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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 595 records · Page 33Linked to original sources

Noninvasive evaluation of normal and abnormal prosthetic valve function.

Noninvasive techniques are helpful in evaluating the function of mechanical prostheses and tissue valves. Combined phonocardiography and M-mode echocardiography together with cinefluoroscopy are the most useful noninvasive techniques in differentiating normal from abnormal metallic prosthetic valve function. The intensity of the opening and closing clicks and associated murmurs will depend on the type of prosthetic valve, the heart rate and rhythm and the underlying hemodynamic status. Arrhythmias or conduction disturbances, or both, may produce motion patterns that mimic some of the echocardiographic signs of malfunctioning prosthetic valves. Differentiation of thrombus formation or tissue ingrowth from paravalvular regurgitation or dehiscence is possible by noninvasive techniques. Disc variance, a potentially serious and lethal problem with the older Beall valves, can be readily detected by cinefluoroscopy and echophonocardiography. With regard to bioprosthetic valves, two-dimensional echocardiography is superior to M-mode echocardiography in detecting primary valve failure. In addition, detection of vegetations, valve alignment and ring and individual leaflet motion can be best accomplished by two-dimensional echocardiography. Of greater importance is the patient serving as his or her own control in the follow-up assessment of prosthetic valve function by noninvasive techniques.

Aortic Valve↗

Critique of a proposed stability criterion for chemical systems far from equilibrium.

Noyes [Noyes, R. M. (1981) Proc. Natl. Acad. Sci. USA 78, 7248-7249] has obtained a result for the Gibbs free energy per unit mass in a continuous flow stirred tank reactor, which states that the steady-state free energy increases monotonically with decreasing residence time for any stable stationary point. We show that his derivation is based on an erroneous stability criterion. We further investigate the dependence of the Gibbs free energy on residence time for the case of mass-action kinetics and ideal mixtures. We then apply this development to Schlögl's trimolecular reaction mechanism [Schlögl, F. (1971) Z. Phys. 248, 446-458] and show that Noyes' conjecture is violated for this simple example.

Journal Article↗

The failing heart and the circulation.

Altered loading conditions can sometimes produce serious heart failure, even though myocardial contractility is not depressed. The role of afterload in some forms of heart failure is emphasized, as are the conditions termed afterload mismatch, in which afterload is excessive "absolutely" or relative to diminished contractility. A related aspect is the role of the peripheral circulation.

Animals↗

Evidence that N-acetoxy-N-acetyl-2-aminofluorene crosslinks DNA to protein by a free radical mechanism.

A method was devised to quantitate N-acetoxy-N-acetyl-2-aminofluorene (N-AcO-AAF) induced crosslinking of the ionic complex between [methyl-3H]thymidine labeled pBR322 DNA and lysozyme. This involved chromatography of the modified complex on Sephadex CM 25 with a high salt buffer that dissociated the non-covalently bound complex and permitted early elution of unbound [3H]DNA. The crosslinked complex was then eluted with buffer at pH 10.5. The amount of crosslinking was a function of the carcinogen concentration in the reaction mixture containing the complex. Addition of the spin trap nitrosobenzene or the radical trap 2,2-diphenyl-1-picrylhydrazyl to the complex prior to the addition of N-AcO-AAF decreased crosslinking. Reaction of the carcinogen with a solution of [methyl-3H]thymidine labeled Escherichia coli DNA led to the formation of tritiated water that was azeotropically distilled from the mixture. If nitrosobenzene was added prior to the carcinogen, the amount of tritium water released was depressed. Addition of N-AcO-AAF to a mixture of acrylamide and bisacrylamide increased its relative viscosity. Far u.v. irradiation of the complex or reacting it with ammonium persulfate that dissociates to the sulfate anion radical, SO(4), induced crosslinking. While these observations support a free radical mechanism for crosslinking, whether the free radicals arise from heterolytic or homolytic cleavage of N-AcO-AAF remains undetermined.

2-Acetylaminofluorene↗

Mechanisms of cardiac contraction. What roles for preload, afterload and inotropic state in heart failure?

There is evidence that sarcomere length is maximal and changes little during chronic cardiac enlargement, and that the failing heart does not operate on a true descending limb of the Frank-Starling curve. However, increases of ventricular end-diastolic volume over time clearly are important at the geometrical level in maintaining stroke volume. When the preload reserve is fully utilized, afterload mismatch can exist in the steady state to produce operation of the heart on an apparent descending limb of cardiac function, and further afterload mismatch can be produced by pressure loading under these conditions. The treatment of acute experimental heart failure with a mixed vasodilator (nitroprusside) can lead to an increased cardiac output by afterload reduction only when the venous return curve does not shift downward; thus, the threefold larger shift of central blood volume to the periphery in heart failure (compared to normal) counter balances the venodilator action of nitroprusside. Whether or not the inotropic ceiling of failing myocardium can be reached by positive inotropic agents is unclear, but major hemodynamic benefits in heart failure with many potent inotropic drugs are associated with the direct vasodilating properties of these agents. Thus, there appears to be little role for the Frank-Starling mechanism at the sarcomere level, whereas afterload mismatch and its correction are of major importance provided the venous return can be increased. A degree of inotropic reserve also is available, even in the severely failing myocardium, but more research is needed on the potential costs and benefits of marked sustained inotropic stimulation.

Animals↗

Reappearance of epidermal Langerhans cells after PUVA therapy.

Epidermal Langerhans cells (LC) disappear during photochemotherapy (PUVA) with 8-methoxypsoralen (8-MOP) and long wavelength ultraviolet (UV-A) radiation. The time course of their disappearance during treatment and their reappearance after its completion was followed. Langerhans cells lost ATPase activity before they disappeared by ultrastructural criteria: thus 90% of ATPase-stained cells had disappeared after seven treatments (2 weeks) whereas it was only after fifteen treatments (5 weeks) that they were seen to be reduced on electron microscopy. Their numbers remained low throughout the course of treatment but they had returned to normal by 3 weeks after cessation of therapy. Since PUVA lamps also emit traces of medium wavelength UV (UV-B) the separate effects of UV-A and UV-B in the presence and absence of 8-MOP were examined. Within the dose range normally used for therapy, the LC disappeared only with the combination of UV-A and 8-MOP.

Adenosine Triphosphatases↗

Langerhans cells in autosomal dominant ichthyosis vulgaris.

Five patients with autosomal dominant ichthyosis vulgaris (ADI) were studied to see whether the abnormal keratinization was associated with disturbances of the appearance or the distribution of epidermal Langerhans cells (LCs). The LCs were identified by ATPase staining and electron microscopy. They were present in normal numbers, were of normal morphology and were in their usual mid-epidermal position. These observations do not support the hypothesis that LCs are involved directly in the process of keratinization.

Cell Count↗

Risk prediction after myocardial infarction. Comparison of three multivariate methodologies.

We predicted 30-day mortality and survival following acute myocardial infarction in two different hospital populations utilizing several multivariate statistical methodologies [linear discriminant analysis (LDA), logistic regression (LR), recursive partitioning (RP), and nearest neighbor]. Variables used were identified as predictive univariately from the base hospital and were obtained during the first 24 h after admission. LDA, LR, or RP all performed similarly within a given population; although each used the information contained in the prognostic variables differently. Application between different populations of prediction schemes based on LDA and LR was shown to be feasible but prior validation is essential.

Aged↗

Sustained regional dysfunction produced by prolonged coronary stenosis: gradual recovery after reperfusion.

Prolonged nontransmural ischemia was produced and the early and late effects of reperfusion were studied in 10 conscious dogs instrumented over the long term. Five hours of partial circumflex coronary artery stenosis was produced with a hydraulic occluder, followed by gradual release over 20 min, with measurements of left ventricular pressure, regional myocardial function (systolic wall thickening by sonomicrometry), coronary blood flow velocity (pulsed Doppler), and myocardial blood flow (microspheres). During coronary stenosis the occluder was adjusted frequently to maintain a reduction of systolic wall thickening to 50% to 75% of control (average 62.6% of control). Myocardial blood flow in the ischemic area at 4 hr of partial coronary stenosis was reduced in the inner layers of the myocardium (subendocardium, from 0.81 +/- 0.18 at control to 0.36 +/- 0.08 SD, p less than .01; midwall, from 0.77 +/- 0.20 to 0.46 +/- 0.07 ml/min/g, p less than .01), accompanied by significant ST segment elevation on the subendocardial electrogram (0.83 +/- 0.96 to 4.58 +/- 4.10 mV; p less than .05) and decreased left ventricular dP/dt (3503 +/- 462 to 2991 +/- 339 mm Hg/sec; p less than .01). Within a few minutes after complete release of partial coronary stenosis, ST segments returned to control and myocardial blood flow of the inner layers was increased (subendocardium, 1.37 +/- 0.39, p less than .01; midwall, 0.97 +/- 0.28, p less than .05), but systolic wall thickening and left ventricular dP/dt were significantly depressed and remained reduced at 24, 48, and 72 hr when myocardial blood flow was normal. By seven days, systolic wall thickening and left ventricular dP/dt had returned to control (94.1 +/- 7.0% of control, 3353 +/- 605 mm Hg/sec, respectively; NS). Histologic changes caused by ischemia constituted only 2.7% (average) of the tissue between the crystals in the ischemic wall, but ischemic damage in the posterior papillary muscle, which did not contain crystals, was 31.9%. Thus, regional myocardial dysfunction reduced by nontransmural ischemia for 5 hr persisted for at least 3 days, with only slight damage to the left ventricular free wall but considerable infarction of the posterior papillary muscle. Full recovery of regional and global contractile function of the free wall then occurred within a period of 1 week.

Animals↗

Effect of exercise on the relationship between myocardial blood flow and systolic wall thickening in dogs with acute coronary stenosis.

Relationships between regional myocardial perfusion and transmural function, both during treadmill exercise and at rest, were examined in conscious dogs with varying degrees of coronary stenosis produced by a hydraulic occluder. In 13 dogs we measured myocardial blood flow with microspheres (10-12 microns in diameter) and regional systolic wall thickening (%). During exercise with coronary stenosis, myocardial blood flow was characterized by nonuniform distribution, and associated with regional dysfunction. The relationships between normalized myocardial blood flow and normalized %wall thickening during exercise with coronary stenosis were linear, with significantly different slopes (mean myocardial blood flow: y = 1.23x - 0.16, r = 0.93; subendocardial myocardial blood flow: y = 1.50x - 0.02, r = 0.86; subepicardial myocardial blood flow: y = 0.83x - 0.18, r = 0.87). To fill the gap between available subendocardial and subepicardial data during exercise with coronary stenosis and control points, however, would require nonlinear components. In 10 of the dogs, coronary stenosis at rest was also produced to compare regional myocardial blood flow - %wall thickening relations at rest with those during steady state exercise. The absolute mean myocardial blood flow - %wall thickening relation during exercise with coronary stenosis (y = 11.6x - 1.9, r = 0.90) was significantly shifted rightward from the resting relation (y = 25.3x -2.1, r = 0.80). However, when changes in %wall thickening were plotted vs. myocardial blood flow per beat, the relationships at rest and exercise were nearly superimposable. Likewise, relations between normalized myocardial blood flow and changes in %wall thickening at rest and exercise were not significantly different. We conclude: %wall thickening during exercise is directly related to changes in mean myocardial blood flow but is related in nonlinear fashion to changes in subepicardial and subendocardial myocardial blood flow; %wall thickening may provide a reliable index of the relative transmural flow distribution during exercise as well as at rest; during brief bouts (5-8 minutes) of exercise with coronary stenosis, the relationship between stabilized regional contractile dysfunction and level of myocardial blood flow per beat is the same as that during coronary stenosis at rest.

Acute Disease↗

Future directions for clinical investigation in thrombolytic therapy.

Experiments in animals have shown that coronary artery reperfusion limits the extent of myocardial damage and brings about late return of regional contraction and overall left ventricular function over a period of several weeks. Such studies provide a basis for optimism that similar effects can be demonstrated after thrombolytic treatment in man, and such functional contractile recovery should provide an important end point in clinical investigations. However, before the initiation of a large-scale clinical trial, adequate methods for determining salvage of myocardium must be identified, and since changes in such measures may be small, the use of mortality as an end point should also be considered. In addition, the possibility of having two treatment groups to compare intracoronary and intravenous modes of therapy should be examined. Based on the growing number of uncontrolled clinical reports concerned with the success of intracoronary thrombolysis in restoring vessel patency and preliminary data on morbidity, mortality and potential improvement in left ventricular function with this procedure, planning for a randomized clinical trial sponsored by the National Institutes of Health is warranted.

Animals↗

mRNA-deficient beta o-thalassemia results from a single nucleotide deletion.

The beta-globin gene of a patient with mRNA-deficient beta o-thalassemia has been sequenced. We find a single nucleotide deletion in amino acid codon 44 that produces a UGA terminator at codon 60. We have previously shown that the beta-globin mRNA of this patient is correctly spliced and polyadenylated, but rapidly turns over with a half-life of less than 30 min. We suggest that the rapid mRNA turnover is influenced by the deletion of this single nucleotide as well as by the nonsense codon.

Adolescent↗

Simultaneous presentation of carcinoma involving the ovary and the uterine corpus.

Twenty-nine patients had simultaneous malignant epithelial neoplasms of the uterine corpus and ovary. Three groups were defined on the basis of tumor histology: Group A: those with endometrioid carcinoma in both the uterus and ovary; Group B: those with special variants of corpus carcinoma (papillary, clear cell, mucinous) and identical neoplasms in the ovary; and Group C: those whose uterine and ovarian carcinomas were of dissimilar histologic types. Sixteen women had endometrioid carcinoma in both sites. The median age at diagnosis, 41 years, was younger than is usual for corpus or ovarian cancer. For all 16 patients, the grade of the ovarian endometrioid carcinoma was similar to that of the endometrioid carcinoma of the uterine corpus. Seven patients had bilateral ovarian neoplasms. Only one patient had myometrial invasion by the corpus carcinoma. No patient with simultaneous ovarian and uterine endometrioid carcinoma, regardless of grade, has died of cancer although one vaginal relapse was treated successfully. This excellent survival of patients with simultaneous endometrioid carcinomas is better than would be expected for either Stage III adenocarcinoma of the endometrium or Stage II ovarian carcinoma. These simultaneously occurring endometrioid neoplasms of ovary and endometrium are considered to be separate primary tumors. The morphologic reasons for this view and therapeutic implications are discussed. In contrast to the patients with endometrioid carcinoma, the eleven patients with other histologic types of carcinoma in the ovary and corpus were older (median age, 61 years) and more often postmenopausal (90%). These neoplasms were more aggressive, with frequent deep myometrial involvement (63%), tubal involvement (27%), and extension to other pelvic tissues (36%) at the time of initial diagnosis. Six of these 11 patients succumbed to their cancer despite surgical therapy and radiation. The distribution of tumor in some of these patients with nonendometrioid types of carcinoma is suggestive of a single primary with metastases. The therapeutic implications of these findings are discussed.

Adenocarcinoma↗

Crithidia fasciculata: a catalase-containing trypanosomatid sensitive to nitroheterocyclic drugs.

Crithidia fasciculata, which contains high levels of a cytosolic catalase, is sensitive to inhibition by at least two nitroheterocyclic drugs, Nifurtimox and MK 436, both of which are also active against Trypanosoma cruzi. Drug sensitivity is not enhanced in organisms containing reduced levels of catalase. The ultrastructural lesions in T. cruzi produced by nitroheterocycles, especially the swelling and gross vacuolation of the mitochondria, are seen also in C. fasciculata. These results are not consistent with the hypothesis that the action of drugs such as Nifurtimox on T. cruzi involve hydrogen peroxide accumulation as a result of the absence of catalase.

Animals↗

Contrast sensitivity at high velocities.

Measurements were made of the contrast required to see the direction of motion of drifting gratings (Part 1) and of moving bars (Part 2). The spatial frequency at which least contrast is required to see sinusoidal gratings decreases as their velocity increases, but peak sensitivity is identical at all velocities up to 800 deg/sec. Similarly, the wider a single bar, the higher the velocity at which it is best visible. A bar 80 deg wide is best seen when moving at 300-500 deg/sec, and can be seen, and its direction of motion identified, even when moving at 10(4) deg/sec. These results show that motion does not diminish the visual passband, but instead slides the spatial frequency window along the spatial frequency scale, maintaining peak sensitivity at a temporal frequency of about 10 Hz (at photopic luminances).

Differential Threshold↗