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Biomedical subjects

S S Khan

Publications and source records attributed to S S Khan.

At least 19 recordsLinked to original sources

Reconstitution of mammalian pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes: analysis of protein X involvement and interaction of homologous and heterologous dihydrolipoamide dehydrogenases.

Optimal conditions for rapid and efficient reconstitution of pyruvate dehydrogenase complex (PDC) activity are demonstrated by using an improved method for the dissociation of the multienzyme complex into its constituent E1 (substrate-specific 2-oxoacid decarboxylase) and E3 (dihydrolipoamide dehydrogenase) components and isolated E2/X (where E2 is dihydrolipoamide acyltransferase) core assembly. Selective cleavage of the protein X component of the purified E2/X core with the proteinase arg C decreases the activity of the reconstituted complex to residual levels (i.e. 8-12%); however, significant recovery of reconstitution is achieved on addition of a large excess (i.e. 50-fold) of parent E3. N-terminal sequence analysis of the truncated 35,000-M(r) protein X fragment locates the site of cleavage by arg C at the extreme N-terminal boundary of a putative E3-binding domain and corresponds to the release of a 15,000-M(r) N-terminal fragment comprising both the lipoyl and linker sequences. In native PDC this region of protein X is shown to be partly protected from proteolytic attack by the presence of E3. Recovery of complex activity in the presence of excess E3 after arg C treatment is thought to result from low-affinity interactions with the partly disrupted subunit-binding domain on X and/or the intact analogous subunit binding domain on E2. Contrasting recoveries for arg C-modified E2/X/E1 core, and untreated E2/E1 core of the 2-oxoglutarate dehydrogenase complex, reconstituted with excess bovine heart E3, pig heart E3 or yeast E3 point to subtle differences in subunit interactions with heterologous E3s and offer an explanation for the inability of previous investigators to achieve restoration of PDC function after selective proteolysis of the protein X component.

Amino Acid Sequence

Adverse 5-year outcome after coronary artery bypass surgery in blacks.

BACKGROUND: Coronary heart disease is the leading cause of death among blacks, but little is known about the late results of coronary artery bypass surgery in this population. It is not known whether differences in preoperative medical characteristics or medical health insurance affect outcome. We studied the effects of medical risk factors on survival outcome after coronary artery bypass surgery in a population of medically insured black and white patients. METHODS: Racial status and outcomes from surgery were determined in 3728 consecutive patients who had coronary artery bypass surgery at the authors' institution from January 1, 1984, to June 30, 1992. Coronary artery bypass surgery (excluding valve replacement) was performed in 115 black and 3113 white patients. RESULTS: Late survival probability was worse for blacks than whites at 1 year (84% vs 92%) and at 5 years (64% vs 82%, P=.001, Wilcoxon test). Most deaths were due to cardiac events in both groups (68% in blacks vs 67% in whites). Blacks had more hypertension (84% vs 54%), diabetes mellitus (36% vs 23%), and more were current smokers (21% vs 14%) (all P<.05, Fisher's exact test). Medical insurance coverage for blacks and whites was as follows: Medicare (60% vs 57%), private (38% vs 42%), and Medi-Cal (2% vs 2%). Operative mortality (30 days) was similar (5.2% for blacks vs 4.1% for whites; P=.48, Fisher's exact test). In a Cox regression model, race predicted long-term survival and persisted as an important risk factor after adjusting for preoperative factors related to patient survival (adjusted hazard ratio, 2.10; 95% confidence interval, 1.43 to 3.07). CONCLUSIONS: In this group of predominantly medically insured patients undergoing coronary artery bypass surgery, the risk of death in blacks at 5 years was twice that of whites.

Black or African American

Postinfarction ventricular septal defect in the elderly: analysis and results.

Fifteen elderly patients (age more than 70 years) underwent surgical repair of postinfarction ventricular septal defects during the years 1980 through 1992. The operative (to discharge or < 30 days) mortality rate was 47%, and the complication rate among survivors was 63%. The probability of survival at 1 year was 47% +/- 13%. Because of the small sample size of our patient population, predictive preoperative risk factors associated with early mortality could not be identified with certainty. However, there is a trend suggesting that high right atrial pressures (p = 0.15) and the need of an intraaortic balloon pump preoperatively (p = 0.12) influence 30-day mortality, as previously described in larger series. Of 5 long-term survivors, 3 are in New York Heart Association functional class I and 2 are in class II. Our experience in this group of patients suggests that in the elderly, a very aggressive approach should be taken in recommending early surgical intervention for postinfarction ventricular septal defect before hemodynamic deterioration ensues and severely compromises chances for survival.

Aged

Ten-year experience of cardiac surgery in patients aged 80 years and over.

Five hundred twenty-eight consecutive patients aged 80 years and over (mean age, 83.1 +/- 2.7 years) underwent cardiac operations with hypothermia (mean, 21.9 degrees +/- 2.2 degrees C), hyperkalemic cardioplegia, and cardiopulmonary bypass in a 10-year period. Fifty-six percent of the patients were male. Preoperatively, 68% of the patients were in New York Heart Association functional class IV, and 31% were in class III. Among them, 303 patients had isolated coronary artery bypass grafting (CABG) (group I), 132 had aortic valve replacement only or combined with CABG (group II), 42 had mitral valve replacement only or combined with CABG (group III), 31 had mitral valve repair and CABG (group IV), and 20 had double-valve procedure only or combined with CABG (group V). The 30-day or in-hospital mortality was 8.3% in group I, 4.5% in group II, 29% in group III, 23% in group IV, and 30% in group V. Total 30-day or in-hospital mortality was 10.6%. One-year and 5-year actuarial survival rates were as follows: group I, 82% and 62%; group II, 85% and 58%; group III, 61% and 37%; group IV, 56% and 19%; and group V, 63% and 15%. Total 1-year and 5-year actuarial survival were 79% and 54%. At follow-up (mean, 2 years), 70% of overall survivors reported that their general health had improved. Our experience demonstrates that for select patients aged 80 years and over with unmanageable cardiac symptoms, CABG and aortic valve replacement groups had better results in improving quality of life as compared with patients having mitral or combined procedures.

Actuarial Analysis

Long-term survival after coronary artery bypass grafting.

The most quoted long-term outcome studies from the coronary artery bypass surgery literature were performed in the 1970s, and these trials--the Coronary Artery Surgery Study, the Veterans Administration Study, and the European Cooperative Study--added significantly to our knowledge of the efficacy of bypass surgery. However, important studies are still being performed and are refining our knowledge of long-term outcomes. This review covers early factors that affect long-term outcome, and recent information concerning particular subgroups of patients undergoing bypass surgery. In addition, new information is becoming available about the relative roles of percutaneous transluminal coronary angioplasty and coronary artery bypass grafting, and these studies are also discussed.

Angioplasty, Balloon, Coronary

The St. Jude valve. Thrombolysis as the first line of therapy for cardiac valve thrombosis.

BACKGROUND: Thrombolytic therapy is a promising alternative to valve replacement in the management of prosthetic valve thrombosis. We sought to determine the short- and long-term results of treating thrombosed St. Jude heart valves with thrombolytic therapy as the primary treatment modality. METHODS AND RESULTS: Between March 1978 and December 1991, 988 patients underwent implantation of St. Jude prosthetic valves at our medical center, and all patients with thrombosed valves were identified prospectively. During this period, 17 patients (13 women; mean age, 66.8 +/- 19.0 years) developed prosthetic valve thrombosis (11 aortic, six mitral). In six patients, Coumadin was stopped in preparation for elective surgery. The clinical presentation was congestive heart failure in 13, syncope and fatigue in two, and a cerebrovascular accident in one; one patient was asymptomatic. The average duration of symptoms was 11.7 +/- 12.0 days (range, 1-45 days). Anticoagulation was subtherapeutic in all but one patient at the time of presentation. Cinefluoroscopy was the primary method used for diagnosis and was also used to follow the response to therapy. Twelve patients were treated medically (10 with thrombolytic therapy and two with heparin), three were treated surgically, and two were diagnosed at autopsy. Of the 12 medically treated patients, 10 had marked improvement in leaflet movement and symptoms within 12 hours. Thus, 10 of 12 patients (83%) had a satisfactory response to medical therapy alone. No medically treated patient died or had a major complication resulting in permanent damage. However, four of the 12 medically treated patients had minor complications, including a transient episode of facial weakness in one patient, hematomas in two, and epistaxis in one. Late rethrombosis recurred in two patients in the medically treated group and was successfully retreated with thrombolytic therapy. At 3 months, all patients were alive and well. CONCLUSIONS: Thrombolytic therapy can be used as the first line of therapy for thrombosed St. Jude valves with a low risk of permanent side effects and excellent chances of success. In most cases, surgery can be reserved for patients who do not respond to thrombolytic therapy.

Adolescent

Action potential alternans and irregular dynamics in quinidine-intoxicated ventricular muscle cells. Implications for ventricular proarrhythmia.

BACKGROUND: Cardiac cells display rate-dependent beat-to-beat variations in action-potential duration (APD), action potential amplitude (APA), and excitability during periodic stimulation. We hypothesized that quinidine causes a marked increase in the variability of APD, APA, and excitability of ventricular cells isolated from quinidine-toxic, arrhythmic ventricles. METHODS AND RESULTS: Action potentials were recorded from right ventricular endocardial tissues (2 x 1 cm, < 2 mm thick) isolated from dogs in which ventricular tachycardia and ventricular fibrillation (VT/VF) were induced with intravenous quinidine (80-100 mg/kg) over a 5-hour period in vivo (n = 7). As the basic cycle length (BCL) of stimulation was progressively shortened, rate-dependent variations in APD and APA occurred. The initial dynamic change was alternans of APD and APA that could be either in or out of phase between two cells. The magnitude of alternans was a function of the BCL and the strength of the stimulation current. At critically short BCLs, irregular APD and APA behavior emerged in the quinidine-intoxicated cells. In control cells (n = 16) isolated from three nontreated dogs, APD and APA remained constant at all BCLs tested (2,000-300 msec). Quinidine increased the slope of the APD restitution curve compared with control. The observed quinidine APD restitution curve was fitted with a biexponential equation, and computer simulation using the fitted restitution curve reproduced the aperiodic APD seen in the quinidine toxic cells during periodic stimulation. Thus, the observed irregular APD behavior was predictable from the restitution curve. CONCLUSIONS: Quinidine toxicity increases the temporal and spatial variability of APD and APA in the ventricle that may promote the initiation of reentrant VT/VF in vivo. The slope of the APD restitution curve provides a method to quantitate inhomogeneities in repolarization time and could be a useful marker for proarrhythmia.

Action Potentials

Assessment of prosthetic valve hemodynamics by Doppler: lessons from in vitro studies of the St. Jude valve.

Although Doppler assessment of native heart valve hemodynamics is quite accurate, assessment of prosthetic mechanical valve hemodynamics presents more potential problems. These problems arise from the unique geometry of prosthetic valves. Two important prosthetic valve phenomena can violate the basic assumptions underlying Doppler calculations: pressure recovery and localized gradients. When pressure recovery is present, Doppler systematically overestimates the actual net catheter gradient across the valve. In contrast, the presence of localized gradients may cause Doppler to measure differing gradients depending on which part of the valve is interrogated. These phenomena can also affect the calculation of prosthetic valve areas using the continuity equation. When assessing prosthetic valves with Doppler echocardiography, it must be remembered that Doppler measures velocity, not pressure gradients and that the echocardiographer must exercise great care when interpreting Doppler velocities as either pressure gradients or in calculating valve areas for prosthetic valves.

Acceleration

Case report: liver adenomatosis presenting as multiple calcified masses.

Liver adenomatosis is a rare condition with only 14 cases reported. It is considered to be a distinct entity from liver adenoma. This is the first case in which calcification has been described. The differential diagnosis of multiple calcified lesions in the liver is discussed, and other features of liver adenomatosis.

Adenoma

Phase plane plot of electrograms as a marker of ventricular electrical instability during acute ischemia: initial experimental results and potential clinical applications.

We used a phase plane plots method (a plot of voltage [V(t)] vs rate of change of voltage [dV/dt]) derived from nonlinear dynamics to transform a sinus rhythm strip into a geometric form. The geometric form thus obtained detects variations in the ECG over time and therefore may aid in identifying patterns of vulnerability to ventricular fibrillation (VF). The trajectories of consecutive ventricular depolarizations and repolarizations of sinus rhythm in dogs that evolve to VF showed characteristic differential band thickening (inhomogeneities) that were absent in the dogs that did not develop VF. This method of analysis can be a useful complementary tool to detect cardiac electrical instability, and with simple hardware, can easily be displayed in real time.

Animals

Doppler assessment of prosthetic valve orifice area. An in vitro study.

BACKGROUND: Although Doppler echocardiography has been shown to be accurate in assessing stenotic orifice areas in native valves, its accuracy in evaluating the prosthetic valve orifice area remains undetermined. METHODS AND RESULTS: Doppler-estimated valve areas were studied for their agreement with catheter-derived Gorlin effective orifice areas and their flow dependence in five sizes (19/20-27 mm) of St. Jude, Medtronic-Hall, and Hancock aortic valves using a pulsatile flow model. Doppler areas were calculated three ways: using the standard continuity equation; using its simplified modification (peak flow/peak velocity); and using the Gorlin equation with Doppler pressure gradients. The results were compared with Gorlin effective orifice areas derived from direct flow and catheter pressure measurements. Excellent correlation between Gorlin effective orifice areas and the three Doppler approaches was found in all three valve types (r = 0.93-0.99, SEE = 0.07-0.11 cm2). In Medtronic-Hall and Hancock valves, there was only slight underestimation by Doppler (mean difference, 0.003-0.25 cm2). In St. Jude valves, however, all three Doppler methods significantly underestimated effective orifice areas derived from direct flow and pressure measurements (mean difference, 0.40-0.57 cm2) with differences as great as 1.6 cm2. In general, the modified continuity equation calculated the largest Doppler areas. When orifice areas were calculated from the valve geometry using the area determined from the inner valve diameter reduced by the projected area of the opened leaflets, Gorlin effective orifice areas were much closer to the geometric orifice areas than Doppler areas (mean difference, 0.40 +/- 0.31 versus 1.04 +/- 0.20 cm2). In St. Jude and Medtronic-Hall valves, areas calculated by either technique did not show a consistent or clinically significant flow dependence. In Hancock valves, however, areas calculated by both the continuity equation and the Gorlin equation decreased significantly (p less than 0.001) with low flow rates. CONCLUSIONS: Doppler echocardiography using either the continuity equation or Gorlin formula allows in vitro calculation of Medtronic-Hall and Hancock effective valve orifice areas but underestimates valve areas in St. Jude valves. This phenomenon is due to localized high velocities in St. Jude valves, which do not reflect the mean velocity distribution across the orifice. Valve areas are flow independent in St. Jude and Medtronic-Hall prostheses but decrease significantly with low flow in Hancock valves, suggesting that bioprosthetic leaflets may not open fully at low flow rates.

Aortic Valve

Cellular mechanisms of differential action potential duration restitution in canine ventricular muscle cells during single versus double premature stimuli.

BACKGROUND: We tested the hypothesis that action potential duration (APD) restitution of normal ventricular muscle cells is different during double premature stimuli (S3) compared with a single premature stimulus (S2). We propose a possible ionic mechanism for such a difference. METHODS AND RESULTS: Action potentials and isometric tension were recorded simultaneously from isolated canine right ventricular trabeculae (2 x 2 x 10 mm) (n = 35). APD and tension restitution curves (APD) and peak tension versus diastolic interval [DI] of S2 and S3 were constructed by the extrastimulus method during pacing at 1,500 msec. The following results were obtained. 1) The APD restitution curve of S2 was different from that of S3. During the restitution of S2, an early biphasic upward hump was present at short DIs. In contrast, a smooth exponential rise was consistently seen during S3 restitution. 2) Peak tension remained significantly (p less than 0.001) lower during the restitution of S2 than during S3 restitution at all DIs tested. 3) The variation of APD during the initial 100 msec of DI was significantly longer during S3 than S2 (22 +/- 5 msec versus 41 +/- 5 msec, p less than 0.001). 4) Caffeine (2 mM, n = 5) and ryanodine (10 microM, n = 5) blocked cyclic variations of tension, presumably by blocking cyclic variations of intracellular calcium ion concentrations ([Ca2+]i), and eliminated the differences in APD restitution between S2 and S3. 5) Nisoldipine at high (5 microM) but not at lower (2 microM, n = 5) concentration eliminated the differences in restitution of both APD and tension between S2 and S3. 6) BAY K 8644 (100 nM, n = 5) had no effect on this difference. CONCLUSIONS: Greater variations of APD occur during the restitution of S3 than during S2 at short DIs. These differences appear to be caused by cyclic variations in tension and thus in [Ca2+]i. Calcium-sensitive outward currents could explain these differences in APD restitution.

Action Potentials

Results of early repair of ventricular septal defect after an acute myocardial infarction.

A 10-year experience with early operation for postinfarction ventricular septal defect is reviewed. Twenty-two patients underwent surgical repair; operative mortality was 36% (< 30 days). The actuarial survival was 64% at 1 month, 59% at 1 year, and 47% at 5 years. Risk factors predictive of operative mortality were diabetes (p = 0.001), elevated preoperative right atrial pressure (p = 0.02), the absence of a preoperative intraaortic balloon pump (p = 0.006), and a short time interval between infarct and operation (p = 0.018). Long-term survival was adversely related to diabetes (p = 0.030), elevated preoperative right atrial pressure (p = 0.005), and, surprisingly, survival was better in patients with a greater extent of coronary artery disease (p = 0.023). There were 14 operative survivors (64%) and 11 long-term survivors (3 months to 10 years, mean 6.0 +/- 3.5 years). Six of eleven survivors were in functional New York Heart Association class I, one was in class II, and four were in class III.

Aged

Interaction of age and preoperative risk factors in predicting operative mortality for coronary bypass surgery.

BACKGROUND: Models for predicting operative mortality for coronary bypass surgery assume that preoperative risk factors affect mortality to the same extent in all patients groups. METHODS AND RESULTS: To determine whether certain preoperative risk factors disproportionately increase operative mortality in the elderly, 663 consecutive elderly patients (age 75 years or older) and 1,464 younger patients (age 65 or younger) undergoing isolated coronary bypass surgery between 1982 and 1990 were studied. Hospital mortality was significantly greater in the elderly patients than in younger patients (7.5% versus 1.8%; relative risk, 4.5). Univariate analysis identified age, prior coronary artery bypass grafting, congestive heart failure, left main disease, New York Heart Association functional class, hypertension, prior myocardial infarction (MI), and preoperative atrial fibrillation as associated with mortality. Multivariate analysis was then used to construct a model to describe the risk of operative mortality in terms of selected risk factors. However, comparison of observed mortality rates with those predicted by the model revealed problems with the model's goodness of fit. Further testing revealed that young patients without prior MI had a mortality rate lower by an order of magnitude than either younger patients with prior MI or elderly patient groups with and without MI. Two separate models were therefore constructed stratifying by the presence of prior MI. This resulted in a significant improvement in the fit of the models to the observed data. CONCLUSIONS: These results suggest that the impact of risk factors on the elderly may be significantly different from the effect of these risk factors on younger patients. Models for predicting outcome after bypass surgery should be tested for potential interactions between age and risk factors.

Adult