment options for reflux disease and examines the relative position of current medical and surgical therapies.

Gastroesophageal Reflux↗
PubMed1997

Right ventricular pressure, dP/dt, and preejection interval during tilt induced vasovagal syncope.

This study examined the potential utility of monitoring right ventricular dP/dt as a means of detecting imminent vasovagal syncope. To assess this possibility, continuous right ventricular pressure measurements were recorded in nine patients during induction of syncope by head-up tilt testing. Findings indicated that arterial pressure tended to fall prior to drop in heart rate. RV pressure exhibited a significant, but very small, fall during tilt. DP/dt max increased by 15-20% during tilt, then fell by a median of 30% from maximum value beginning about 2 minutes prior to syncope. Thus, further investigation of dP/dt as a potential marker of impending vasovagal syncope is warranted.

Adult↗
PubMed1997

Cardiac pacing for vasovagal syncope: a reasonable therapeutic option?

A number of studies have evaluated the effect of cardiac pacing for prevention of tilt induced vasovagal syncope. The findings are relatively consistent. Pacing does not prevent the onset of vasovagal syncope. This is predictable since hypotension (vasodepressor effect) typically occurs prior to bradycardia. However, dual chamber may prolong the presyncopal period in patients with a prominent cardioinhibitory component. Further, the relation of laboratory observations to spontaneous events is uncertain. In the largest retrospective assessment of pacing efficacy, 89% of patients reported improved symptoms and 62% remained free of symptom recurrence over 50 months.

Bradycardia↗
PubMed1997

First steps toward a pacing algorithm for vasovagal syncope.

Vasovagal syncope is commonly associated with an intermediate fall in heart rate. Consequently, it seemed possible that a pacemaker algorithm designed to detect intermediate heart rate falls might prove useful as a diagnostic tool to initiate pacing therapy. Subsequent experience suggests that with such an approach it is still difficult to avoid "false-positive" detection of physiologic heart rate slowing (e.g., sleep). On the other hand, findings from several reports suggest that high rate pacing using this algorithm has proved clinically effective.

Algorithms↗
PubMed1997

Clinical experience with Thera DR rate-drop response pacing algorithm in carotid sinus syndrome and vasovagal syncope. The International Rate-Drop Investigators Group.

This study examined the effectiveness of cardiac pacing using the Thera DR rate-drop response algorithm for prevention of recurrent symptoms in patients with carotid sinus syndrome (CSS) or vasovagal syncope. The algorithm comprises both diagnostic and treatment elements. The diagnostic element consists of a programmable "window" used to identify heart rate changes compatible with an evolving neurally mediated syncopal episode. The treatment arm consists of pacing at a selectable rate and for a programmable duration. Forty-three patients (mean age 53 +/- 20.4 years) with CSS alone (n = 8), CSS in conjunction with vasovagal syncope (n = 4), or vasovagal syncope alone (n = 31) were included. Thirty-nine had recurrent syncope, while the remaining four reported multiple presyncopal events. Prior to pacing, 40 +/- 152 syncopal episodes (range from 1 to approximately 1,000 syncopal events) over the preceding 56 +/- 84.5 months. Postpacing follow-up duration was 204 +/- 172 days. Three patients have been lost to follow-up and in one patient the algorithm was disabled. Among the remaining 39 individuals, 31 (80%) indicated absence or diminished frequency of symptoms, or less severe symptoms. Twenty-three patients (23/29, or 59%) were asymptomatic with respect to syncope or presyncope. Sixteen patients had symptom recurrences. Of these, seven experienced syncope (7/39, or 18%) and 9 (29%) had presyncope: the majority of patients with recurrences (6/7 syncope and 7/9 presyncope) were individuals with a history of vasovagal syncope. Consequently, although symptoms were observed during postpacing follow-up, they appeared to be of reduced frequency and severity. Thus, our findings suggest that a transient period of high rate pacing triggered by the Thera DR rate-drop response algorithm was beneficial in a large proportion of highly symptomatic patients with CSS or vasovagal syncope.

Adolescent↗
PubMed1997

The economics of treating vasovagal syncope.

The economics of treating vasovagal syncope depends on the severity of attacks. In patients with syncope without warning in whom injury is a consideration, a correctly chosen cardiac pacemaker may be warranted. Based on a recent appraisal of the cost effectiveness of dual versus single chamber pacing, it is possible to estimate the economic value of cardiac pacemakers for vasovagal syncope. Findings indicate that an economic argument favors pacing patients with severe vasovagal syncope. However, prospective study examining syncope recurrence rates in paced and nonpaced patients is not currently available.

Cardiac Pacing, Artificial↗
PubMed1997

A multicentre randomised trial comparing octreotide and injection sclerotherapy in the management and outcome of acute variceal haemorrhage.

BACKGROUND: Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined. AIMS: To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage. PATIENTS: Consecutive patients with acute variceal haemorrhage. METHODS: Patients were randomised at endoscopy to receive either a 48 hour intravenous infusion of 50 pg/h octreotide (n = 73), or emergency sclerotherapy (n = 77). RESULTS: Overall control of bleeding and mortality was not significantly different between octreotide (85%, 62 patients) and sclerotherapy (82%, 63 patients) over the 48 hour trial period (relative risk of rebleeding 0.83; 95% confidence interval (CI) 0.38 to 1.82), irrespective of Child's grading or active bleeding at endoscopy. One major complication was observed in the sclerotherapy group (aspiration) and two in the octreotide group (pulmonary oedema, severe paralytic ileus). During 60 days of follow up there was an overall trend towards an increased mortality in the octreotide group which was not statistically significant (relative risk of dying at 60 days 1.91, 95% CI 0.97 to 3.78, p = 0.06). CONCLUSIONS: The results of this study indicate that intravenous octreotide is as effective as injection sclerotherapy in the control of acute variceal bleeding, but further controlled trials are necessary to evaluate the safety of this treatment.

Acute Disease↗
PubMed1997

Hereditary pancreatitis and familial pancreatic cancer.

Important advances in the understanding of pancreatic diseases have taken place through the application of molecular methods in the study of the inherited form of pancreatitis and pancreas cancer. Mutations of the cationic trypsinogen gene have been found to be causative for hereditary pancreatitis with important implications for the molecular pathogenesis of acute and chronic pancreatitis. A variety of cancer syndromes involving the P16 and BRCA2 genes, for example, also lead to pancreatic cancer, but the gene responsible for familial pancreatic cancer has not been identified so far. The establishment of a European Registry of Hereditary Pancreatitis and Pancreatic Cancer (EUROPAC) will facilitate future developments.

Family Health↗
PubMed1997

Endometrial expression of mRNA encoding insulin-like growth factors I and II and IGF-binding proteins 1 and 2 in early pregnant ewes.

The temporal variations in endometrial expression of mRNA encoding insulin-like growth factor I (IGF-I) and IGF-II, and insulin-like growth factor-binding protein 1 (IGFBP-1) and IGFBP-2 were investigated between oestrus and day 20 of pregnancy in ewes. Northern blot analysis of endometrial total RNA revealed major transcripts for IGF-I (7.1 kb), IGF-II (5.8 kb), IGFBP-1 (1.3 kb) and IGFBP-2 (1.7 kb). Some minor transcripts for IGF-II were also detected. The low endometrial expression of mRNA encoding IGF-I at day 15 of pregnancy was used as the reference point for time comparison for expression of mRNA encoding IGF-I, IGF-II and IGFBP-2. The mRNA encoding IGFBP-1 was not quantitated since the gene was expressed only on day 15 of pregnancy. Endometrial expression of mRNA encoding IGF-I was increased (P < 0.05) at oestrus and on day 8 of pregnancy relative to expression on day 15, whereas expression of mRNA encoding IGFBP-2 was decreased (P < 0.05). The major IGF-II transcript was unaffected by day of pregnancy. The temporal variation of the expression of mRNAs encoding IGF-I and IGFBP-2 suggests a role for these factors in the uterine environment during early pregnancy in ewes coinciding with rapid development of the embryo and growth of the uterus in preparation for implantation.

Animals↗
PubMed1997

Astrocytes grafted into rat nucleus basalis magnocellularis immediately after ibotenic acid injection fail to survive and have no effect on functional recovery.

In order to determine if the "trophic" properties of astrocytes makes them appropriate for use as a therapeutic agent to excitotoxic brain damage, adult male rats received grafts of cultured cerebral cortical astrocytes into the NBM immediately after infusion of ibotenic acid into the same structure. Twenty four hours after grafting and every other day for 11 days post surgery, the animals were tested for locomotor activity and habituation in an open field. Animals with NBM lesions had significantly reduced rearing activity as compared to counterparts with no lesions. Nine days after surgery, rats with NBM lesions and astrocyte grafts were as impaired in the acquisition of passive avoidance (PA) as their untreated counterparts. All animals with ibotenic lesions were impaired on PA retention compared to rats with no lesions. There was no difference between animals that had received grafts and those that had not. Fourteen days after grafting, all brains were processed for Nissl stain, acetylcholinesterase (AChE) histochemistry, GFAP immunocytochemistry, and bisbenzamide fluorescent microscopy. Decreases in the number of neurons in the NBM as well as decreases in the density of AChE staining in the ipsilateral cortex (the area of innervation of the NBM cholinergic neurons) was evident in all animals with NBM lesions. In addition, a large number of host reactive astrocytes were seen within the NBM, its vicinity, and in the ipsilateral neocortex. Grafted astrocytes survived and integrated into the host tissue when they were grafted into the brain of intact animals but no living grafted astrocytes were found in animals injected with ibotenate. In this latter case, two weeks after grafting, instead of surviving astrocytes only fluorescent tissue 'masses' were seen in the NBM, surrounded by a cavity. Grafted astrocytes did not have any effect on the extension of the lesion caused by ibotenic acid infusion. These results suggest that the concentration of ibotenic acid used to injure the NBM killed not only the host cholinergic neurons but also the grafted astrocytes. The failure of astrocytes to ameliorate the behavioral deficits caused by ibotenic acid lesions of the NBM may be due to the ibotenic acid creating a lethal environment for the grafted and freshly dissociated, cultured astrocytes.

Acetylcholine↗