Asymmetric analysis reveals novel virus capsid features.

Cryo-electron microscopy and single-particle image analysis are frequently used methods for macromolecular structure determination. Conventional single-particle analysis, however, usually takes advantage of inherent sample symmetries which assist in the calculation of the structure of interest (such as viruses). Many viruses assemble an icosahedral capsid and often icosahedral symmetry is applied during structure determination. Symmetry imposition, however, results in the loss of asymmetric features of the virus. Here, we provide a brief overview of the methods used to investigate non-symmetric capsid features. These include the recently developed focussed classification as well as more conventional methods which simply do not impose any symmetry. Asymmetric single-particle image analysis can reveal novel aspects of virus structure. For example, the VP4 capsid spike of rotavirus is only present at partial occupancy, the bacteriophage MS2 capsid contains a single copy of a maturation protein and some viruses also encode portals or portal-like assemblies for the packaging and/or release of their genome upon infection. Advances in single-particle image reconstruction methods now permit novel discoveries from previous single-particle data sets which are expanding our understanding of fundamental aspects of virus biology such as viral entry and egress.

The effects on ruminal pH and serum haptoglobin after feeding a grain-based supplement to grazing dairy cows as a partial mixed ration or during milking.

Ruminal pH and serum concentrations of haptoglobin (Hp) were measured in order to assess the risk of subacute ruminal acidosis (SARA) in grazing cows offered rolled wheat grain twice daily in the dairy at milking (Control group; n= 64), or as a partial mixed ration (PMR group; n= 64) on a feedpad. Cows were allocated various levels of the supplement (8, 10, 12 or 14 kg dry matter/day). Ruminal pH was measured in 16 rumen-fistulated cows (eight PMR and eight Control group cows), using indwelling pH meters, recording every 10 min for 14 days. Serum Hp was analysed in samples collected from 125 cows. No differences in ruminal pH or serum Hp concentration were found between treatment groups, or levels of feeding. It was concluded that, using ruminal pH patterns and Hp as markers of SARA at the feeding levels used in this study, there were no differences between grazing cows fed the supplement either as grain in the dairy or as a PMR fed on a feedpad.

Syncope secondary to paroxysmal high grade AV block in a heavily trained man.

J.B. is a well-trained male with syncope due to paroxysmal AV nodal heart block who ultimately required a permanent pacemaker despite an initial attempt at cessation of training only. Baseline sinus node function was normal, but AV nodal conduction remained abnormal even after autonomic blockade supporting intrinsic AV nodal dysfunction. This case illustrates that vigorous physical training may unmask previously unrecognized intrinsic dysfunction of AV nodal conduction or, as previously reported for physical training induced sinus node dysfunction, cause AV nodal dysfunction. Simple cessation of training to treat this problem is often recommended but may not be adequate for some patients who remain at risk for recurrent syncope during the deconditioning period.

Prognostic value of a normal exercise echocardiogram.

Follow-up information was obtained from 148 patients who had normal resting and post-treadmill exercise echocardiograms to determine the prognostic value of a normal exercise echocardiogram in patients evaluated for suspected coronary artery disease. There were 77 men and 71 women with a mean age of 52.5 years and a pretest likelihood of coronary artery disease of 39%. Patients were followed for a mean duration of 28.4 +/- 8.5 months. The exercise ECG was abnormal in 69 patients (47%) including 28 who had ischemic responses. Cardiac events occurred in six patients, three with normal and three with abnormal exercise ECGs. Events occurred only in those patients (6 of 68) who exercised to work loads less than 6 METs or who achieved less than 85% of the age-predicted maximal heart rate. Three patients had coronary artery bypass grafting for angina from 10.5 to 22.5 months after echocardiography. A fourth patient had bypass grafting for mild single-vessel disease at the time of mitral valve replacement. Two patients had myocardial infarctions (0.85% per year) at 7.5 and 41 months after echocardiography. There were no deaths. Coronary revascularization is infrequently required in the 28 months after a normal exercise echocardiogram. A normal exercise echocardiogram in a patient with good exercise capacity was predictive of an excellent prognosis, even in those who had abnormal exercise ECGs. Myocardial infarction and death were rare events, even in patients with decreased exercise capacity.

An echocardiographic index for separation of right ventricular volume and pressure overload.

Abnormal motion of the interventricular septum has been described as an echocardiographic feature of both right ventricular volume and pressure overload. To determine if two-dimensional echocardiography can separate these two entities and distinguish them from normal, geometry and motion of the interventricular septum in short-axis views of the left ventricle were evaluated in 12 normal subjects and 35 patients undergoing cardiac catheterization. Thirteen of the 35 patients had uncomplicated atrial septal defect with associated right ventricular volume overload, but no elevation in pulmonary artery pressure. The 22 remaining patients had a pulmonary artery systolic pressure greater than 40 mm Hg and, thus, constituted the group with right ventricular pressure overload. An eccentricity index, defined as the ratio of the length of two perpendicular minor-axis diameters, one of which bisected and was perpendicular to the interventricular septum, was obtained at end-systole and end-diastole. In all normal subjects, the eccentricity index at both end-systole and end-diastole was essentially 1.0, as would be expected if the left ventricular cavity was circular in the short-axis view. In patients with right ventricular volume overload, the eccentricity index was approximately 1.0 at end-systole, but was significantly increased at end-diastole (mean eccentricity index = 1.26 +/- 0.12) (p less than 0.001). In patients with right ventricular pressure overload, the eccentricity index was significantly greater than 1.0 at both end-systole and end-diastole (1.44 +/- 0.16 and 1.26 +/- 0.11, respectively) (p less than 0.001). These results suggest that an index of eccentric left ventricular shape which reflects abnormal motion of the interventricular septum can be defined.(ABSTRACT TRUNCATED AT 250 WORDS)

"Left main equivalent" coronary artery disease: its clinical presentation and prognostic significance with nonsurgical therapy.

The clinical characteristics and nonsurgical prognosis of 55 patients with "left main (LM) equivalent" coronary artery disease (CAD) were evaluated and defined as: (1) greater than or equal to 75% diameter reduction of the left anterior descending coronary artery (LAD) before the takeoff of any large septal perforator or anterolateral (diagonal) branches; (2) greater than or equal to 75% diameter reduction of the left circumflex artery (LC) before the takeoff of any large marginal branch; and (3) absence of greater than or equal to 50% stenosis of the LM coronary artery. Compared with nonsurgically treated patients with greater than or equal to 75% stenosis of the LM artery, patients with LM equivalent CAD had a shorter duration of symptoms (median of 51 months vs 66 months) and more often had a Q wave on the electrocardiogram (60 vs 39%). Survival in patients with LM equivalent CAD (78% at 1 year and 55% at 5 years) was better than that in patients with LM disease with nonsurgical therapy (65% at 1 year and 40% at 5 years) (p = 0.02), although the rate of freedom from cardiovascular events was not significantly different. Compared with other nonsurgically treated patients with 2- or 3-vessel CAD involving the LAD and LC (28 and 42%, respectively, with progressive angina), patients with LM equivalent CAD had more severe anginal symptoms (55% with progressive angina) and a longer duration of symptoms (medians of 20 months in 2-vessel CAD, 36 months in 3-vessel CAD and 51 months in LM equivalent CAD).(ABSTRACT TRUNCATED AT 250 WORDS)

Accuracy and interobserver variability of coronary cineangiography: a comparison with postmortem evaluation.

The accuracy of interpretation of coronary cineangiography by two independent observers was tested against postmortem findings in 27 patients who died within 6 months of cardiac catheterization. Variations in cineangiographic interpretations between the angiographers were also evaluated. Two patients had normal coronary arteries, while the remaining 25 patients had significant coronary artery disease. Significant stenosis was defined as 75% or greater reduction in luminal diameter. Of 326 coronary segments that could be evaluated postmortem, 15% could not be evaluated cineangiographically. The respective overall accuracy of the two observers was 89 and 88% with an accuracy of 96 and 100% for the left main coronary artery, 91 and 93% for the left anterior descending artery, 84 and 86% for the right coronary artery and 89 and 79% for the left circumflex coronary artery. Cineangiographic assessment of luminal status distal to a significant proximal lesion was possible in more than 70% of major vessels with accuracy levels of 86% for both observers. Of 96 distal vessels inadequately opacified cineangiographically, 49 (52%) were found to be free of significant lesions. Both angiographers agreed in their assessment of 86% of the 340 coronary segments. Interobserver agreement was significantly better for the left main, right and left anterior descending coronary arteries than for the left circumflex coronary artery (p less than 0.05). Accuracy was 93% for 244 segments that were adequately opacified and assessed the same by both angiographers. Cineangiography can thus be used to evaluate coronary anatomy with a high degree of accuracy and minimal interobserver variability.

Hypersensitive carotid sinus syndrome manifested as cough syncope.

We describe a patient with cough syncope who was found to have carotid sinus hypersensitivity with mixed cardioinhibitory and vasodepressor responses. Symptoms were ameliorated by denervation of the more hypersensitive carotid sinus. Spontaneous atypical Wenckebach cycles in this patient were caused by the combined hypersensitive cardioinhibitory and vasodepressor responses. This report stresses the importance of checking blood pressure as well as heart rate in all patients in whom carotid sinus syndrome is suspected.

The prognostic spectrum of left main stenosis.

Three-year survival for 163 consecutive medically treated patients with 50% or greater left main stenosis was 50%. Survival was significantly higher for patients with 50 to 70% left main stenosis (one and three-year survivals of 91% and 66%) than for patients with 70% or greater left main stenosis (one and three-year survivals of 72% and 41%). In fact, left main lesions of less than 70% were not associated with the increased risk usually attributed to patients with left main stenosis. A number of noninvasive and catheterization characteristics were significant predictors of survival for patients with 70% or greater left main stenosis. Noninvasive descriptors defined a low risk subgroup (one and three-year survivals of 97% and 74%) and a high risk subgroup (one- and three-year survivals of 59% and 25%). These observations have important implications both in assessing therapeutic interventions and in managing individual patients.

Hospital discharge one week after acute myocardial infarction.

Sixty-seven consecutive patients who had suffered an acute myocardial infarction but no serious complications during the first to fourth hospital days were considered for a trial of hospital discharge at one week. Thirty-three of the 67 patients were discharged at one week, the remainder having a mean hospital stay of 11 +/- 2 days. The incidence of late complications and recurrent infarctions, as well as mortality and functional status, were determined in all patients six months after discharge. No serious complications occurred in either subgroup within three weeks after discharge. There were no deaths in either subgroup and no difference in functional status at six months. Patients without serious complications during the four days after an acute myocardial infarction can be spared the economic costs and psychologic stress of prolonged hospitalization.

Cardiac arrest complicating acute myocardial infarction: predictability and prognosis.

Eleven percent of 905 consecutive patients with acute myocardial infarction admitted to the coronary care unit at Duke University Medical Center experienced cardiac arrest. Subgroups of patients at high and low risk for cardiac arrest were identified. Cardiac arrest was experienced by 17 percent of patients with signs of heart failure on admission but by only 3 percent of patients without diabetes mellitus, prior myocardial infarction or heart failure by history or on admission. Only 59 percent of patients with cardiac arrest survived hospitalization compared with 88 percent of those without cardiac arrest. Long-term survival for the 765 hospital survivors was significantly greater in the group without than in the group with arrest at each yearly interval from 1 through 5 years; the 2 year survival rate was 50 and 77 percent, respectively, in these two groups. Many of the deaths among the hospital survivors occurred in patients with signs of heart failure during hospitalization. Among 668 hospital survivors who had mild or no heart failure during hospitalization, cardiac arrest continued to be a significant predictor of mortality. The mode of death among hospital survivors did not differ in the groups with and without cardiac arrest; for example, the incidence rate of sudden death in the two groups was 44 and 37 per cent, respectively. In light of recent reports suggesting that the prophylactic use of antiarrhythmic agents can virtually eliminate virtually fibrillation during the hospital phase of acute myocardial infarction, we contend that such use may substantially reduce both long-term and hospital mortality after acute myocardial infarction.

The relationship of patient selection to prognosis following aortocoronary bypass.

Operative mortality for the first 787 patients who underwent aortocoronary bypass at Duke University Medical Center was 9.7%. Within 699 patients who underwent elective bypass only, operative mortality was 8.8% before January 1, 1972, and 5.4% subsequently. This apparent variation in operative mortality over time was largely a consequence of changing patterns of patient selection, i.e., a two- to three-fold decrease in the prevalence of ventricular dysfunction. Since January 1, 1972, operative mortality for 444 patients with mild or no heart failure who underwent elective bypass only was 5.0%. The 55 patients with left main disease had 12.7% operative mortality. In the 192 patients without left main disease who had one- or two-vessel disease, operative mortality was 1.0%, whereas, 197 patients with three-vessel disease had a 6.6% operative mortality. The 103 patients with three-vessel disease less than 50 years of age underwent operation with a 2.9% mortality. Although these results demonstrate that selected patients may undergo operation with a mortality approaching 1%, it is not clear that only such low risk patients should be offered surgery. Accurate estimates of benefits and risks of aortocoronary bypass surgery are necessary in the management of specific patients.