Quantum chromodynamics at 6/g2=5.60.
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Biomedical subjects
Publications and source records attributed to S Gottlieb.
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A series of 198 consecutive patients with acute myocardial infarction were prospectively studied before hospital discharge and during 24.0 +/- 8.6 months of follow-up. A predischarge thrombus was found in 38 (31%) of 124 patients with anterior infarction but in none of 74 patients with inferior infarction (p less than 0.001). Early thrombolytic therapy in 34 patients did not decrease the rate of thrombus occurrence. Acute anterior infarction, ejection fraction less than or equal to 35% and apical dyskinesia or aneurysm (but not akinesia) were significantly related to the appearance of thrombus during hospitalization by stepwise logistic regression analysis. Echocardiographic follow-up of 159 patients for at least 6 months (mean 26.6 +/- 8.4) revealed that thrombus disappeared in 14 (48%) of 29. Disappearance of thrombus was related to predischarge apical akinesia (but not dyskinesia) and to warfarin therapy during the follow-up period. A new thrombus first appeared after hospital discharge in 13 of 130 patients, and in 7 of the 13 it resolved during further follow-up. Thus, 30% (13 of 42) of thrombi in these patients appeared after discharge from the hospital. Three factors were related to occurrence of new thrombi during the follow-up period: deterioration in left ventricular ejection fraction, predischarge ejection fraction less than or equal to 35% and ventricular aneurysm or dyskinesia. Systemic embolism occurred in six patients, all with a predischarge thrombus (p less than 0.001). Mobility of the thrombus was the only variable significantly related to subsequent embolic events (p = 0.001) by logistic regression analysis. Thus, the predischarge echocardiogram identifies patients with thrombus and those at highest risk of embolic events. It can indicate patients who are likely to have thrombus resolution and those at risk of developing a new thrombus after hospital discharge. Follow-up echocardiograms may help in guiding the length of long-term anticoagulant therapy. Four additional patients with a predischarge apical mobile thrombus (not part of the consecutive series) received thrombolytic therapy. In two of the four, lysis of thrombus was achieved without complications, but systemic embolism occurred in the other two, and proved fatal in one.
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Genetic studies were done with Candida albicans CBS 562. Various auxotrophs were isolated following mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. SAG5 (his4C), a stable histidine auxotroph defective in histidinol dehydrogenase activity, was characterized and chosen for further molecular studies. Therefore, the C. albicans HIS4 gene was isolated. The gene was obtained from a genomic library of the wild-type strain, which was constructed in plasmid YEp24. The HIS4 gene was isolated by transformation of a Saccharomyces cerevisiae strain that carried a his4 mutation. The isolated C. albicans HIS4 gene complemented S. cerevisiae his4A, his4B, his4C, and his4ABC mutant strains, which indicates that the clone contains the entire HIS4 gene. The gene was isolated on plasmid pSTC7, whose physical map was constructed with BamHI, SalI, and EcoRV restriction endonucleases, locating the HIS4 gene on a 14-kilobase-pair DNA fragment. Hybridization experiments with HIS4 and C. albicans genomic DNA showed correspondence between the restriction patterns of the gene with that of the chromosomal DNA, indicating that the gene originates from C. albicans and appears in a single copy. Chromosomes of C. albicans CBS562 and four other strains were resolved by orthogonal-field alteration gel electrophoresis. The electrokaryotyping results showed heterogeneity in chromosomal sizes. The electrokaryotyping of CBS 562 showed a resolution of six chromosomal bands, three of which seemed to be doublets. The C. albicans HIS4 gene was located on the largest resolvable chromosome in all of the strains.
Prognosis in classically described dilated congestive cardiomyopathy has been reported to be related to ventricular size. Mildly dilated congestive cardiomyopathy (MDCM) has been defined as end-stage heart failure of unknown etiology (New York Heart Association class IV, left ventricular ejection fraction less than 30%), occurring with neither typical hemodynamic signs of restrictive myopathy nor significant ventricular dilatation (less than 15% above normal range). The present study includes follow-up in 12 nontransplant patients. In the first 4 months after diagnosis, two patients improved and are living, and two showed cardiac dilation and clinical deterioration and died. Six of the remaining eight with persistent MDCM died (four with intractable heart failure and two, sudden deaths) without change in ventricular size before death, despite medical therapy over 20 +/- 8 months. Eight comparable transplanted patients with persistent MDCM demonstrated improved total survival by life table analysis (p less than 0.05). A family history of congestive cardiomyopathy was found in nine of 16 patients (56%) with persistent MDCM. Nontransplant patients were older (p less than 0.02), but other findings were similar in the two groups. Endomyocardial biopsies available in 14 of 16 cases showed little or no myofibrillar loss in spite of severe hemodynamic impairment. The degree of myofibrillar loss did not correlate with hemodynamic parameters but showed good correlation with left ventricular size, that is, five of six patients with no myofibrillar loss had normal ventricular size, whereas all eight patients with mild myofibrillar loss had mild cardiomegaly (p less than 0.002). Our current experience suggests a somewhat variable but negative prognosis after prospective diagnosis of MDCM, with poor survival in patients with persistence of the original diagnostic features during follow-up. Preservation of heart size in MDCM is probably related to lack of significant myofibrillar loss. Thus, irrespective of heart size or myofibrillar preservation on biopsy, heart transplantation should be strongly considered in MDCM if signs of severe cardiac dysfunction persist despite therapy.
The phase, relative to the arterial pressure, of cyclically varying integrated backscatter from canine myocardium was measured at normal and reduced coronary blood flow levels and was found to become more randomized with decreasing flow. The phase, modeled as a von Mises distribution on a unit circle which is very similar to the normal distribution on the line, is characterized by a mean (mu 0) and a concentration or width parameter (kappa). kappa is used to characterize the degree of randomization. The von Mises distribution provides an excellent fit to measured data (p less than 0.01). Hypothesis tests performed on the data for various coronary flow levels indicate that the phase distribution for normal coronary flow level is significantly different from the distributions at other flow levels (p less than 0.05). The results suggest that the parameter kappa may be used for differentiating normal and ischemic myocardium.
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The yeast SIR2 gene is involved in regulating nucleosome phasing and transcription in the mating type system. We have found that SIR2 also plays another important role in the cell. Specifically, in wild-type SIR2 strains recombination between the tandemly repeated ribosomal RNA genes is depressed. In sir2 mutants, both mitotic and meiotic intrachromosomal recombination increase 10- to 15-fold. In striking contrast to its effect on rDNA, the SIR2 gene does not affect intrachromosomal recombination between non-rDNA gene duplications. Furthermore, in the absence of the SIR2 gene product, rDNA acquires a partial dependency on recombination gene functions (RAD50 and RAD52) that are normally dispensable for exchange in the rDNA array. Thus, SIR2 may function in excluding the rDNA region from the general recombination system. Here we demonstrate that SIR2's effect is not restricted to controlling mating type expression, but rather that SIR2 functions in a more general way in the genome.
The prognosis of patients recovering from acute myocardial infarction (MI) depends mainly on their residual left ventricular (LV) function. In patients with asymmetric septal hypertrophy (ASH) who are recovering from MI, a larger functioning myocardial mass may remain. However, the frequency of ASH in these patients has not yet been described. Predischarge echocardiography, radionuclide ventriculography, and treadmill stress tests were performed in 403 consecutive patients who had recovered from acute MI. Eighty-eight patients (22%) had ASH with septal thickness greater than or equal to 1.3, and 32 (8%) had septal thickness greater than or equal to 1.5 cm. One hundred thirty-six patients who had recovered from a first MI and had no ASH served as control subjects. Left ventricular ejection fraction (LVEF) in the group with ASH was significantly higher than in control subjects (61% vs 50%; p = 0.0001). LV end-diastolic diameter (LVD(d] and E point septal separation (EPSS) were smaller in the group with ASH (4.9 cm and 5.4 mm) than in the control group (5.5 cm and 10.5 mm). The frequency of positive treadmill test results, angina pectoris, recurrent MI, heart failure, and death during a 22-month follow-up period was similar in both groups. Fifty subjects in the control group were matched with 50 patients from the group with ASH on the basis of maximal level of creatine phosphokinase, location of infarct, and presence or absence of hypertension, and the difference between the two groups was even more marked (LVEF 48% vs 61%, respectively; p = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)
This study shows that RAD50, a yeast DNA repair gene required for meiotic interchromosomal exchange between homologs, also is required for meiotic intrachromosomal recombination. However, only intrachromosomal events in nonribosomal DNA are dependent on RAD50; those in ribosomal DNA (rRNA-encoding DNA) occur in the absence of this gene. Furthermore, nonribosomal DNA sequences retain their RAD50-dependence even when inserted into the ribosomal DNA array. We argue that these data provide evidence for at least two pathways of meiotic intrachromosomal recombination whose activity depends on the specific sequences involved or their structural context in the chromosome. In contrast to its role in meiosis, RAD50 is not required for either inter- or intrachromosomal spontaneous mitotic recombination.
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This study assessed the prognostic significance of ischemic changes during daily activity as recorded by ambulatory electrocardiographic monitoring in a group of 224 low-risk postinfarction patients. Of the 224 patients studied, 74 (33%) had transient ischemic episodes on Holter monitoring. During the 28 months of follow-up the frequency of cardiac events (cardiac death, reinfarction, hospitalization for unstable angina, balloon angioplasty or coronary bypass surgery) was 51% among those with ischemic episodes on Holter monitoring, compared with 12% in those without such changes (p less than 0.0001). The 74 patients with positive results in their exercise tests and Holter monitoring had a 51% event rate, compared with 20% among the 44 patients with a positive exercise test result but negative Holter results (p less than 0.001). The event rate in those without ischemic changes either on the exercise test or on Holter was only 8.5%. Among patients with good (greater than 40%) or reduced (less than 40%) left ventricular ejection fraction, those with transient ST depression on Holter had a significantly higher cardiac event rate compared with those without it. A similar event rate was found in patients with only silent, only symptomatic and with silent and symptomatic ischemic episodes.
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Sinus node and atriventricular (A-V) nodal functions were evaluated by right atrial pacing in 220 consecutive patients recovering from acute myocardial infarction (AMI), 10-28 days after the infarct (mean = 14 days). In the 188 patients in whom a pacing rate of 120 beats/min could be achieved, sinus node recovery time, corrected sinus node recovery time (CSNRT) and total recovery time were correlated to infarct site and the presence or absence of myocardial ischemia. Sinus node recovery time and total recovery time were significantly longer in patients with inferior (1,153 + 28 and 3,129 + 179 ms, respectively) or non-Q-wave infarct (1,112 + 28 and 3,730 + 266 ms, respectively), than in patients with anterior infarct (1,044 + 20 and 1,153 + 28 ms, respectively). The parameters were within the reported normal range. When corrected for heart rate (CSNRT), these differences were no longer present. The presence or site of residual ischemia during right atrial pacing did not affect the sinus nodes parameters. A-V nodal function, studied in all 220 patients, was assessed by the appearance of second-degree A-V block at pacing rates below 120 beats/min and by measuring the shortest atrially paced cycle length with 1:1 A-V conduction. Second-degree A-V block appeared at a similar frequency in different AMI locations. Thus, sinus and A-V node functional status in patients recovering from AMI are not affected by infarct site or by the presence or absence of residual myocardial ischemia.
Twelve consecutive patients who developed torsade de pointes (polymorphous ventricular tachycardia with marked QT prolongation, TdP) over a 4 year period were treated with intravenous injections of magnesium sulfate. In nine of the patients a single bolus of 2 g completely abolished the TdP within 1 to 5 min, and in three others complete abolition of the TdP was achieved after a second bolus was given 5 to 15 min later. Nine of the patients also received continuous infusion of MgSO4 (3 to 20 mg/min) for 7 to 48 hr until the QT interval was below 0.50 sec. In nine of the 12 patients the TdP was induced by antiarrhythmic agents. The QT interval preceding TdP ranged from 0.54 to 0.72 sec. After the MgSO4 bolus, which prevented the recurrence of TdP, no significant changes were observed in the QT interval. There were no side effects of this treatment. In eight of the 12 patients potassium levels before the TdP were below 3.5 meq/liter; magnesium levels were available in eight patients before TdP, and were normal in all. Five additional patients with polymorphous ventricular tachycardia but normal QT intervals (non-TdP patients) received two to three boluses of MgSO4. This treatment was ineffective in all, but they responded to conventional antiarrhythmic therapy. Thus, MgSO4 is a very effective and safe treatment for TdP, and its application is rapid and simple. Its use is therefore recommended as the first line of therapy for TdP.
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