Psychological debriefing. Qualitative research may be more appropriate.
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Biomedical subjects
Publications and source records attributed to A Powell.
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Voltage-gated sodium channels consist of a pore-containing alpha-subunit and one or more auxiliary beta-subunits, which may modulate channel function. We previously demonstrated that sodium channel SNS/PN3 alpha-subunits were decreased in human sensory cell bodies after spinal root avulsion injury, and accumulated at injured nerve terminals in pain states. Using specific antibodies for immunohistochemistry, we have now detected sodium channel beta1 and beta2 subunits in sensory cell bodies within control human postmortem sensory ganglia (78% of small/medium (< or = 50 microm) and 68% of large (> or = 50 microm) cells); their changes in cervical sensory ganglia after avulsion injury paralleled those described for SNS/PN3 alpha-subunits. Our results suggest that alpha- and beta-subunits share common regulatory mechanisms, but present distinct targets for novel analgesics.
Sensory neurones co-express voltage-gated sodium channels that mediate TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) currents, which may contribute to chronic pain after nerve injury. We previously demonstrated that TTX-R channels were decreased acutely in human sensory cell bodies after central axotomy, but accumulated in nerve terminals after peripheral axotomy. We have now studied the TTX-S channels PN1 and Brain III, using specific antibodies for immunohistochemistry, in dorsal root ganglia (DRG) from 10 patients with traumatic central axotomy, nerves from 16 patients with peripheral axotomy, and controls. PN1 showed temporal changes similar to the TTX-R channels in sensory cell bodies of injured DRG. In contrast, Brain III was found only in injured nerves (not control nerves, or control/central axotomy DRG). PNI and Brain III are distinct targets for novel analgesics.
The heparan sulfates are a family of cell-surface and matrix polysaccharides with an incredible degree of structural diversity that are distributed widely in virtually all metazoan organisms. Recent genetic, biochemical and cell-biological studies have led to increased understanding of the biosynthetic mechanisms that produce these complex molecules, as well as their functional versatility in regulating protein activities. The dynamic expression of heparan sulfates with differing sugar sequences suggests a new concept in which the repertoire of sequences produced by a particular cell or tissue is designated its 'heparanome'. This review discusses recent developments and surveys emerging experimental strategies that hold promise for revealing the functional specificity and mechanisms of action of heparan sulfates as multifunctional cell regulators.
PURPOSE: To determine early and late outcomes of transluminal endografting (TE) in patients with abdominal aortic aneurysm (AAA), stratified by predicted risk of procedure-related mortality with conventional operation. MATERIALS AND METHODS: A retrospective study was conducted in consecutive risk-stratified AAA patients undergoing TE at a not-for-profit cardiovascular referral center from March 1994 through November 2000 with follow-up through February 2001. With use of conventional risk strata (0 = low, 1 = minimal, 2 = moderate, and 3 = high), predicted procedure-related mortalities were 0%-1% in stratum 0 (n = 40), 1%-3% in stratum 1 (n = 118), 3%-8% in stratum 2 (n = 116), and 8%-30% in stratum 3 (n = 31). Main outcome measures were: (i) TE procedural success, (ii) procedure-related mortality, (iii) major nonfatal complications, (iv) composite adverse outcome (ii + iii), (v) length of stay (LOS), (vi) freedom from AAA rupture, (vii) late survival, (viii) late complications, and (ix) endoleaks and their classification and management. RESULTS: Women were significantly less likely than men to qualify for and undergo endografting: 24 of 91 (26.4%) women underwent TE, compared to 281 of 684 (41.1%) men. Of 305 attempted TE procedures, 291 (95.4%) were successful, four (1.3%) were urgently converted to open repair, and 10 (3.3%) were aborted. Procedure-related mortalities occurred in eight cases (2.6%) overall and one of 40 (2.5%), one of 118 (0.8%), four of 116 (3.4%), and two of 31 (6.5%) cases for risk strata 0-3, respectively. Perioperative survivors were significantly younger than nonsurvivors (74.3 y +/- 9 vs 81.6 y +/- 5.1; P =.0087). Forty-six patients (15.1%) had major complications. Composite adverse outcome was worse for patients in stratum 3 than those in stratum 1 (P =.0296) and those in strata 0, 1, and 2 combined (P =.026). Procedure-related mortality declined with institutional experience, from 4% among the first 100 patients undergoing TE to 1% among the last 105. For strata 0-3, median LOS were 2, 3, 3, and 4 days, respectively. Seventy patients (22.9%) had 75 endoleaks, of which 30 necessitated additional procedures, 17 self-resolved, and 22 were untreated as of March 1, 2001. Five patients with endoleak died of unrelated causes. One late-onset type IA endoleak (26 mo) resulted in the only AAA rupture and death in the follow-up period among the 291 patients who underwent successful transluminal endograft implantation. Actuarial survival rates at 1 year after TE were 90.3% +/- 1.9% for the overall study group and 97.5% +/- 2.5%, 94% +/- 2.5%, 86.9% +/- 3.3%, and 81.3% +/- 7.7% for risk strata 0-3, respectively. At 5 years, overall actuarial survival was 69.6% +/- 6.1%. Thirty-eight late deaths were attributable to post-TE AAA rupture (n = 1), AAA rupture late after failed TE with no further treatment (n = 1), other cardiovascular disorders (n = 7), cancer (n = 15), other causes (n = 10), and unknown causes (n = 4). Late deaths occurred in risk strata 0-3 at the following rates: two of 40 (5%), 10 of 118 (8.5%), 16 of 116 (13.8%), and 10 of 31 (32.3%), respectively (stratum 0 vs stratum 3, P =.0017; stratum 1 vs stratum 3, P =.003). CONCLUSIONS: TE is safe and confers durable protection against AAA rupture in treated populations. Still, protection is not absolute in patients with endoleaks, because late AAA enlargement and even rupture can occur. Given current knowledge, technology, and practice, careful patient selection and close surveillance of patients after implantation of transluminal endografts is essential.
PURPOSE: Women appear to have a greater risk of death than men after open surgery for abdominal aortic aneurysm (AAA). The aim of this study is to compare outcomes after endovascular AAA repair in men and women. MATERIALS AND METHODS: From March 1994 to November 2000, 305 patients (281 men and 24 women) underwent AAA repair with use of endovascular techniques. Outcomes measured included perioperative mortality, percentage of procedures aborted or converted to open abdominal AAA repair, deployment success rate, angiographic success rate, major complication rate, and percentage of patients with endoleaks. RESULTS: Patients of both genders were comparable with respect to mean age (74.4 in men vs 75.9 in women; NS). According to the Society for Vascular Surgery/International Society of Cardiovascular Surgery risk stratification method, men and women were also comparable in age risk score (0.60 vs 0.67; NS), pulmonary risk score (0.50 vs 0.83; NS), and renal risk score (0.28 vs 0.17; NS). However, the cardiac risk score was higher in men (1.31 vs 0.80; P <.05) and maximum AAA diameter was greater in men (57.0 mm vs 52.1 mm; P <.01). Eight perioperative deaths (2.6%) occurred (2.8% of men, 0% of women; NS). Proportionately more procedures were aborted in women than men: four (16.7%) versus six (2.1%; P <.01). Conversion to open repair occurred in four men (1.4%) and no women (NS). Deployment success was achieved in 96.4% of men and 83.3% of women (P <.01). Angiographic success was achieved in 84.1% of men and 80% of women (NS). Of 46 major complications, 42 (14.9%) occurred in 281 men and four (16.7%) occurred in 24 women (NS). Sixty-seven patients had endoleaks: 60 were men (22.1%) and seven were women (35%; NS). CONCLUSIONS: There was no difference between men and women with respect to perioperative mortality and major complication rates. These findings indicate that being a woman does not adversely influence the outcome of endovascular AAA repair. However, women had a higher rate of aborted procedures. Precise preoperative evaluation may help reduce this problem in women.
The endovascular repair of abdominal aortic aneurysms is gaining widespread acceptance worldwide. It relies on the exclusion of the aneurysm sac from arterial pressure/blood flow to reduce the pressure within it and therefore prevent the fatal complication of rupture. The presence of an endoleak is clear evidence that communication between the native circulation and the aneurysm sac persists. Unfortunately, direct measurement of the sac pressure is not a practical or safe method for routine detection or follow-up of endoleaks. Therefore, a fast, safe, sensitive, and reproducible method must be available. Although many imaging modalities have been and continue to be investigated, computed tomography angiography remains the gold standard. This article describes the various modalities used for the detection of endoleaks and discusses their imaging characteristics.
Since the Food and Drug Administration approved the Ancure (Guidant Corp, Menlo Park, CA) and AneuRx (Medtronic Corp, Minneapolis, MN) abdominal aortic aneurysm stent-grafts, there has been a tremendous increase in the number of stent-graft implantations, both in the United States and worldwide. Successful stent-graft deployment requires complex interventional skills and accurate preprocedure planning. Even the most skilled operator may experience intraoperative difficulties during graft deployment. There are intraprocedural complications that are common to all stent-grafts, as well as specific complications that are unique to the particular stent-graft being implanted. The first step to managing an intraprocedural complication is to be able to quickly recognize that a deployment difficulty has occurred. The interventionalist must then be ready to use common troubleshooting techniques to rectify or avoid complications of stent-graft delivery.
The purpose of this article is to help the reader understand the importance of imaging findings and treatment strategies for type I and III endoleaks. Although the appearance of these leaks on computed tomography can be somewhat unremarkable and similar in appearance to type II endoleaks, it is critically important for the treating physician to make the correct diagnosis, as these endoleak types signify an incompletely treated aneurysm. Once the diagnosis of a type I or III endoleak is made, the next step in treatment is to identify the cause of the endoleak. Incomplete initial graft expansion, further arterial dilation, endograft migration, component separation, and tears within the graft fabric are all possible causes of type I and III endoleaks. A combination of computed tomography, plain film radiography, and diagnostic angiography may be necessary to make the diagnosis and identify the underlying cause of the complication. Once all of these factors have been determined, a decision has to be made of whether the endoleak can be treated through additional endovascular means or if endovascular therapy has failed for the patient, making open surgical revision necessary to treat the aneurysm. Illustrative cases of all endoleak types and their treatments are the focus of this article.
As a result of endovascular repair of abdominal aortic aneurysms and the necessary associated adjunctive procedures, postoperative buttock claudication and limb thrombosis are complications that every physician who implants stent-grafts should be able to recognize and treat. Whereas the presenting complaints of these complications can be quite obvious, the treatment of them may be not so simple. Studies have shown that 28% of patients who underwent embolization of one or both hypogastric arteries develop buttock claudication. Yet 78% of these affected patients spontaneously resolve their symptoms. Strategies to both minimize and successfully treat this complication are obviously of the utmost importance. Likewise, limb thrombosis can be easy to recognize, but treatment strategies and methods to limit this complication can be quite complex and remain somewhat controversial. One center was able to reduce their limb thrombosis rate from 17% to 0% through the use of intravascular ultrasound and aggressive adjunctive stenting. The purpose of this article is to first review the data concerning these complications and then to discuss treatment strategies that are designed to minimize and treat the actual complication.
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OBJECTIVE: The potential of general practitioners (GPs) to reduce the prevalence of alcohol-related problems via alcohol intervention contrasts sharply with actual practice. One explanation for GPs' limited involvement in alcohol intervention is that they have had inadequate training or continuing medical education (CME) on alcohol-related issues. This study examined GPs' experience of alcohol-related CME and its possible relationship with attitudes and practice behavior regarding alcohol-related problems. METHOD: A questionnaire-based survey was returned by 2,139 GPs from 13 countries across Western and Eastern Europe. North America and Australasia. Diagnostic and management skills were assessed by responses to standardized case vignettes. RESULTS: The survey response rate was 54%. Approximately one third of GPs (32%) reported receiving no alcohol-related CME, while 8% could not remember whether or not they had received any such training or education. Of the remaining GPs (n = 1,217), 23% reported less than 4 hours (low levels) and 37% reported 4 or more hours (high levels) of alcohol-related CME. GPs who reported higher levels of alcohol-related CME were more likely to obtain information about alcohol, were more prepared to counsel problem drinkers and managed more patients for alcohol issues than did colleagues reporting lower levels of CME. Those with greater CME experience were also more confident about their ability to alleviate alcohol-related problems and reported more appropriate management strategies than did GPs with less CME experience. CONCLUSIONS: Greater exposure to alcohol-related CME appears to result in better diagnosis and more appropriate management of alcohol-related problems by GPs. Whether this is directly due to the CME itself or because GPs with greater interest in alcohol issues seek out such experience cannot be ascertained from the current study and requires further investigation.
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OBJECTIVES: To assess the preliminary clinical results of implantation of dual chamber pacemaker defibrillator and to evaluate the safety and effectiveness of placement of endocardial leads in the axillary vein. METHODS: Seven patients with ventricular tachycardia and/or ventricular fibrillation (VT/VF), associated with bradyanhythmia received implantation of a dual chamber pacemaker defibrillator, including 5 patients with coronary artery disease and 2 patients with dilated cardiomyopathy. The atrial and ventricular leads were introduced via the axillary vein under venographic guidance. RESULTS: Dual chamber pacemaker defibrillators were successfully implanted in the left chest subcutaneous pocket in 5 patients and the left pectoral muscular pocket in 2 patients. All the VT/VF occurring either inducibly during the procedure or spontaneuously during follow-up were detected promptly and treated successfully. Both the pacing and sensing functions were satisfactory. The endocardial leads required were successfully introduced via the axillary vein without major complications. CONCLUSIONS: Dual chamber pacemaker defibrillators can provide reliable therapy for VT/VF and the dual chamber pacing function. Placement of endocardial leads via the axillary vein under venographic guidance is safe and effective.
The role of constitutive nitric oxide (NO) release in enteric neural pathways regulating ion transport was examined in guinea pig distal colon, in vitro and ex vivo. In in vitro studies, 43% of colonic preparations exhibited oscillations in baseline short-circuit current (Isc), which were reduced by tetrodotoxin (TTX). The NO chelator, hemoglobin (Hb), and neuronal NO synthase inhibitor, 7-nitroindazole (7-NI), significantly increased the baseline Isc in these tissues, which was reduced by TTX. In tissues without oscillations in baseline Isc, Hb reduced the Isc, while 7-NI had little effect. In all tissues, electrical field stimulation (EFS; 15 V/10 Hz) caused a biphasic increase in the Isc which was enhanced by both Hb and 7-NI. In the ex vivo studies, basal release of nitric oxide was significantly lower in colonic segments isolated from guinea pigs administered N omega-nitro-L-arginine methyl ester (L-NAME) i.p. compared to control tissues. Moreover, carbachol, caused a 10-fold increase in NO release in control tissues, but had no effect in tissues isolated from the L-NAME group. L-NAME increased tissue conductance and EFS-induced changes in Isc, which were reversed by L-arginine. However, carbachol-induced ion secretion was unaltered in the L-NAME group compared to control animals. The results suggest that, in guinea pig colon, constitutive enteric NO release tonically suppresses submucous neural activity and it is involved in the maintenance of basal epithelial chloride secretion and mucosal permeability. Hence, constitutive NO promotes a delicate balance between pro-absorptive and pro-secretory processes in guinea pig colon.
The authors present a patient with a specific ECG pattern and a history of syncope and malignant ventricular arrhythmias. Patients without demonstrable structural heart disease and an ECG pattern of RBBB and ST segment elevation in leads V1 through V3 are at risk for sudden cardiac death. They demonstrate the role of cardiac electrophysiology study including programmed ventricular stimulation and pharmacological testing in evaluation of patients with possible Brugada syndrome. The authors emphasize the role of implantable cardioverter defibrillator (ICD) therapy in treatment of patients with Brugada syndrome.
AIM: To quantify the prevalence and demography of at-risk and problematic drinkers in the population attending a random selection of general practices and to compare this with similar studies. METHOD: A study examining the uptake and utilisation of the "DRINKLESS" package to 369 New Zealand general practitioners was conducted during 1995/6. The "DRINKLESS" package was developed with the World Health Organisation collaborative study for brief intervention for at-risk alcohol consumption. The package uses the Alcohol Use Disorders Identification Test (AUDIT). There were 15,670 completed AUDIT questionnaires collected during the study. These were analysed to ascertain the prevalence and demography of at-risk and problematic drinkers attending general practitioners. RESULTS: There were 16% of patients identified as having either "risky drinking" or "problematic or dependent drinking". This pattern varied according to the occupation, age and gender of patients. CONCLUSIONS: The data confirm that large numbers of patients presenting to general practitioners experience alcohol problems of varying degrees. This study also suggests that the AUDIT will have satisfactory detection rates in a primary care setting.
PURPOSE: To assess the feasibility and efficacy of reteplase in transcatheter arterial thrombolysis for lower extremity occlusive disease. MATERIALS AND METHODS: Fifteen consecutive patients with acute lower extremity ischemia due to occlusive disease were treated by means of catheter-directed thrombolysis with reteplase. Following diagnostic angiography, thrombolysis was started either from an antegrade puncture site in cases of femoropopliteal occlusions, or from the contralateral groin in cases of thrombosis of the iliac artery, common femoral artery, or infrainguinal bypass grafts. Reteplase was infused at a rate of either 0.5 U/h (six patients) or 1.0 U/h (nine patients). RESULTS: Complete thrombolysis was achieved in all of the nine (100%) patients in the 1.0 U/h group and in four of six (66%) patients in the 0.5 U/h group for a combined success rate of 13 of 15 (87%). Clinical success was achieved in 11 of 15 patients overall (73%). Major bleeding complications occurred in none of the 9 patients in the 1.0 U/h group and in one (16%) of the six patients in the 0.5 U/h group for an overall rate of 6%. CONCLUSIONS: Reteplase shows promise as an alternative to urokinase in the treatment of lower extremity ischemia due to arterial occlusive disease.