Synthesis of deltorphin I analogues and preliminary characterisation of mu-receptor binding.
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Amino Acid Sequence↗
Biomedical subjects
R Sutton
Publications and source records attributed to R Sutton.
Cardiac pacing.
The symptom most frequently requiring investigation and consideration for cardiac pacing is syncope. This symptom is now receiving more attention than ever, mainly because of the advent of tilt table testing--a simple noninvasive procedure that has substantially reduced the number of syncopal patients remaining undiagnosed. The first part of this review addresses developments in the understanding of syncope, and the latter part covers developments in the understanding and therapy of atrioventricular block and sinus node disease, the management of carotid sinus syndrome, and two possible new indications for pacemaker therapy.
Arrhythmias, Cardiac↗
Regression of columnar lined (Barrett's) oesophagus with continuous omeprazole therapy.
Twenty-three adult patients with a columnar lined (Barrett's) oesophagus are being treated with long-term omeprazole, 40 mg daily. Twelve had never undergone anti-reflux surgery (Group 1), the other eleven having previously had insertion of an Angelchik anti-reflux prosthesis (Group 2). Endoscopy was carried out six months before, immediately before and six months, one year and two years into treatment. Multiple and standardized biopsies were taken at each endoscopy. Results from the two groups were similar. During the 6-month run-in period there was a statistically non-significant increase in the linear extent of the columnar mucosa, but this showed a progressive, statistically significant decrease during the two years of treatment. Other evidence for regression of the Barrett's mucosa includes the emergence of large numbers of macroscopic squamous islands within the abnormal mucosa, an increase in the number of microscopic squamous islands, and microscopic squamous encroachment of the abnormal mucosa at the squamo-columnar junction. Histological assessment showed a reduction in the proportion of sulphomucin-rich intestinal metaplasia, but this only achieved statistical significance in Group 1. The results substantiate the importance of acid in the pathogenesis of Barrett's oesophagus. Omeprazole may have a therapeutic role in bringing about regression of the metaplastic epithelium.
Adult↗
North American Society of Pacing and Electrophysiology policy statement. The NASPE/BPEG defibrillator code.
A new generic code, patterned after and compatible with the NASPE/BPEG Generic Pacemaker Code (NBG Code) was adopted by the NASPE Board of Trustees on January 23, 1993. It was developed by the NASPE Mode Code Committee, including members of the North American Society of Pacing and Electrophysiology (NASPE) and the British Pacing and Electrophysiology Group (BPEG). It is abbreviated as the NBD (for NASPE/BPEG Defibrillator) Code. It is intended for describing the capabilities and operation of implanted cardioverter defibrillators (ICDs) in conversation, record keeping, and device labeling, and incorporates four positions designating: (1) shock location; (2) antitachycardia pacing location; (3) means of tachycardia detection; and (4) antibradycardia pacing location. An additional Short Form, intended only for use in conversation, was defined as a concise means of distinguishing devices capable of shock alone, shock plus antibradycardia pacing, and shock plus antitachycardia and antibradycardia pacing.
Defibrillators, Implantable↗
Assay of gastricsin and individual pepsins in human gastric juice.
AIMS: To develop and validate an analytical procedure for the quantitation of pepsins and gastricsin in human gastric juice and to assess its potential in a controlled gastric secretory study. METHODS: High performance ion-exchange chromatography was used to separate human pepsin 1, 3a, 3b, 3c and gastricsin from gastric juice. Computed chromatographic areas for each enzyme were quantified by relation to a known amount of a secondary standard porcine pepsin. The assay procedure was validated by recovery and analytical precision studies. Gastric secretions after pentagastrin and insulin stimulation from 10 patients with portal hypertension were used to assess the potential of the analytical procedure. RESULTS: The assay precision varied from 1.5 to 9.0% within batch and 7.5 to 18.1% between batch, with about 100% recoveries of porcine pepsin A from human gastric juice over the assay range 0.025-0.5 mg/ml. A fourfold increase in combined pepsin and gastricsin concentration was observed following pentagastrin and insulin stimulation. The mean percentage content of pepsins 3a, 3b, 3c, and 1 in non-stimulated gastric juice were 4%, 72%, 12% and 1.4%, respectively, and did not change significantly after gastric stimulation. An approximate doubling of the percentage of gastricsin (10% to 20%) relative to the pepsins was observed, however, after both insulin and pentagastrin stimulation. CONCLUSIONS: This procedure for quantifying individual human pepsins and gastricsin in gastric juice is simple and reliable. It may be of considerable importance in determining the mechanisms involved in the control and secretion of these digestive enzymes in man, including the effect of anti-ulcer drugs and our understanding of the pathophysiology of peptic ulcer disease.
Chromatography, Ion Exchange↗
Vasodepressor syncope.
Disorders of the autonomic nervous control mechanisms of heart rate and vascular tone may cause syncope. Notably these are carotid sinus and vasovagal syndromes. Knowledge of their aetiology is limited. Each presents cardioinhibition and vasodepression. Pacing offers benefit in cardioinhibition and the mode required is usually dual chamber (DDI) with rate hysteresis. Pacing is unable to control vasodepression. A wide variety of drugs has been proposed to combat the vasodepressor components of these syndromes but none is wholly successful.
Autonomic Nervous System↗
Recommendations for pacing.
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Cardiac Pacing, Artificial↗
A guide to temporary pacing.
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Bradycardia↗
CATS and biochemistry at Wolverhampton Polytechnic.
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Biochemistry↗
Haemodynamic and neurohumoral response in heart failure produced by rapid ventricular pacing.
OBJECTIVE: The aim was to determine the exact sequence of hormone changes during the progression of fluid retention in a canine model of "congestive cardiac failure" induced by rapid right ventricular pacing, and during recovery when pacing is stopped. METHODS: Rapid ventricular pacing at a rate of 250 pulses.min-1 was used in six mongrel dogs with implanted right ventricular pacemakers. Right heart haemodynamics were measured by means of Swan Ganz catheterisation, allowing flow measurement by thermodilution and pressure measurement by external manometry. Plasma renin activity, arginine vasopressin, and atrial natriuretic factor were assayed on venous blood samples by radioimmunoassay. Noradrenaline was assayed by high pressure liquid chromatography. RESULTS: The onset of rapid pacing was accompanied by a fall in cardiac output and a rise in pulmonary arterial, pulmonary capillary wedge, and right atrial pressures. Noradrenaline and atrial natriuretic factor rose. Plasma renin activity showed an initial fall followed by a rise, and arginine vasopressin was unchanged in the first 8 h. When rapid pacing was continued for a further 35 d, clinical signs of fluid retention appeared by day 28, by which time cardiac output had fallen, and central pressures risen further. Atrial natriuretic factor peaked at around 14 d whereas plasma renin activity, arginine vasopressin, and noradrenaline tended to reach a plateau at about d 20 and then to show further increases as clinical signs of fluid retention appeared; this was most marked with plasma renin activity. Cessation of pacing at d 35 caused a rapid reversal (increase) of cardiac output but a more gradual reversal (decrease) of right heart pressures over 5 d; only wedge pressure returned to base line. Arginine vasopressin and plasma renin activity fell rapidly to around 40% of the final pacing levels and reached basal values after 8 h and 48 h respectively. Noradrenaline fell after 8 h and reached basal levels in 5 d. Atrial natriuretic factor fell quickly by 60% after 8 h but remained above basal levels for 5 d. At the end of pacing, body weight fell rapidly in conjunction with a large diuresis. CONCLUSIONS: These findings are compatible with a major role of one or more of renin, vasopressin, and noradrenaline in the pathophysiology of the fluid retention of heart failure; the manifestations are not counteracted by the rise in atrial natriuretic factor.
Animals↗
Development of a rate adaptive pacemaker based on the maximum rate-of-rise of right ventricular pressure (RV dP/dtmax).
The maximum rate of rise of right ventricular pressure (RV dP/dtmax) may change in response to physiological stress and thereby provide an appropriate parameter upon which to base rate adaptive pacing. Initial feasibility testing was carried out in six patients using externally closed loop rate adaptive pacing with a pressure sensing lead (Model 6220) and an investigational VVI pulse generator (Medtronic, Model 2451). During exercise, maximum positive RV dP/dtmax increased from 223 +/- 55 to 405 +/- 181 mmHg.sec.1 (P less than 0.05). Based on these results, rate adaptive pulse generators using maximum positive RV dP/dt were implanted in 12 patients (Medtronic, Model 2503). Exercise treadmill testing in the VVI mode resulted in heart rates ranging from 69 +/- 6 beats/min at rest to 79 +/- 14 beats/min (n = 12; P greater than 0.05). In contrast, VVIR mode pacing rates ranged from 71 +/- 11 beats/min to 115 +/- 24 beats/min (n = 17; P less than 0.05). Holter recording showed heart rates ranging from 51 +/- 6 to 110 +/- 22 beats/min during activities of normal daily living (n = 9; P less than 0.05). Passive postural tilt resulted in rates of 69 +/- 8 beats/min in the supine position increasing to 74 +/- 14 beats/min with 60 degrees upright tilt (n = 16; P greater than 0.05). With up to 5-year follow-up data, there have been no late failures of pacing but one lead showed insulation failure with over- and undersensing after 4.5 years. A number of deficiencies were identified in the prototypes leading to modifications of a subsequent generation of rate responsive pacemaker based on RV dP/dtmax. These initial data demonstrate that rate adaptive pacing based on RV dP/dtmax responds in a physiological manner. This rate responsive system is of particular interest as it is based on a beat-to-beat parameter of cardiac mechanical function.
Activities of Daily Living↗
Pacemaker syndrome: an iatrogenic condition.
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Bradycardia↗
Relative expression of surface IgM, IgD and the Ig-associating alpha(mb-1) and beta(B-29) polypeptide chains.
Membrane immunoglobulins are associated with a transmembrane disulphide-linked heterodimer composed of an alpha-chain (mb-1) and a beta-chain (B-29). The relative surface expression of all of the polypeptide chains comprising the Ig-alpha beta complex has been investigated using surface labelling coprecipitation analysis and two-colour flow cytometric analysis. The main conclusions are that mb-1 and B-29 are B-cell surface markers on immature and mature B cells, and that all components of the surface Ig-alpha beta complex are expressed in stoichiometrically equivalent amounts. Thus the complex was quantitatively precipitated from digitonin lysates of 125I-surface-labelled cells with anti-B-29, anti-mb-1 or anti-Ig. Secondly, by two-colour FACS analysis there was a proportionality between the relative amounts of cell surface mb-1 or B-29 and surface IgM or IgD, but not other B-cell markers (class II, B220, FcR gamma, FcR epsilon). Finally there was an insignificant number of B cells expressing membrane Ig without alpha- and beta-chains, and vice versa. Thus there appears to be a closely controlled relative synthesis and surface expression of all components of the B-cell receptor complex.
Animals↗
myc protooncogenes of wool and hair growth.
The growth of hard keratin fibers such as wool and hair is dependent on the proliferation of cells in the follicle bulb. If the cells leaving the bulb could be induced to undergo an extra division, then fiber growth should increase. The cellular division within the follicle is complex and probably involves one or more growth factors, which act by altering the expression of transcription factors and other nuclear proteins. We propose that the expression of the myc protooncogenes is a central part of this mechanism. In support of this hypothesis we have detected the mRNAs for TGF-beta 1, basic FGF, TGF-alpha, and c-myc in plucked wool follicles using PCR amplification. We have also shown that the TGF-beta 1, TGF-beta 2, TGF-beta 3, EGF, TGF-alpha, basic FGF, N-myc, and c-myc genes are expressed in mouse skin, and we looked for changes during the hair cycle. The PCR data suggest that in whole skin the levels of mRNA for TGF-beta 1, TGF-beta 2, TGF-alpha, and c-myc do not change. In Quackenbush mice the levels for N-myc, TGF-beta 3, and basic FGF mRNA appear to be lower at the end of the hair cycle. We have confirmed in CBA/C57 black mice that lower levels of N-myc mRNA are detected when hair growth ceases in catagen and telogen. To test our hypothesis further and to assess its practical application, we are making transgenic mice in which the N-myc gene is overexpressed in the hair follicle by way of a wool keratin promoter. The transgene consists of 3.3 kb of 5' sequence from an ovine type 1 IF gene, the murine N-myc genomic coding sequence, and an SV40 polyadenylation signal. The native keratin type 1 IF gene is expressed exclusively in the wool follicle, as shown by in situ hybridization. However, in mice the injection of the transgene has resulted in high embryonic mortality and some embryos with large body size and head malformations. Since these mice were not transgenic, this is likely to be an effect of transient expression of the transgene during embryogenesis. The two transgenic mice produced so far have a normal phenotype.
Aging↗
Ultrasound of the common bile duct in patients undergoing cholecystectomy.
One hundred patients undergoing cholecystectomy underwent ultrasonography of the biliary tree on the day prior to surgery. At operation a per-operative cholangiogram was performed unless stones were palpable in the duct. Pre-operative biliary ultrasonography accurately identified dilatation of the common bile duct (sensitivity 96%, specificity 95%) but was less accurate at detecting common duct stones (sensitivity 36%, specificity 98%). Thirty three percent of patients with dilated ducts on ultrasound did not have stones in the duct, while 20% of patients with common duct stones had normal sized ducts. We conclude that ultrasonography alone cannot reliably select patients who require exploration of the common bile duct, or select patients for operative cholangiography. Although pre-operative demonstration of common bile duct dilation is an absolute indication for operative cholangiography, by itself it does not indicate the need for exploration.
Adult↗
Factors influencing the ocular pulse--the heart rate.
Using pneumotonometry combined with a Langham ocular blood-flow system, measurements of pulsatile ocular blood flow (POBF) were performed in eight ocular normotensive patients with implanted cardiac pacemakers, with the subjects assuming both the erect and the supine postures. Sequential measurements of POBF were made at pre-set values of heart rate over the physiological range between 60 and 120 beats/min at intervals of 10 beats/min. With patients in the supine position, measurements of cardiac output and stroke volume indices were also recorded by impedance cardiography. The mean pulse amplitude of the intraocular pressure (the ocular pulse) decreased as heart rate increased, and this change was statistically significant in both postures according to repeated-measures analysis of variance (erect: f = 18.7, P less than 0.0001; supine: f = 18.8, P less than 0.0001). As measured in supine patients following an increase in heart rate, the pulse amplitude decreased in parallel with a decline in stroke volume index (f = 18.8, P less than 0.0001). Up to a level of 90 beats/min, the mean POBF increased with heart rate, but it declined above this rate in both erect and supine postures. At all heart rates, intraocular pressure was higher when subjects were supine than when they stood erect (f = 4.3, P less than 0.001). At lower heart rates of 70 and 80 beats/min, ocular pulse volume and POBF were significantly lower in supine patients than in erect subjects (70 beats/min: t = 3.89, P less than 0.01 vs; t = 3.87, P less than 0.01; 80 beats/min: t = 2.85, P less than 0.05 vs; t = 2.87, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Failure of adjuvant heparin to reduce myocardial ischemia in the early treatment of patients with unstable angina.
Although the efficacy of long-term administration of antithrombotic agents in unstable angina has been established, short-term effects on myocardial ischemia are unknown. A retrospective analysis was performed in 47 patients undergoing three-channel continuous ST segment monitoring as part of a multicenter trial using esmolol in unstable angina, in which 20 patients received a continuous heparin infusion during the initial assessment of chest pain. Concomitant medications included calcium channel blockers, beta-adrenergic blockers, nitrates, and aspirin in the majority of patients. Clinical variables between the heparin and no heparin groups were similar, except for fewer males and fewer total artery occlusions in the heparin group. No significant differences in the incidence or duration of ischemia were found in a 36 +/- 16 hour monitoring period. Forty percent of the heparin group had 35 episodes of ischemia with a mean of 11 +/- 10 minutes per episode and a total ischemic time of 48 +/- 39 minutes per patient with ischemia. Forty-four percent of the no heparin group had 47 episodes of ischemia with a mean of 13 +/- 13 minutes per episode and a total ischemic time of 58 +/- 47 minutes per patient with ischemia. Multiple linear regression analysis to adjust for intergroup differences did not alter the results. Eighty-five percent of all episodes were asymptomatic. Clinical events, such as episodes of chest pain, emergency coronary arteriography, or coronary revascularization, were also similar between groups. Thus the short-term administration of heparin did not alter the incidence or duration of ischemia in patients with unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗