Thermal counterparts of nonclassical states in quantum optics.
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Biomedical subjects
Publications and source records attributed to R Simon.
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The diagnostic approach to sore throat and its treatment by 7 doctors was studied in 692 community clinic patients. Redness of the throat, the commonest clinical feature in all age groups, was present in 88%. The prevalence of other clinical findings varied in the different age groups. 54% of the patients, most of whom were less than 13 years old, were treated initially with antibiotics. Most of the physicians prescribed penicillin V (average, 8.4 days). From 11 (13%) of the throat cultures taken from children under the age of 4, beta hemolytic streptococci (BHS) were grown. Based on throat cultures, antibiotics had been given unnecessarily in 53% of those in whom it was initially prescribed, and wrongly withheld in 10% of those who initially did not receive them. This study reveals an urgent need for a rapid and accurate method of detecting BHS in patients with sore throat.
Pharmacological inhibition of cell excitation during focal ischemia was studied in the rat middle cerebral artery occlusion model. The potent and selective N-methyl-D-aspartate antagonist CGS 19755, administered 5 minutes prior to or 5 minutes following permanent middle cerebral artery occlusion, caused a substantial decrease in infarct size, which was associated with reduction of postischemic cerebral glucose hypermetabolism. These data support a role for excitation-induced hypermetabolism in the pathogenesis of infarction following focal cerebrovascular occlusion.
Prognostic factors for long-term survival of 312 patients with diffuse large cell or immunoblastic non-Hodgkin's lymphoma are presented based on analysis of the multiinstitution clinicopathologic study sponsored by the National Cancer Institute. At the time of analysis, 75% of the patients had died and the median follow-up for patients still alive was 11 years. The distribution of Ann Arbor stages was 21% stage I, 32% stage II, 17% stage III, and 30% stage IV. Factors of prognostic significance for survival included age, stage, histologic subtype, presence of B symptoms, size of the largest lesion, number of extra-lymphoid organs involved, and extent of lymphatic involvement. Recursive partitioning analysis suggested a prognostic classification system based on stage, age, size of the largest lesion, and presence of mediastinal involvement. Stage I patient less than 50 years of age had a 10 year survival rate of 65% compared to 36% for older stage I patients. Stage II patients less than 65 years old without bulky lesions or mediastinal involvement had a 10 year survival rate of 45% compared to 10% for the poorer risk stage II patients. Although statistically significant prognostic factors were identified for the stage III/IV patients, they were not strong discriminants of 5-10 year survival rate. Because of the correlation among potential prognostic factors, there is no uniquely best classification system. Reasons for discrepancies among reported prognostic factor analyses are discussed, and a prognostic grouping that synthesizes our results with those of others is proposed.
Phase II studies of new medical treatments often use historical data on the standard treatment for comparative evaluation. Incorrectly disregarding inherent variability in the historical data may lead to erroneous conclusions regarding the efficacy of the experimental treatment. We propose an approach to phase II trial design which accounts for both inter-study and intra-study variation. Our results indicate that it is sometimes best to randomize a proportion of the patients to a control arm. We choose this proportion to maximize the precision of the estimated experimental treatment effect. We evaluate operating characteristics of the design numerically, and provide illustrations based on historical data from cancer chemotherapy trials.
The predictive power of a set of prognostic variables in a survival time model is a concept distinct from the statistical significance of the variables or the adequacy of the model fit. In this paper we discuss the importance of quantifying the predictive power of a prognostic model, and suggest measures of explained variation as a possible quantification. The important features of our approach are that (1) the measures are completely model-based; (2) a specification of the time range of interest is easily incorporated; and (3) the null models used for comparison are derived as mixtures of the predicted distributions.
In 70 patients without coronary disease we have compared three different principles to assess coronary flow reserve during diagnostic heart catheterization. Digital angiograms with ECG-triggered bolus injections of 4 to 8 ml of contrast medium at rest and after stimulation by dipyridamole (0,5 mg/kg i.v.) or papaverine (12,5 mg i.c.) were acquired in a 512 x 512 matrix at 8 bit resolution (ADAC 4100) and stored on a digital disk at 25 frames/sec. or 2 frames/cardiac cycle (PPR-mode). Angiograms were processed by cyclic R-wave-gated mask mode subtraction and coronary flow in the LAD area was assessed by three different approaches: 1. A traditional densitometric principle. 2. The 'CMAP' principle. 3. A modification of the Stewart-Hamilton principle comparing the total amount of contrast medium that enters the coronary circulation to the area of the contrast dilution curve in a fixed portion of the LAD. Flow was measured simultaneously during angiography using the thermodilution technique for coronary sinus/great cardiac vein flow. Drug stimulation resulted in an increased coronary blood flow up to five times of resting flow. Regression analysis revealed the following results for the assessment of the coronary flow reserved by digital angiography (y) when compared to thermodilution (x): [table: see text] Method 2 could be improved by replacing the density factor by morphometrically measured proximal LAD volume (y = 0.77x + 0.55; r = 0.78; SEE = +/- 0.43). In conclusion, our data suggest that the Stewart-Hamilton principle may be advantageous over time parameter-dependent approaches in the assessment of coronary flow reserve by digital angiography.
To assess whether pretreatment with intracoronary nifedipine protects the myocardium against acute ischemia induced by coronary occlusion, 18 patients were studied during coronary angioplasty of the left anterior coronary artery. After a control occlusion of 60 seconds, 0.1 mg nifedipine was injected and occlusion was repeated for 60 seconds. Before and during the occlusion period, pulmonary capillary pressure was measured and the intracoronary epicardial ECG was recorded. After intracoronary administration of nifedipine, the onset of the rise in diastolic filling pressure was delayed from 23 to 38 seconds (p less than 0.01) and the changes at 60 seconds of occlusion were reduced from 14 to 11 mmHg (p less than 0.05). Nifedipine delayed the appearance of ischemic ST-segment elevation in the intracoronary ECG from 11 to 21 seconds (p less than 0.01) and diminished the changes at 60 seconds of occlusion from 1.8 to 1.2 mV (p less than 0.05). These findings suggest that pretreatment with intracoronary nifedipine protects the myocardium against some of the mechanical and electrocardiographic consequences of regional ischemia during acute coronary occlusion.
In order to select insertion sequences able to promote transcription of flanking genes (ISp elements), three mobilizable RSF1010 derived vectors were constructed. Using promoterless antibiotic resistance genes, ISp elements ranging from 0.75 to 2.9 kb were isolated from Escherichia coli and Rhizobium meliloti. Restriction and hybridization experiments revealed that identical ISp elements could be isolated from different R. meliloti strains and that one of these is similar to an insertion sequence found previously in R. meliloti 2011.
In a series of 447 patients with single vessel angioplasty, 27 (6.0%) had acute thrombotic occlusion early after the procedure. They were treated with combined intracoronary (20 mg)/intravenous (50 mg) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and repeat mild balloon inflations. Reopening of the vessel was achieved in 22 patients (81.5%). Follow-up coronary angiography 24 to 36 h later revealed reocclusion in 12 patients (54.5%). Thrombin levels measured as thrombin-antithrombin-III complex in patients with successful thrombolysis and persistent patency decreased from 8.5 +/- 11.4 micrograms/liter at baseline to 3.5 +/- 1.4 micrograms/liter 120 min after the start of thrombolysis; these levels increased from 9.4 +/- 15.0 micrograms/liter at baseline to 15.7 +/- 13.5 micrograms/liter 120 min after the start of thrombolysis in the patients with unsuccessful thrombolysis or early reocclusion (p less than 0.05). When a borderline value for thrombin-antithrombin-III complex level of 6 micrograms/liter was selected to separate the two groups of patients, patients with an unfavorable clinical course were identified 120 min after the start of thrombolysis by levels greater than 6 micrograms/liter (sensitivity 100%, specificity 92.8%). Thus, after abrupt thrombotic vessel closure during coronary angioplasty, the short-term results of thrombolysis seem to be governed by the release of thrombin. In two thirds of patients, however, the thrombin release cannot be suppressed by concomitant aspirin and heparin therapy. Even after successful reopening of the vessel these patients should therefore undergo immediate aortocoronary bypass grafting.
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Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global and focal ischemia and hypoglycemia, and improves neurological outcome after experimental spinal cord injury. The present study examined the effects of the noncompetitive N-methyl-D-aspartate receptor blocker MK-801 on neurochemical sequelae following experimental fluid-percussion brain injury in the rat. Fifteen minutes after fluid-percussion brain injury (2.8 atmospheres), animals received either MK-801 (1 mg/kg, i.v.) or saline. MK-801 treatment significantly attenuated the development of focal brain edema at the site of injury 48 h after brain injury, significantly reduced the increase in tissue sodium, and prevented the localized decline in total tissue magnesium that was observed in injured tissue of saline-treated animals. Using phosphorus nuclear magnetic resonance spectroscopy, we also observed that MK-801 treatment improved brain metabolic status and promoted a significant recovery of intracellular free magnesium concentrations that fell precipitously after brain injury. These results suggest that excitatory amino acid neurotransmitters may be involved in the pathophysiological sequelae of traumatic brain injury and that noncompetitive N-methyl-D-aspartate receptor antagonists may effectively attenuate some of the potentially deleterious neurochemical sequelae of brain injury.
We report on the mobilization of shuttle plasmids from gram-negative Escherichia coli to gram-positive corynebacteria mediated by P-type transfer functions. Introduction of plasmids into corynebacteria was markedly enhanced after heat treatment of the recipient cells. High-frequency plasmid transfer was also observed when the restriction system of the recipient was mutated. On the basis of our data, we conclude that efficient DNA transfer from gram-negative to gram-positive bacteria, at least to coryneform bacteria, is conceivable in certain natural ecosystems.
Cosmid clones able to restore exopolysaccharide production in possibly insertion sequence element-induced surface mutants of Xanthomonas campestris pv. campestris were isolated. By fragment-specific Tn5-lac mutagenesis of one of the cosmids, pXCB1002, a new DNA region which is involved in exopolysaccharide biosynthesis and which is organized into at least 12 complementation groups was identified.
The adenovirus E1A gene product is a potent transcriptional activator and nuclear oncoprotein. Like other regulatory proteins, E1A has a short half-life, in the range of 30 to 120 min. This short half-life, which was measured in cells synthesizing E1A, is not observed in cells injected with E1A protein made in bacteria or in vitro. In these cases, E1A is essentially refractory to degradation. In an attempt to reconcile this apparent paradox, we suggested that E1A was marked for degradation during its synthesis. Furthermore, we showed that a domain in the amino terminus of E1A was required for rapid degradation in cells translating E1A mRNA (J. M. Slavicek, N. C. Jones, and J. D. Richter, EMBO J. 7:3171-3180, 1988). In this study, we have used Xenopus laevis oocytes injected with mRNAs encoding altered E1A proteins to show that the amino-terminal tetrapeptide Met-Arg-His-Ile is required for E1A degradation. Even conservative amino acid substitutions in this degradation sequence render it nonfunctional. This degradation sequence can function as a transferable signal, since it induces instability when fused to another normally stable protein. Furthermore, the degradation sequence requires a proximity of no more than six residues from the amino terminus for activity. These data suggest that a trans-acting factor recognizes the amino terminus of E1A during the translation of its message to mark the protein for subsequent destruction.
Demonstrating therapeutic equivalence of two treatments is the goal of many clinical trials. For instance, when the toxicity of an effective standard treatment is of concern, much effort is devoted to developing new therapies that would be both as effective and less toxic. In this paper we review the special characteristics of these trials and describe sequential monitoring of equivalence studies using repeated confidence intervals. We show how sequential monitoring may be of particular value in this setting and critically discuss the choice of some important design parameters. We also provide tables for use when planning a sequential equivalence trial.
Rupture of the ventricular septum is a rare complication of acute myocardial infarction. Time of diagnosis, hemodynamic condition, as well as duration and effectiveness of the preoperative treatment determine the clinical outcome after surgical repair. Since its introduction the bedside-applied Swan-Ganz catheter has maintained an important role for the rapid confirmation and quantitation of the infarct-induced ventricular septal rupture. We report on the clinical courses of two patients whose diagnoses were established by means of a fiberoptic-armed Swan-Ganz catheter. Accuracy of the measured oxygen saturation was controlled by in vitro gas analyses with heparinized blood samples. As compared to conventional methods the continuous in vivo oximetry by a fiber-optic system is a simple procedure which facilitates repeated shunt calculations during hemodynamic monitoring in critically ill patients.
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