Survival of patients with diabetes and multivessel coronary artery disease after surgical or percutaneous coronary revascularization: results of a large regional prospective study. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: We sought to assess survival among patients with diabetes and multivessel coronary artery disease (MVD) after percutaneous coronary intervention (PCI) and after coronary artery bypass grafting surgery (CABG). BACKGROUND: The Bypass Angioplasty Revascularization Investigation (BARI) demonstrated that diabetics with MVD survive longer after initial CABG than after initial PCI. Other randomized trials or observational databases have not conclusively reproduced this result. METHODS: A large, regional database was linked to the National Death Index to assess five-year mortality. Of 7,159 consecutive patients with diabetes who underwent coronary revascularization in northern New England during 1992 to 1996, 2,766 (38.6%) were similar to those randomized in the BARI trial. Percutaneous coronary intervention was the initial revascularization strategy in 736 patients and CABG in 2,030. Cox proportional hazards regression was used to calculate risk-adjusted hazard ratios (HR) and 95% confidence intervals (CI 95%). RESULTS: Patients who underwent PCI were younger, had higher ejection fractions and less extensive coronary disease. After adjusting for differences in baseline clinical characteristics, patients with diabetes treated with PCI had significantly greater mortality relative to those undergoing CABG (HR = 1.49; CI 95%: 1.02 to 2.17; p = 0.037). Mortality risk tended to increase more among 1,251 patients with 3VD (HR = 2.02; CI 95%: 1.04 to 3.91; p = 0.038) than among 1,515 patients with 2VD (HR = 1.33; CI 95%: 0.84 to 2.1; p = 0.21). CONCLUSIONS: In this analysis of a large regional contemporary database of patients with diabetes selected to be similar to those enrolled in the BARI trial, five-year mortality was significantly increased after initial PCI. This supports the BARI conclusion on initial revascularization of patients with diabetes and MVD.

Safety and efficacy of percutaneous coronary interventions performed immediately after diagnostic catheterization in northern new england and comparison with similar procedures performed later.

"Ad hoc" percutaneous coronary interventions (PCIs)-those performed immediately after diagnostic catheterization-have been reported in earlier studies to be safe with a suggestion of higher risk in certain subgroups. Despite increasing use of this strategy, no data are available in recent years with new device technology. We studied use of an ad hoc strategy in a large regional population to determine its use and outcomes compared with staged procedures. A database from the 6 centers performing PCIs in northern New England and 1 center in Massachusetts was analyzed. During 1997, excluding only patients requiring emergency procedures or those with a prior PCI, 4,136 PCIs were performed, 1,748 (42.3%) of these being ad hoc procedures. Patients having ad hoc procedures were less likely to have peripheral vascular disease, renal failure, prior myocardial infarction, or coronary artery bypass surgery, congestive heart failure, or poor left ventricular function, and more likely to have received preprocedural intravenous heparin or nitroglycerin or to have required an urgent procedure. Narrowings treated during ad hoc procedures were less frequently types B and C or in saphenous vein grafts. Adjusted rates of clinical success were not different between ad hoc and non-ad hoc procedures (93.7% vs 93.6%); there was no difference in the incidence of death (0.6% vs 0.5%), emergency (0. 9% vs 0.8%) or any (1.4% vs 0.8%) coronary artery bypass surgery, or myocardial infarction (2.6% vs 2.0%). As currently practiced in our region, ad hoc intervention is used selectively with outcomes similar for ad hoc and non-ad hoc procedures.

The relationship between operator volume and outcomes after percutaneous coronary interventions in high volume hospitals in 1994-1996: the northern New England experience. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: The purpose of this study was to examine the relationship between annual operator volume and outcomes of percutaneous coronary interventions (PCIs) using contemporaneous data. BACKGROUND: The 1997 American College of Cardiology (ACC)/American Heart Association task force based their recommendation that interventionists perform > or = 75 procedures per year to maintain competency in PCI on data collected largely in the early 1990s. The practice of interventional cardiology has since changed with the availability of new devices and drugs. METHODS: Data were collected from 1994 through 1996 on 15,080 PCIs performed during 14,498 hospitalizations by 47 interventional cardiologists practicing at the five high volume (>600 procedures per hospital per year) hospitals in northern New England and one Massachusetts-based institution that support these procedures. Operators were categorized into terciles based on their annualized volume of procedures. Multivariate regression analysis was used to control for case-mix. In-hospital outcomes included death, emergency coronary artery bypass graft surgery (eCABG), non-emergency CABG (non-eCABG), myocardial infarction (MI), death and clinical success (> or = 1 attempted lesion dilated to < 50% residual stenosis and no death, CABG or MI). RESULTS: Average annual procedure rates varied across terciles from low = 68, middle = 115 and high = 209. After adjusting for case-mix, clinical success rates were comparable across terciles (low, middle and high terciles: 90.9%, 88.8% and 90.7%, Ptrend = 0.237), as were all the adverse outcomes including death (low-risk patients = 0.45%, 0.41%, 0.71%, Ptrend = 0.086; high-risk patients = 5.68%, 5.99%, 7.23%, Ptrend = 0.324), eCABG (1.74%, 2.05%, 1.75%, Ptrend = 0.733) and MI (2.57%, 1.90%, 1.86%, Ptrend = 0.065). CONCLUSIONS: Using current data, there is no significant relationship between operator volumes averaging > or = 68 per year and outcomes at high volume hospitals. Future efforts should be directed at determining the generalizability of these results.

Changing outcomes in percutaneous coronary interventions: a study of 34,752 procedures in northern New England, 1990 to 1997. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: We sought to evaluate the changing outcomes of percutaneous coronary interventions (PCIs) in recent years. BACKGROUND: The field of interventional cardiology has seen considerable growth in recent years, both in the number of patients undergoing procedures and in the development of new technology. In view of recent changes, we evaluated the experience of a large, regional registry of PCIs and outcomes over time. METHODS: Data were collected from 1990 to 1997 on 34,752 consecutive PCIs performed at all hospitals in Maine (two), New Hampshire (two) and Vermont (one) supporting these procedures, and one hospital in Massachusetts. Univariate and multivariate regression analyses were used to control for case mix. Clinical success was defined as at least one lesion dilated to <50% residual stenosis and no adverse outcomes. In-hospital adverse outcomes included coronary artery bypass graft surgery (CABG), myocardial infarction and mortality. RESULTS: Over time, the population undergoing PCIs tended to be older with increasing comorbidity. After adjustment for case mix, clinical success continued to improve from a low of 88.2% in earlier years to a peak of 91.9% in recent years (p trend <0.001). The rate of emergency CABG after PCI fell in recent years from a peak of 2.3% to 1.3% (p trend <0.001). Mortality rates decreased slightly from 1.2% to 1.1% (p trend 0.007). CONCLUSIONS: There has been a significant improvement in clinical outcomes for patients undergoing PCIs in northern New England, including a significant decline in the need for emergency CABG.

Multivariate prediction of in-hospital mortality after percutaneous coronary interventions in 1994-1996. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: Using recent data, we sought to identify risk factors associated with in-hospital mortality among patients undergoing percutaneous coronary interventions. BACKGROUND: The ability to accurately predict the risk of an adverse outcome is important in clinical decision making and for risk adjustment when assessing quality of care. Most clinical prediction rules for percutaneous coronary intervention (PCI) were developed using data collected before the broader use of new interventional devices. METHODS: Data were collected on 15,331 consecutive hospital admissions by six clinical centers. Logistic regression analysis was used to predict the risk of in-hospital mortality. RESULTS: Variables associated with an increased risk of in-hospital mortality included older age, congestive heart failure, peripheral or cerebrovascular disease, increased creatinine levels, lowered ejection fraction, treatment of cardiogenic shock, treatment of an acute myocardial infarction, urgent priority, emergent priority, preprocedure insertion of an intraaortic balloon pump and PCI of a type C lesion. The receiver operating characteristic area for the predicted probability of death was 0.88, indicating a good ability to discriminate. The rule was well calibrated, predicting accurately at all levels of risk. Bootstrapping demonstrated that the estimate was stable and performed well among different patient subsets. CONCLUSIONS: In the current era of interventional cardiology, accurate calculation of the risk of in-hospital mortality after a percutaneous coronary intervention is feasible and may be useful for patient counseling and for quality improvement purposes.

Cause of in-hospital death in 12,232 consecutive patients undergoing percutaneous transluminal coronary angioplasty. The Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Some deaths after percutaneous coronary angioplasty (PTCA) occur in high-risk situations (eg, shock), whereas others are unexpected and related to procedural complications. To better describe the epidemiologic causes of death after PTCA, we undertook a systematic review of all in-hospital PTCA deaths in Northern New England from 1990 to 1993. METHODS: The medical records of 121 patients who died during their acute hospitalization for PTCA were reviewed with a standardized data extraction tool to determine a mode of death (eg, low output failure, arrhythmia, respiratory failure) and a circumstance of death (eg, death attributable to a procedural complication, preexisting acute cardiac disease). Any death not classified as a procedural complication was reviewed by a committee and the circumstance of death assigned by a majority rule. RESULTS: Low-output failure was the most common mode of death occurring in 80 (66.1%) of 121 patients. Other modes of death included ventricular arrhythmias (10.7%), stroke (4.1%), preexisting renal failure (4.1%), bleeding (2.5%), ventricular rupture (2.5%), respiratory failure (2.5%), pulmonary embolism (1.7%), and infection (1.7%). The circumstance of death was a procedural complication in 65 patients (53.7%) and a preexisting acute cardiac condition in 41 patients (33.9%). Women were more likely to die of a procedural complication than were men. CONCLUSION: Procedural complications account for half of all post-PTCA deaths and are a particular problem for women. Other deaths are more directly related to patient acuity or noncardiac, comorbid conditions. Understanding why women face an increased risk of procedural complications may lead to improved outcomes for all patients.

Percutaneous transluminal coronary angioplasty in the elderly: epidemiology, clinical risk factors, and in-hospital outcomes. The Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: To explore the relation between older age and clinical presentation, procedural success, and in-hospital outcomes among a large unselected population undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Although more elderly patients are receiving PTCA, studies of post-PTCA outcomes among the elderly have been limited by small numbers and exclusive selection criteria. METHODS: Data were collected as a part of a prospective registry of all percutaneous coronary interventions performed in Maine, New Hampshire, and from 1 institution in Massachusetts between October 1989 and December 1993. Comparisons across 4 age groups, (<60, 60 to 69, 70 to 79, and 80 years and above) were performed using chi-square tests, the Mantel-Haenzsel test for trend, and logistic regression. RESULTS: Twelve thousand one hundred seventy-two hospitalizations for PTCA were performed with 507 of them (4%) in persons at least 80 years old. Octogenarians were more likely to be women, have multivessel disease, high-grade stenoses, and complex lesions but were less likely to have hypercholesterolemia, a history of smoking, or have undergone a previous PTCA. In the elderly, PTCAs were more often performed urgently and for unstable syndromes compared with younger age groups. Advancing age is strongly associated with in-hospital death, and among the oldest old with an increased risk of postprocedural myocardial infarction. Despite differing presentation and procedural priority, angiographic success and subsequent bypass surgery did not vary by age. CONCLUSIONS: With the increasing age of the population at large as well as that segment at risk for cardiac revascularization, information about age-associated risks of the procedure, especially the substantially higher risk of death in octogenarians, will be critical for both physicians and patients considering PTCA.

Renal response to hemodilution with albumin or crosslinked bovine hemoglobin: role of nitric oxide.

The decreased hematocrit that occurs with hemodilution leads to a decrease in peripheral resistance while venous return and cardiac output increase. We determined systemic and renal responses to hemodilution with a solution of albumin or a crosslinked hemoglobin-based oxygen carrier (XLHb) and the effect of inhibition of NO synthesis on the responses to albumin. Clearance experiments were done on anesthetized rats to determine mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and sodium excretion before and after isovolemic exchange transfusion (2 ml per 100 gm body weight) with either (1) 5% albumin (n = 5), (2) 5% albumin plus N omega-nitro-L-arginine methyl ester (L-NAME, 3.5 mg/kg; n = 6), or (3) 6% XLHb (n = 7) and after administration of L-NAME alone (n = 4). Hematocrit decreased similarly in all exchange groups (from 42 +/- 1.0 to 29 +/- 1.3). MAP decreased with albumin exchange, increased with L-NAME, and remained unchanged with albumin+L-NAME or XLHb. GFR, ERPF, and renal blood flow increased while filtration fraction and renal resistance decreased with albumin exchange; responses were the opposite with L-NAME, and with albumin+L-NAME and XLHb these parameters remained approximately the same as control values. Red cell delivery decreased with L-NAME, albumin+L-NAME, and XLHb but remained at control levels with albumin. In conclusion, renal effects of decreased hematocrit can be offset by decreased NO availability. The similarity of results with XLHb and albumin+L-NAME is consistent with NO scavenging by hemoglobin. Increased renal vascular tone with XLHb limits oxygen delivery.

Operator volume and outcomes in 12,998 percutaneous coronary interventions. Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: We sought to determine whether there is a relation between operator volume and outcomes for percutaneous coronary interventions (PCIs). BACKGROUND: A 1993 American College of Cardiology/American Heart Association task force stated that cardiologists should perform > or = 75 procedures/year to maintain competency in PCIs; however, there were limited data available to support this statement. METHODS: Data were collected from 1990 through 1993 on 12,988 PCIs (12,118 consecutive hospital admissions) performed by 31 cardiologists at two hospitals in New Hampshire and two in Maine and one hospital in Massachusetts supporting these procedures. Operators were categorized into terciles based on annualized volume of procedures. Univariate and multivariate regression analyses were used to control for case-mix. Successful outcomes included angiographic success (all lesions attempted dilated to < 50% residual stenosis) and clinical success (at least one lesion dilated to < 50% residual stenosis and no adverse outcomes). In-hospital adverse outcomes included coronary artery bypass graft surgery (CABG), myocardial infarction (MI) and death. RESULTS: After adjustment for case-mix, higher angiographic (low, middle and high terciles: 84.7%, 86.1% and 90.3%, p-trend 0.006) and clinical success rates (85.8%, 88.0% and 90.7%, p-trend 0.025), with fewer referrals to CABG (4.54%, 3.75% and 2.49%, p-trend <0.001), were seen as operator volume increased. There was a trend toward higher MI rates for high volume operators (2.00%, 1.98% and 2.57%, p-trend 0.06); all terciles had similar in-hospital mortality rates (1.09%, 0.96% and 1.05%, p-trend 0.8). CONCLUSIONS: There is a significant relation between operator volume and outcomes in PCIs. Efforts should be directed toward understanding why high volume operators are more successful and encounter fewer adverse outcomes.

Results of directional coronary atherectomy in Northern New England. Northern New England Cardiovascular Disease Study Group.

The role of directional coronary atherectomy (DCA) in interventional cardiology remains uncertain. We report the Northern New England regional experience with DCA from 1991 to 1994. Data were collected on 11,178 patients having had an intervention on a single lesion in a single vessel (798 DCAs; 10,380 percutaneous transluminal angioplasties [PTCA]). The use of DCA increased from 1.8% of interventions in 1991 to 10% in 1994. Compared with PTCA, DCA patients were younger, more often men, had more 1-vessel disease and more coronary artery bypass surgery (CABG). DCA was more often used in the left anterior descending artery, in vein grafts, for restenoses, for subtotal occlusions, and with type A lesions. Angiographic success (96.7%) and clinical success (93%) were good. Adverse events were rare: mortality 0.9%, emergent CABG 2.2%, nonfatal myocardial infarction 2.8%. After adjusting for case-mix, there was no difference between DCA and PTCA for in-hospital mortality (odds ratio [OR] = 1.03, 95% confidence interval [CI] 0.44 to 2.43, p = 0.95) or need for emergent CABG (OR = 1.27, 95% CI 0.77 to 2.10, p = 0.34). Atherectomy patients were more likely to have a nonfatal myocardial infarction (OR = 2.0, 95% CI 1.26 to 3.20, p <0.01), to sustain an injury to the femoral or brachial artery (OR = 2.89, 95% CI 1.52 to 5.51, p <0.01), and to have a clinically successful procedure (OR = 1.37, 95% CI 1.01 to 1.88, p = 0.05). Our results support the relative safety and effectiveness of DCA as its use disseminated into the region.

The relationship between the supply of cardiac catheterization laboratories, cardiologists and the use of invasive cardiac procedures in northern New England.

OBJECTIVES: Utilization rates of coronary angiography and cardiac revascularization have been found to vary between areas. This study addresses the relationship between resource supply and procedure rates. METHODS: We compared the association of per capita catheterization laboratories, per capita cardiologists and multi-provider markets (where more than one hospital offers coronary angiography services) with the utilization rates for angiography and cardiac revascularization in northern New England, USA. Administrative data were used to capture invasive cardiac procedures. Small area analyses were used to create coronary angiography service areas. Linear regression methods were used to measure associations between the resource supply and utilization rates. RESULTS: Variation in the use of invasive cardiac procedures was strongly associated with the population-based availability of catheterization facilities and multi-provider markets and unrelated to cardiologist supply or need (as reflected in the hospitalization rates for myocardial infarction). In the multivariate model, an increase of 1 catheterization laboratory per 100,000 population was associated with an increase in the angiography rate of 1.62 per 1000 population; those service areas with multi-provider markets were associated with an additional increase in the angiography rate of 1.27 per 1000 population (R2 = 0.84, P = 0.0006). There was a moderately strong relationship between the catheterization laboratories per capita and the revascularization rates (R2 = 0.43, P = 0.029). Angiography rates were highly associated with cardiac revascularization rates: an increase in the angiography rate of 1 per 1000 population was associated with a 0.46 per 1000 increase in the cardiac revascularization rate (R2 = 0.85, P = 0.0001). CONCLUSIONS: Our work suggests that current efforts to address variation in cardiac procedures through activities such as appropriateness criteria, guidelines and utilization review are misdirected and should be redirected towards capacity, in this case the supply of catheterization facilities.

Differences in outcomes between women and men associated with percutaneous transluminal coronary angioplasty. A regional prospective study of 13,061 procedures. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: A prospective study of patients undergoing percutaneous transluminal coronary angioplasty was conducted to examine differences in mortality and nonfatal outcomes by sex. Data were collected on 12,232 patients representing 13,061 trips to the catheterization laboratory for percutaneous transluminal coronary angioplasty (PTCA) of 17,096 lesions between 1989 and 1993. Differences in patient characteristics, comorbidities, severity of illness, and treatments were examined and crude and adjusted odds ratios (ORs) for women versus men reported. METHODS AND RESULTS: Rates of success, fatal and nonfatal outcomes, ORs, and 95% Cls were calculated. Clinical success for women (88.8%) and men (87.9%) was good and comparable. Mortality rates for women (1.64%) and men (0.7%) differed, with an OR (women versus men) of 2.34 (95% CI, 1.64, 3.35). Nonfatal adverse outcomes rates (coronary artery bypass grafting and myocardial infarction) for women (5.29%) and for men (4.29%) were of borderline significance, with an OR of 1.19 (95% CI, 1.00, 1.41). Women were older, were more likely to be hypertensive and diabetic, and had more urgent and emergent procedures. For mortality, the adjusted OR (women versus men) was 1.64 (95% CI, 1.09, 2.47), and for nonfatal adverse outcomes, the OR was 1.14 (95% CI, 0.95, 1.36). CONCLUSIONS: Although the success rate of PTCA for men and women is comparable, women are at higher risk for adverse outcomes. For nonfatal events, the excess risk-is attributable to differences in case mix. For death, the risk remains elevated even after adjusting for case mix.

Production and characteristics of an infusible oxygen-carrying fluid based on hemoglobin intramolecularly cross-linked with sebacic acid.

Research on red cell substitutes requires the availability of oxygen-carrying fluids for physiologic experiments. This article describes the procedure for in-house production of such a fluid. It contains a hemoglobin-based oxygen carrier obtained by reacting human hemoglobin with bis-(3,5-dibromosalicyl) sebacate. This reagent produces intramolecular cross-links between the beta 82 lysines and between the alpha 99 lysines, respectively. The oxygen half-saturation pressure (P50) of the fluid is near 34 mm Hg at 37 degrees C, with a Hill's parameter of n = 2.2. The half-time of intravascular retention is near 3.0 hours in the rat and 6.5 hours in the cat. Spectrophotometric analyses of arterial and venous plasma from an infused rat reveal an efficient oxygen delivery to the tissues by the oxygen carrier. Therefore, this new cross-linked human hemoglobin can be produced in quantities sufficient for in vivo evaluation and with an oxygen affinity and cooperativity adequate for oxygen unloading in plasma.

Use of a solid-phase photoaffinity reagent to label a steroid binding site: application to the delta 5-3-ketosteroid isomerase of Pseudomonas testosteroni.

In order to extend our analysis of the reactions that occur during the active site directed photoinactivation of delta 5-3-ketosteroid isomerase sensitized by unsaturated steroid ketone photoaffinity reagents, the site of covalent attachment has been identified. A solid-phase photoaffinity reagent, delta 6-testosterone-agarose, has been employed for this purpose; this type of reagent, in contrast to solution-phase reagents, facilitated the recovery of a peptide fragment of the isomerase bearing the residue at which covalent attachment had occurred. Amino acid analysis and sequence determination of the peptide provided evidence that the site of attachment was aspartate-38. This result, in combination with the low-resolution crystallographic structure of the enzyme [Westbrook, E. M., Piro, O. E., & Sigler, P. B. (1984) J. Biol. Chem. 259, 9096-9103], suggests that aspartate-38 is located in the vicinity of the bottom of the steroid-binding pit. The potential usefulness of solid-phase photoaffinity reagents in the identification of sites of covalent attachment on target proteins such as hormone receptors is discussed.

Coronary artery surgery and direct coronary artery thrombolysis during acute myocardial infarction.

Twelve patients underwent direct coronary artery streptokinase thrombolysis during acute evolving myocardial infarction. Ten patients had restoration of orthograde pulmonary blood flow. Eight patients had significant myocardial salvage and clinical stabilization. Nine patients had subsequent coronary artery bypass surgery with no major hematological or cardiac complications. Five of these had surgery performed immediately. Two patients with no myocardial salvage after streptokinase had urgent surgery because of other critical coronary lesions. Seven patients with thrombolytic salvage of myocardium underwent urgent coronary artery bypass surgery without incident. The occurrence of two reinfarctions in streptokinase-improved patients waiting for surgery suggests that delay is unwarranted and coronary bypass surgery is needed to insure success.

Photoaffinity modification of delta 5-3-ketosteroid isomerase by light-activatable steroid ketones covalently coupled to agarose beads.

In order to identify the minor site(s) of photoattachment of unsaturated steroid ketones to delta 5-3-ketosteroid isomerase from Pseudomonas testosteroni, we have developed a solid-state photoaffinity labeling technique. Two solid-state reagents, O-carboxymethylagarose-ethylenediamine-succinyl-17 beta-O-19-nortestosterone and O-carboxymethylagarose-ethylenediamine-succinyl-17 beta-O-4,6-androstadien-3-one, have been synthesized. Under anaerobic conditions, isomerase bound to these resins is photoinactivated by UV light (lambda greater than 290 nm) whereas isomerase bound to O-carboxymethylagarose-ethylenediamine-deoxycholate or isomerase in the presence of O-carboxymethylagarose-ethylenediamine-acetate is almost completely stable to irradiation under the same conditions. Photoinactivation under anaerobic condition promoted by the resin-bound steroid ketones results from a reaction at the active site since the competitive inhibitor, sodium cholate, which does not absorb light above 290 nm, provides protection toward photoinactivation. Preliminary analysis of isomerase that has been photolyzed in the presence of O-carboxymethylagarose-ethylenediamine-succinyl-17 beta-O-4,6-androstadiene-3-one has established that the enzyme is converted to at least two different forms. One form binds more tightly to the resin than does the native enzyme. This form can be eluted by a sodium dodecyl sulfate containing buffer. The second form is not eluted by this buffer but can be released from the resin by cleavage of the ester bond linking the steroid to the derivatized agarose. We presume that the latter form is covalently coupled to the resin-linked steroid. In the presence of oxygen, additional nonspecific inactivation reactions occur, but these can be suppressed by the singlet oxygen trap, L-histidine. The application of solid-state photoaffinity reagents to some areas of receptor isolation and characterization is discussed.

Cardiac toxicity of clonidine.

A 22-year-old woman with systemic lupus erythematosus complicated by mild renal insufficiency and severe systemic hypertension inadvertently received an excessive amount of clonidine hydrochloride. In association with a presumed toxic level of clonidine in the serum, the patient developed abnormalities of cardiac conduction, including 2:1 atrioventricular block, complete heart block, 3:2 Wenckebach block, and first-degree atrioventricular block. The transient nature of these abnormalities, with the return of normal conduction upon the cessation of therapy with clonidine, implicates this drug as being capable of producing high-grade atrioventricular block at toxic levels.

Cocking of a poppet-disc prosthesis in the aortic position. A cause of intermittent aortic regurgitation.

Intermittent aortic regurgitation due to cocking is described for the first time after replacement of the aortic valve with a poppet-disc prosthesis. A combination of disc grooving and strut thrombus produced the cocking with resultant aortic regurgitation.

Paradoxical motion of the interventricular septum in a patient with normal right heart hemodynamics.

A 32-year-old man with paradoxical motion of the interventricular septum at the level of the chordae tendineae and with normal right heart hemodynamics is presented. It appears that, in absence of severe left ventricular dysfunction or intraventricular conduction defect, paradoxical septal motion is not entirely specific for right ventricular volume overload and may represent a rare normal variant.