The future of academic surgery.
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Academic Medical Centers↗
Biomedical subjects
R Sutton
Publications and source records attributed to R Sutton.
Determining the optimal pacing intervention rate for vasovagal syncope.
INTRODUCTION: In this study, patients with rate hysteresis pacemakers implanted for vasovagal syncope were re-studied using serial tilt testing to determine whether, once triggered, pacing was more effective if the intervention rate was higher than the standard rate. METHODS AND RESULTS: Twenty patients (mean age 55.4 years, range 23-81, 14 male) were studied, with randomisation to either initial standard rate (80-90 beats/min) intervention, or to initial high rate (120 beats/min) intervention. Although 18 of the 20 reported complete abolition of syncope since pacing, only 8 patients could be objectively assessed. The respective mean time to tilt down after symptom onset with standard and high rate intervention was 193+/-234s and 185+/-143s, (P>0.05). CONCLUSION: Repeat tilt testing was only of limited value in assessing the benefit of pacing. There was no advantage with high rate intervention in delaying the loss of consciousness (or intolerable symptoms) after the initial onset of symptoms.
Adult↗
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↗
New classification of haemodynamics of vasovagal syncope: beyond the VASIS classification. Analysis of the pre-syncopal phase of the tilt test without and with nitroglycerin challenge. Vasovagal Syncope International Study.
We believe that the pattern of blood pressure response to tilt during the time preceding the development of the vasovagal reaction may provide adjunctive diagnostic information. A group of 101 consecutive patients affected by syncope of uncertain origin underwent passive tilt testing for 45 min at 60 degrees followed, if negative, by oral (sublingual) trinitroglycerin (TNG) 0.4 microg with continuation of the test for 20 min. Three main patterns were observed: the classic (vasovagal) syncope pattern was observed in 36 patients who, during the preparatory phase, had a rapid and full compensatory reflex adaptation to upright position, resulting in stabilization of their blood pressure values until abrupt onset of the vasovagal reaction; the dysautonomic (vasovagal) syncope pattern was observed in 47 patients in whom steady-state adaptation to upright position was not possible. There was thus a progressive fall in their blood pressure until the occurrence of a typical vasovagal reaction; the orthostatic intolerance pattern was observed in 18 patients in whom there was a progressive fall in blood pressure, similar to that of the dysautonomic group, but this was not followed by a clear vasovagal reaction. Compared with the classic, the dysautonomic patients were older, had a higher prevalence of co-morbidities, a very much shorter history of syncopal episodes, and a prevalence of mixed and vasodepressor forms of the VASIS classification. The patients with orthostatic intolerance had clinical characteristics similar to the dysautonmic group but they could not be classified according to the VASIS classification. In conclusion, in patients with syncope, a variety of abnormal responses is observed during tilt testing, suggesting that different syndromes can be diagnosed by the test. A more detailed, although still arbitrary, classification may form the basis of a number of future drug and pacemaker trials, as well as help towards a greater understanding of the different mechanisms of tilt-induced syncope.
Autonomic Nervous System↗
The registry of the European Working Group on Cardiac Pacing (EWGCP). A working group of the European Society of Cardiology.
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Europe↗
'The Italian Protocol': a simplified head-up tilt testing potentiated with oral nitroglycerin to assess patients with unexplained syncope.
Head-up tilt testing potentiated by sublingual nitroglycerin (NTG), advocated by an Italian group, is a simple and safe but still not a standardized, diagnostic tool for the investigation of syncope. In fact, owing to its rapid spread, the original protocol received, often arbitrarily, many subsequent modifications. We now define the best methodology of the test on strictly evidence-based criteria as: stabilization phase of 5 min in the supine position; passive phase of 20 min at a tilt angle of 60 degrees; provocation phase of further 15 min after 400 micrograms NTG sublingual spray. Test interruption is made when the protocol is completed in the absence of symptoms, or there is occurrence of syncope, or occurrence of progressive (> 5 min) orthostatic hypotension. We intend that this protocol, named by us as 'The Italian Protocol', will be accepted as the standard methodology of the tilt test potentiated by sublingual nitrates.
Administration, Oral↗
Syncope.
Syncope is a common clinical presentation. Although most commonly benign, it may herald a pathology with a poor prognosis. The work-up of syncope includes a careful history, physical examination, electrocardiogram, risk stratification, and appropriately directed testing. The key factor in the investigation of syncope is the presence (or absence) of structural heart disease or an abnormal electrocardiogram. The most useful investigation in unexplained syncope with a normal heart is the tilt table test for evaluating predisposition to neurocardiogenic (vasovagal) syncope. In the setting of structural heart disease or an abnormal electrocardiogram, electrophysiologic studies play a more important role. The utility of noninvasive cardiac monitoring for symptom-rhythm correlation may be limited by infrequent symptoms. The availability of external and implantable loop recorders allows prolonged periods of monitoring to increase diagnostic yield. The management of patients with syncope may be complex. Early referral to a cardiac electrophysiologist is warranted in patients who are at high risk.
Electroencephalography↗
Cardioinhibition during tilt testing identifies patients who may benefit from pacing.
UNLABELLED: This study examined whether the various hemodynamic collapse patterns observed during tilt testing in patients with suspected neurocardiogenic syncope are relevant when planning therapy, particularly whether a predominantly cardioinhibitory response predicts a beneficial response from pacing. METHODS: The effects of temporary atrioventricular (A-V) sequential pacing were studied during tilt testing in 34 patients 48.2 +/- 18.5 years of age. The patient population was divided into a cardioinhibitory group (VASIS classes 2A and 2B) or mixed group (VASIS classes 1 and 3) according to their response to baseline tilt testing. The test was then repeated during A-V pacing with rate hysteresis. A positive response to A-V pacing was defined as a > or = 30-second increase between onset of symptoms and syncope, or mitigation of symptoms compared with the baseline tilt test. RESULTS: The study protocol was not successfully completed in three patients. Among the remaining 31 patients, a baseline cardioinhibitory response was observed in 17, and a mixed response in 14 patients. A-V sequential pacing was successful in 13 of 17 patients with a cardioinhibitory response versus 5 of 14 patients with a mixed response (P = 0.024). CONCLUSION: The presence of a predominantly cardioinhibitory collapse pattern (VASIS 2A and 2B) during baseline tilt testing doubled the likelihood of successful temporary A-V sequential pacing, and may identify patients with neurocardiogenic syncope most likely to benefit from permanent dual chamber pacing.
Blood Pressure↗
Respiratory changes in vasovagal syncope.
INTRODUCTION: Respiratory changes accompany the cardiovascular changes during head-up, tilt test-induced vasovagal syncope. METHODS AND RESULTS: Using the 45-minute 60 degrees head-up Westminster protocol, 29 patients were studied (mean age 53.9+/-20.0 years; 19 females). Two groups resulted: tilt-induced vasovagal syncope positive and negative. The cardiorespiratory parameters blood pressure (BP), heart rate (HR), tidal volume, and minute volume were measured. Comparisons of the cardiorespiratory parameters were made within the positive group and negative group, and then between the two groups. There were 14 in the positive group and 15 in the negative group. Baseline measurements were normalized to 1.0. Comparing the late tilt periods between the positive and negative groups, there were differences in BP (P < 0.002), HR (P < 0.002), tidal volume (P < 0.05), and minute volume (P < 0.002). In the positive group comparing early with late intervals: BP 1.11+/-0.09 versus 0.49+/-0.17, P < 0.0001; HR 1.18+/-0.12 versus 0.85+/-0.35, P < 0.009; tidal volume 1.39+/-0.34 versus 2.17+/-1.00, P < 0.015; and minute volume 1.24+/-0.26 versus 3.3+/-2.03, P < 0.0025. There were no comparable cardiorespiratory changes in the negative group. CONCLUSION: There were significant differences in the respiratory and cardiovascular parameters measured between those who were positive and those who were negative for tilt-induced vasovagal syncope. Within the positive group, in addition to the falls in HR and BP, there were significant increases in minute volume and tidal volume during late tilt. This suggests that there may be a role for respiratory sensors in vasovagal syncope that may permit earlier and hence possibly more effective therapy for selected patients.
Adult↗
Pacemaker lead related tricuspid stenosis: a report of two cases.
Only four cases of tricuspid stenosis related to endocardial pacemaker leads have been reported. Two further cases associated with perforation of a tricuspid valve leaflet by a pacemaker lead are presented: a 46 year old woman and a 60 year old man. It is possible that tricuspid valve disease related to endocardial pacemaker and non-thoracotomy defibrillator leads is underrecognized. Diagnosis requires clinical suspicion and the use of Doppler echocardiography. Recent evidence of fibrosis affecting the tricuspid valve in hearts from patients who have had non-thoracotomy defibrillator implants suggests that this problem could be more common in the future.
Echocardiography, Doppler↗
The normal response to prolonged passive head up tilt testing.
OBJECTIVE: To define the responses to head up tilt in a large group of normal adult subjects using the most widely employed protocol for tilt testing. METHODS: 127 normal subjects aged 19-88 years (mean (SD), 49 (20) years) without a previous history of syncope underwent tilt testing at 60 degrees for 45 minutes or until syncope intervened. Blood pressure monitoring was performed with digital photoplethysmography, providing continuous, non-invasive, beat to beat heart rate and pressure measurements. RESULTS: 13% of subjects developed vasovagal syncope after a mean (SD) tilt time of 31.7 (12. 4) minutes (range 8.5-44.9 minutes). Severe cardioinhibition during syncope was observed less often than is reported in patients investigated for syncope. There were no differences in the age or sex distributions of subjects with positive or negative outcomes, or in the proportions with cardioinhibitory and vasodepressor vasovagal syncope compared with previously reported patient populations. Subjects with negative outcomes showed age related differences in heart rate and blood pressure behaviour throughout tilt. CONCLUSIONS: False positive results with tilting appear to be common. This has important implications for the use of diagnostic tilt testing. The magnitude of the heart rate and blood pressure changes observed during negative tilts largely invalidates previously suggested criteria for abnormal non-syncopal outcomes.
Adult↗
Indications, methodology, and classification of results of tilt-table testing.
Tilt-table testing has become an important part of the evaluation of patients with unexplained syncope, although not every patient with vasovagal syncope requires it. Studies have attested to the effectiveness of the technique for providing direct diagnostic evidence of a patient's susceptibility to vasovagal syncope. This article reviews the need for tilt-table testing and the recommended methods for performing a test. In addition, a detailed classification of the hemodynamic patterns of collapse displayed over the course of a tilt-table study is provided. These distinctive collapse patterns document the evolution of a syncopal event and are particularly important to identify because they can influence the selection of therapy.
Autonomic Nervous System↗
Putting it together: a new treatment algorithm for vasovagal syncope and related disorders.
The consensus process that culminated in this symposium established an algorithm to guide the diagnosis and treatment of patients with vasovagal syncope and related disorders. In some patients, the hemodynamic response to standing may identify an abnormality-postural orthostatic tachycardia syndrome or orthostatic hypotension-that can often be treated without further testing. When the response to standing is normal, tilt-table testing may be useful in making the diagnosis of vasovagal syncope and guiding treatment. In some patients, however, the diagnosis is clear from the history, and tilt-table testing may not be necessary. Not all patients with vasovagal syncope need to be treated, and many can be treated effectively with education, reassurance, and a simple increase in dietary salt. In evaluating the results of tilt-table testing, an important consideration is the distinction between vasovagal syncope and the dysautonomic response to tilt characterized by a gradual and progressive decrease in blood pressure that leads to syncope. Current practice patterns suggest that beta blockers, fludrocortisone, and midodrine, are commonly used to treat patients with vasovagal syncope, and patients with the dysautonomic response are generally treated with fludrocortisone and midodrine. Permanent pacing with specialized pacing algorithms should be considered for patients with frequent vasovagal syncope that is refractory to medical therapy. The guidelines proposed here are an amalgam of clinical experience, expert opinion, and research evidence; however, they do not suggest a standard of care for all patients.
Algorithms↗
Usefulness of tilt test-induced patterns of heart rate and blood pressure using a two-stage protocol with glyceryl trinitrate provocation in patients with syncope of unknown origin.
This study assesses the vasovagal collapse pattern changes, i.e, heart rate (HR) and arterial blood pressure (BP) with a 2-stage tilt-test protocol using glyceryl trinitrate (GTN) provocation. With use of the 45-minute 60 degrees head-up Westminster protocol, 102 consecutive patients were studied. Sublingual GTN 300 microg was given to those with a negative passive tilt. Heart rate and BP patterns were classified according to the Vasovagal International Study classification (VASIS) and then compared between those with a positive passive tilt and those with a positive tilt after having been given GTN. Twelve patients did not tolerate tilt testing, and 16 had a negative response despite taking GTN. Thirty-five patients (20 women and 15 men, mean age 45 +/- 21 years [mean +/- SD]) did not take GTN and 38 (26 women and 12 men, mean age 53 +/- 22 years) had positive passive test results. When comparing the VASIS classification between the 2 groups, results showed: type 1, mixed BP and HR decreased without severe bradycardia (31% [passive] vs 54% [with GTN], p = NS); type 2A, BP decreased before HR decreased (20% vs 22%, p = NS); type 2B, HR decreased before or coincident with BP (34% vs 8%, p = 0.003); type 3, BP decreased without HR decrease (9% vs 0%, p = NS); exception 1, chronotropic incompetence (0% vs 13%, p = 0.026); and exception 2, excessive HR increase (6% vs 3%, p = NS). Thus, GTN use increases frequency of positive results from 34% to 73%. Older people with chronotropic incompetence, who may benefit from pacing, were identified. In younger people there was an increase in those with cardioinhibition.
Administration, Sublingual↗
Effect of scaffold attachment region on transgene expression in retrovirus vector-transduced primary T cells and macrophages.
The scaffold attachment region of the human interferon beta gene (IFN-SAR) inserted into a retroviral vector improved transgene expression in human primary CD4+ and CD8+ T cells, and in primary monocytemacrophages. In T cells, expression of the Maloney murine leukemia virus (Mo-MuLV)-based retroviral vectors was high in activated cells but low in resting cells. Addition of the IFN-SAR sequence enhanced vector expression 2- to 10-fold, and the effect was particularly pronounced in resting T cells. In CD33+CD14+CD4+ monocyte-macrophages derived from transduced hematopoietic stem/progenitor cells (HSPCs) in vitro, the IFN-SAR enhanced vector expression three- to sixfold. We have used the IFN-SAR-containing vectors to express the RevM10 gene, a trans-dominant mutant of the human immunodeficiency virus type 1 (HIV-1) rev gene. Compared with a standard retroviral vector, the IFN-SAR-containing vector was significantly (p < 0.01) more potent at inhibiting HIV-1 replication in infected CD4+ peripheral blood lymphocytes. In monocytes, however, addition of the IFN-SAR did not significantly improve antiviral efficacy. To understand better the reason for the strong effect of the SAR on antiviral efficacy in T cells we have studied the expression of HIV, Mo-MuLV, and Mo-MuLV + SAR vectors in resting and activated cells. While the expression of all three vectors was lower in resting compared with activated cells, the kinetics of the decrease in expression were fastest for the Mo-MuLV vector, followed by the HIV vector and then the Mo-MuLV + SAR vector. Thus, higher level expression of the Mo-MuLV + SAR vector relative to wild-type HIV at all stages of T cell activation is the most likely explanation for the strong antiviral efficacy. Overall, this study demonstrates the utility of the IFN-SAR sequence for achieving high-level retroviral vector expression in lymphoid and myeloid hematopoietic cells.
Animals↗
Surface geochemistry of the clay minerals.
Clay minerals are layer type aluminosilicates that figure in terrestrial biogeochemical cycles, in the buffering capacity of the oceans, and in the containment of toxic waste materials. They are also used as lubricants in petroleum extraction and as industrial catalysts for the synthesis of many organic compounds. These applications derive fundamentally from the colloidal size and permanent structural charge of clay mineral particles, which endow them with significant surface reactivity. Unraveling the surface geochemistry of hydrated clay minerals is an abiding, if difficult, topic in earth sciences research. Recent experimental and computational studies that take advantage of new methodologies and basic insights derived from the study of concentrated ionic solutions have begun to clarify the structure of electrical double layers formed on hydrated clay mineral surfaces, particularly those in the interlayer region of swelling 2:1 layer type clay minerals. One emerging trend is that the coordination of interlayer cations with water molecules and clay mineral surface oxygens is governed largely by cation size and charge, similarly to a concentrated ionic solution, but the location of structural charge within a clay layer and the existence of hydrophobic patches on its surface provide important modulations. The larger the interlayer cation, the greater the influence of clay mineral structure and hydrophobicity on the configurations of adsorbed water molecules. This picture extends readily to hydrophobic molecules adsorbed within an interlayer region, with important implications for clay-hydrocarbon interactions and the design of catalysts for organic synthesis.
Journal Article↗
Effect of etilefrine in preventing syncopal recurrence in patients with vasovagal syncope: a double-blind, randomized, placebo-controlled trial. The Vasovagal Syncope International Study.
BACKGROUND: Etilefrine is an alpha-agonist agent with a potent vasoconstrictor effect, which is potentially useful in preventing vasovagal syncope by reducing venous pooling and/or by counteracting reflex arteriolar vasodilatation. The present multicenter, randomized, placebo-controlled study was designed to evaluate the efficacy of this drug for the long-term management of patients with recurrent vasovagal syncope. METHODS AND RESULTS: In the 20 participating centers, 126 patients with recurrent vasovagal syncope (at least 3 episodes in the last 2 years) and a positive baseline head-up tilt response were randomly assigned to placebo (63 patients) or etilefrine at a dosage of 75 mg/d (63 patients) and were followed up for 1 year or until syncope recurred. The primary end-point of the study was the first recurrence of syncope. There were no differences between the 2 study groups in the patients' baseline characteristics. During follow-up, the group treated with etilefrine had a similar incidence of first syncopal recurrence to that of placebo group both in the intention-to-treat analysis (24% versus 24%) and in on- treatment analysis (26% versus 24%). Moreover, the median time to the first syncopal recurrence did not significantly differ between the 2 study groups (106 days in the etilefrine arm and 112 days in the placebo arm). CONCLUSIONS: Oral etilefrine is not superior to placebo in preventing spontaneous episodes of vasovagal syncope. Randomized controlled studies are essential to assess the real usefulness of any proposed therapy for patients with vasovagal syncope.
Adrenergic alpha-Agonists↗
Mode switching for atrial tachyarrhythmias.
Mode switching for atrial tachyarrhythmias is a concept that originated from use of DDI mode and was introduced in the early 1990s to prevent dual-chamber pacemakers from ventricular tracking of rapid atrial rates. This article describes the currently available systems and discusses the advantages and disadvantages of the technique. The results of a preliminary randomized controlled trial of 1 algorithm and plans for a second study are presented.
Algorithms↗