Adenocarcinoma of the endometrium: analysis of 256 cases with carcinoma limited to the uterine corpus. Pathology review and analysis of prognostic variables.
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Adenocarcinoma↗
Biomedical subjects
J Ross
Publications and source records attributed to J Ross.
Left ventricular geometry during partial and complete coronary occlusion in the conscious dog.
Seven dogs were instrumented with a left ventricular micromanometer and pairs of ultrasonic crystals to measure left ventricular wall thicknesses (control and ischemic regions) and short and long left ventricular axes; cuff occluders were placed around the left circumflex coronary artery and the inferior vena cava. Measurements were performed at rest, after 2 min of partial and complete coronary occlusion, and 1 and 10 min after release of partial and complete coronary occlusion. Left ventricular wall thickness in the ischemic region showed reduced systolic thickening during partial coronary occlusion and systolic thinning during complete coronary occlusion. During diastole, at zero pressure (inferior vena cava obstruction) the left ventricular short axis was unchanged during partial coronary occlusion but significantly increased (creep) during complete coronary occlusion (P less than 0.05), whereas after release of both partial and complete coronary occlusion the short axis at zero pressure decreased significantly (P less than 0.025). Left ventricular wall thickness at zero diastolic pressure in the ischemic region was significantly thinner during complete coronary occlusion than during control and significantly thicker (reactive hyperemia) 1 min after release of both partial and complete coronary occlusion. The long left ventricular axis remained unchanged during the entire experiment. At end-diastole, the long/short axis ratio was normal during partial (1.72; control 1.68; NS) and complete coronary occlusion (1.69; NS), but it decreased significantly from control of 2.10 to 1.99 with partial coronary occlusion and 1.85 with complete coronary occlusion (P less than 0.01). The changes in the L/S ratio during partial and complete coronary occlusion were proportional to changes in left ventricular chamber volume (correlation coefficient 0.94). Our data show that left ventricular shape remains normal at end-diastole during partial and complete coronary occlusion but becomes significantly more spherical at end-systole, with reduction of the normal tendency for the ventricle to become more elliptical during systole. These elliptical and spherical shape changes of the left ventricle during partial and complete coronary occlusion appear to be closely related to the chamber volume.
Animals↗
Lipophilic 5'-(alkyl phosphate) esters of 1-beta-D-arabinofuranosylcytosine and its N4-acyl and 2,2'-anhydro-3'-O-acyl derivatives as potential prodrugs.
Lipophilic 5'-(alkyl phosphate) esters of 1-beta-D-arabinofuranosylcytosine (ara-C) and several N4-acyl and 3'-O-acyl-2,2'-anhydro derivatives of ara-C were synthesized as potential prodrugs of ara-C 5'-monophosphate (ara-CMP). Alkylphosphorylation of ara-C, N4-palmitoyl-ara-C, and N4-stearoyl-ara-C was achieved in a single continuous operation by allowing the nucleoside to react with POCl3 in trimethyl or triethyl phosphate and adding the appropriate anhydrous alcohol directly to the intermediate phosphorodichloridate without isolation. Similar reaction of cytidine yielded cytidine 5'-(alkyl phosphate) esters, which on treatment with myristoyl or palmitoyl chloride in the presence of boron trifluoride gave 3'-O-acyl-2,2'-anhydro-ara-C 5'-(alkyl phosphate) esters. Ara-C 5'-(n-butyl phosphate) (1b), N4-palmitoyl-ara-C 5'-(n-butyl phosphate) (1h), and 2,2'-anhydro-3'-O-palmitoyl-ara-C 5'-(n-butyl phosphate) (2h) were tested against L1210/ara-C leukemia in mice in the hope that this kinase-deficient tumor would respond to treatment with these "prephosphorylated" derivatives, but no activity was observed. Of the simple 5'-(alkyl phosphate) esters tested in culture against l1210 leukemic cells, only ara-C 5'-(glyceryl phosphate) (1g) showed toxicity comparable to ara-CMP (ID50 = 0.35 and 0.65 microM, respectively), suggesting that beta-hydroxyalkyl phosphate esters may be worthwhile to examine further as prodrugs of ara-CMP.
Animals↗
Entrainment and resonance in glycolysis.
We have proposed a comprehensive model for the glycolytic reaction mechanism and have shown the possibility of self-tuning to resonance, with consequent increase in efficiency of energy transduction by separating the model into two subsystems: one for the phosphofructokinase (PFKase; ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) reaction and the other for the pyruvate kinase (PKase; ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) reaction. The purpose of this article is to present an alternative theoretical approach-one more directly applicable to experimental situations-for the detection of these effects without the need for any decomposition. The approach consists in studying the response of such systems to externally applied periodic perturbations inside the fundamental entrainment band by computation. We show, in agreement with previous results obtained for simpler reaction schemes, that large increases and decreases in dissipation may occur in a narrow range of the period of entrainment of the entire mechanism. If the period of the autonomous glycolytic oscillation past marginal stability approaches a value, T(0) (lim), that is close to the period of relaxation oscillation of the PKase subsystem, T(PKase), then tuning of the primary oscillophor, the PFKase system, has been effected by the PKase system; in such cases we predict, for larger values of the amplitude of perturbation, two peaks in the response spectrum: one near the period of the autonomous oscillation and the other at the period of the PKase system. For small amplitudes of perturbation, there is only one resonance peak near the period of the autonomous oscillation. If T(0) (lim) is not close to T(PKase), then there is only one resonance peak for small and large amplitudes of external perturbations. Our computer results lead to a classification of the chemical species in the reaction mechanism into two categories. The first category has the following two properties. (i) When fundamental entrainment occurs, the amplitude of the response in all species in the reaction mechanism is largest when the oscillation in the perturbation of a chemical species is in phase with the oscillation of that variable in the mechanism. (ii) If the amplitude of the external periodic perturbation is monitored in time so as to keep that variable in the mechanism always constant, then there is no oscillatory response in the whole reaction pathway. The variables having these two properties have been found to be essential for the generation of self-sustained oscillations in our model. For the second category neither of these two properties holds.
Glucose↗
Diastolic myocardial wall stiffness of the left ventricle in chronic pressure overload.
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Animals↗
Uterine papillary serous carcinoma: a highly malignant form of endometrial adenocarcinoma.
A review of 256 cases of pathologic Stage I uterine adenocarcinoma treated at Stanford University Hospital revealed 26 cases of uterine papillary serous carcinoma (UPSC), a clinically aggressive and morphologically distinct variant of adenocarcinoma which closely resembles ovarian papillary serous carcinoma. These lesions are easily recognized by microscopic examination and typically feature a high degree of cytologic anaplasia and a papillary growth pattern. Invasion of the lymphatics has been a frequent finding. The relapse rate among patients with pathologic Stage I UPSC was 50% (13/26), five times the rate which would have been predicted by the incidence of UPSC. Patients with Stage I UPSC fared significantly worse than the group of nonpapillary grade II or grade III adenocarcinomas (p less than 0.0001). Forty percent of Stage I UPSC patients had deep myometrial invasion, as compared with 12% of those with all other histologic types of adenocarcinoma (p = 0.001). Women with UPSC deeply invading the myometrium tended to do worse than those with deeply invasive lesions of the more usual endometrioid type as reflected by relapse rates (after surgery alone) of 63% and 30%, respectively. Of seven Stage I corpus carcinoma patients whose initial site of failure was in the upper abdomen, six had UPSC. Thus, UPSC shares the tendency of its ovarian counterpart to spread over peritoneal surfaces. In addition to the original study group of 26 Stage I patients, 34 patients with more advanced stages of UPSC were also reviewed. Of these, 26 have been followed and four survive. Eleven of these women presented or relapsed with abdominal carcinomatosis. UPSC is a clinically aggressive neoplasm which should be distinguished from other types of primary endometrial adenocarcinoma. In cases of invasive UPSC the mode of spread, similar to that of ovarian surface epithelial carcinomas, suggests the need for adjuvant upper abdominal and pelvic irradiation or effective chemotherapy.
Carcinoma, Papillary↗
Selective depression of motion sensitivity during saccades.
1. Horizontal gratings flashed for 20 ms were used to compare visual contrast sensitivity during horizontal saccades with sensitivity during normal vision, at three luminance levels, 4 X 10(2), 4 X 10(-2), and 4 X 10(-4) cd/m2. 2. Greatest sensitivity loss during saccades was found at low spatial frequencies. There is little or no loss at high spatial frequencies. 3. As luminance level is decreased there is a decrease in the spatial frequency below which saccadic sensitivity loss occurs. This shift in spatial frequency with luminance level, considered in conjunction with measurements of stationary and drifting gratings, indicates the functional involvement of movement sensitive mechanisms in saccadic sensitivity loss. 4. At the two lower luminance levels (4 X 10(-2) and 4 X 10(-4) cd/m2) sensitivity during saccades is greater than normal at high spatial frequencies. This enhancement of sensitivity was confirmed by forced choice measurements. 5. It was also shown that sensitivity to abrupt changes in the trajectory of moving gratings is lowered during saccades. 6. It is concluded that mechanisms sensitive to movement and transients are damped during saccades, so preventing perception of image motion during saccades and thereby preserving visual stability.
Eye Movements↗
Isoproterenol-induced myocardial dysfunction in dogs with coronary stenosis.
Stress-induced regional myocardial ischemia in the presence of mild coronary stenosis was studied in five dogs 2-4 wk after implantation of pairs of ultrasonic crystals to measure left ventricular wall thickening (% delta WT) and subendocardial segmental shortening (% delta L). Isoproterenol (0.2 micrograms.kg-1.min-1) was infused before and after production of coronary stenosis, which produced no resting dysfunction. During isoproterenol infusion with coronary stenosis % delta WT and subendocardial % delta L were significantly decreased although blood flow was comparable to conditions at rest, indicating that the demand for blood flow exceeded supply. Linear regression analysis of mean transmural blood flow versus % delta WT during isoproterenol demonstrated that wall thickening was significantly related to changes in mean blood flow: y (percentage wall thickening) = 27.5 X (transmural blood flow) -8.2 (r = 0.83); likewise % delta L was significantly related to subendocardial blood flow during isoproterenol infusion: y (percentage shortening) = 17.1 X (subendocardial blood flow) -0.4 (r = 0.85). These results indicate that both regional % delta WT and % delta L sensitively reflect the adequacy of myocardial perfusion even during stress-induced changes in myocardial O2 demands and blood flow.
Animals↗
Myocardial blood flow and function with critical coronary stenosis in exercising dogs.
Critical stenosis of coronary arteries does not alter myocardial blood flow (MBF) at rest, but eliminates hyperemia and corresponds to a degree of arterial narrowing that expends subendocardial vasodilator reserve. Because subepicardial vasodilator reserve remains with critical stenosis at rest, we tested the significance of this reserve in six exercising dogs chronically instrumented to measure MBF (microspheres), regional function (systolic wall thickening with sonomicrometers), and coronary blood flow velocity (CBFV, pulsed Doppler). Critical stenosis produced with a hydraulic occluder limited CBFV and mean MBF to the resting level during treadmill exercise, but MBF was maldistributed. Subendocardial MBF decreased 50% (P less than 0.05) and subepicardial MBF increased 104% (P less than 0.01) compared with resting control conditions, suggesting that a transmural "steal" phenomenon had occurred, with augmented MBF in the subepicardial region at the expense of subendocardial MBF. Systolic wall thickening decreased markedly from 31.5 +/- 6.8 to 9.4 +/- 2.0% (P less than 0.01) during exercise, indicating that use of subepicardial vasodilator reserve with critical stenosis had little sustaining effect on regional contractile performance. Rather, subepicardial vasodilator reserve is potentially deleterious, inasmuch as a steal effect could contribute to reduced subendocardial perfusion, the primary determinant of systolic wall thickening.
Animals↗
Comparison of postpacing and exercise-induced myocardial dysfunction during collateral development in conscious dogs.
In 10 conscious dogs, a model was developed for studying regional contractile responses in a coronary collateral-dependent bed. Regional myocardial function was compared after terminating a maximum paced rate of 240 beats/min maintained for 3 minutes (postpacing period) with that during telemetry-monitored exercise at comparable heart rates (average 252 +/- 34 beats/min, duration 2.4 minutes) at different times during collateral development. Ultrasonic dimension gauges were used to measure control and ischemic segment (CS and IS) lengths and ischemic zone regional wall thickness (IW). An ameroid constrictor and a Doppler flow probe were placed around the left circumflex coronary artery, and pacing electrodes were sutured to the right ventricle. An average of 23 days postoperatively, coronary obstruction was complete. Studies at that time showed that percent shortening (% delta L) of IS and percent wall thickening (% delta W) of IW decreased after pacing to 57% and 35% of control, respectively, and during exercise to 37% of control. One week later (average 30 days postoperatively), significant depression of regional function no longer occurred postpacing. However, exercise at a comparable heart rate still provoked regional dysfunction in the collateral-dependent zone: Both IS% delta L and IW% delta W decreased to 51% of control. Regional function at rest did not differ during these studies. Thus, the effectiveness of the postpacing response for detecting limited collateral reserve was eliminated by further collateral development, but regional myocardial dysfunction during exercise stress served to detect ischemia despite increased collateral circulation.
Animals↗
Subepicardial segmental function during coronary stenosis and the role of myocardial fiber orientation.
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Animals↗
Mechanisms of proteinuria in human glomerulonephritis.
We evaluated glomerular barrier function in 28 patients with glomerulonephritis. Neutral dextrans of graded size were used to characterize the size-selective properties of the barrier. Charge selectivity was characterized by electrofocusing excreted urinary proteins. A fractional IgG clearance (relative to freely permeable inulin), smaller or greater than 100 x 10(-5) was used to distinguish patients with minor (group I, n = 13) and major (group II, n = 15) urinary IgG leakage, respectively. Fractional clearances of smaller dextrans (radii 20-50 A) were similar, but those of larger dextrans (radii 52-60 A) were elevated in group II relative to group I patients. A model of solute transport through a bimodal pore size distribution revealed the values for pore radius in the lower mode to approximate 51-55 A in both group I and group II patients. Pore radius in the upper mode, by contrast, was much larger in group II than in group I patients, approximating 87-97 vs. 72-77 A, respectively. Electrofocusing of urinary protein from group I patients revealed mostly albumin (isoelectric point 5.2). In group II patients, however, immunoglobulin excretion was copious. Moreover, the distribution of anionic, neutral, and cationic species (isoelectric points 5.5-8.5) in urinary and plasma eluates of IgG2 and IgG4 was similar. We conclude that when glomerulonephritis is associated with selective albuminuria, as in group I,, there is an isolated reduction of electrostatic retardation of relatively small anionic proteins. Major urinary IgG leakage (group II), however, appears to result from the development in the glomerular membrane of a subpopulation of enlarged pores that are highly permeable towards proteins of large size and varying charge.
Albuminuria↗
Cefotaxime, cefazolin, or ampicillin prophylaxis of febrile morbidity in emergency cesarean sections.
Cefotaxime, a new third-generation cephalosporin, was compared with ampicillin and cefazolin in a randomized double-blind trial to evaluate the efficacy of antibiotic prophylaxis of febrile morbidity associated with emergency cesarean sections. A 1-gm intravenous dose of one of the three antibiotics was given by bolus injection immediately after clamping of the umbilical cord and six and 12 hours later. All patients were in labor with membranes ruptured and had a temperature less than or equal to 37.8 C, and none had a history of penicillin or cephalosporin allergy. A total of 195 women were entered into the trial. Initially, the study included a placebo control group which was switched to ampicillin after 30 patients. Of the 188 evaluable patients, 51 of 59 (86.5%) ampicillin recipients, 59 of 67 (88.1%) cefazolin recipients, 48 of 55 (87.3%) cefotaxime recipients, and two of seven (28.5%) placebo recipients had uneventful postoperative courses. During the study, an additional 39 women who were in labor with ruptured membranes but who were allergic to penicillin or who declined antibiotic prophylaxis were classified as untreated patients and observed for postoperative complications. Standard febrile morbidity, primarily related to endometritis or wound infections, occurred in 6 of 59 (10.1%) ampicillin, 5 of 67 (7.5%) cefazolin, 5 of 55 (9.1%) cefotaxime, and 18 (40.0%) of placebo or untreated patients. Cefotaxime, cefazolin, and ampicillin were equally effective in reducing febrile morbidity in emergency cesarean sections.
Adolescent↗
The problem of the poorly differentiated sarcoma.
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Biopsy↗
Do coronary artery bypass operations prolong life?
Coronary artery bypass operations improve survival in patients with symptomatic left main coronary artery stenosis, but whether or not longevity is improved in other patients has been controversial. Small clinical studies, even when randomized, have not sufficiently controlled for the heterogeneous distribution of risk factors in patient cohorts treated medically and surgically. The first randomized study large enough to overcome such problems, the Veterans Administration Cooperative Study, showed that coronary artery bypass procedures prolonged survival only in the high-risk subgroup. The surgically treated patients suffered more perioperative morbidity and mortality and had worse long-term survival than similar patients operated on in more recent years. The European Coronary Surgery Study Group recently reported that the three-year to five-year survival of symptomatic patients with triple-vessel disease and normal left ventricular function was better if patients were randomly assigned to surgical therapy. The third and by far the largest randomized study, the Coronary Artery Surgery Study (CASS), has not yet reported long-term follow-up results. Large clinical studies, both randomized and nonrandomized, that have subgrouped patients by the number of diseased coronary arteries and by the degree of left ventricular dysfunction all show that survival with single-vessel disease is excellent and not improved by operation. Medically treated patients with double- and triple-vessel disease who have good left ventricular function generally now have a five-year survival greater than 85 percent and only two of the major studies suggest that it is improved by operation. The results of most studies, however, suggest that bypass operation prolongs survival in symptomatic patients when left ventricular dysfunction coexists with double- and triple-vessel disease. Continually improving surgical techniques may potentiate the small survival differences that are now apparent, but until then, because the survival differences are so small, it is recommended that limiting anginal symptoms remain the primary indication for a coronary bypass procedure for an individual patient.
Angina Pectoris↗
[Determinants of the diastolic pressure-volume relationship of the left ventricle: significance of myocardial ischemia and vena cava occlusion].
Diastolic pressure-volume relations of the left ventricle were studied in 7 dogs during partial and complete coronary occlusion. The pericardium was widely opened and the dogs were instrumented with a left ventricular micromanometer, cuff occluders around the left circumflex coronary artery and inferior vena cava, and ultrasonic crystals to measure control and ischemic wall thickness as well as both left ventricular long and short axes. Measurements were performed at rest and after 2 minutes of partial and complete coronary occlusion. The first experiment was performed without caval occlusion and a second experiment was carried out a few days later with caval occlusion. During partial coronary occlusion, no shift of the diastolic pressure-volume relationship was observed. However, during complete coronary occlusion the pressure-volume curve was shifted significantly upwards but no shift was observed when occlusion of the inferior vena cava was carried out. These findings suggest that the shift of the diastolic pressure-volume relationship during coronary occlusions (1) depends on the extent of myocardial ischemia and (2) is related to ventricular interaction since the shift was prevented by caval occlusion.
Animals↗
Adverse reactions to drugs.
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Drug-Related Side Effects and Adverse Reactions↗
Concentration oscillations and efficiency: glycolysis.
The oscillations observed in glycolysis are analyzed from the point of view of efficiency of free energy conversion. It is suggested that the mechanisms generating these oscillations may have evolved in order to reduce the dissipation of free energy.
Animals↗