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Biomedical subjects

R S Fraser

Publications and source records attributed to R S Fraser.

At least 37 records · Page 2Linked to original sources

Catheter-induced pulmonary artery perforation: pathologic and pathogenic features.

Perforation of the pulmonary artery due to insertion of a balloon-tipped, flow-directed (Swan-Ganz) catheter is described in four cases. These cases were found in a consecutive series of 270 autopsies done over a 1.5-year period and suggest that the incidence of this complication may be greater than the number of clinically reported cases implies. In three instances, a focal parenchymal hematoma or thrombotic nodule identified the site of rupture. Other pathologic features and the pathogenesis of the perforation are discussed. Difficulties in postmortem diagnosis include distinguishing perforation from hemorrhage due to trauma, thromboembolism, and coagulation abnormalities.

Aged↗

Pulmonary involvement in giant cell arteritis.

While clinically suspected in some cases, pulmonary lesions in giant cell arteritis have rarely been described pathologically. We report the findings at autopsy in an elderly woman with typical giant cell arteritis. In addition to inflammation of temporal and other major systemic vessels, large- and medium-sized pulmonary arteries showed focal necrosis as well as medial granulomatous inflammation. These findings, as well as a review of previous clinical and pathologic reports, emphasize that the disease can affect the lungs and may rarely be a significant cause of morbidity.

Aged↗

A new physical assay method for tobacco mosaic virus using a radioactive virus recovery standard and the first derivative of the ultraviolet absorption spectrum.

A new physical assay method for tobacco mosaic virus is described which incorporates two improvements on previous procedures. Losses of up to 75% of virus during extraction are corrected by adding a trace of radioactive virus to leaf samples before homogenization, and determining percentage recovery of radioactivity in final virus preparations. Estimation of virus concentration in partially purified preparations is from the first derivative (dA/d lambda) of the ultraviolet absorption spectrum, using a pronounced signal from the tryptophan fine-structure absorption band at 285-293 nm. This method is highly insensitive to ultraviolet-absorbing contaminants, which cause errors and increase variation between replicates, when estimation of virus concentration is by normal measurement of ultraviolet absorption (A260). The method can be applied to at least some other viruses.

RNA, Viral↗

Long-term effects of pulmonary shrapnel injury. Report of a case with carcinoma and residual shrapnel tract.

Bullets and shrapnel fragments may occasionally lead to intrathoracic complications many years after their initial penetration. We report a case of pulmonary carcinoma arising in relation to pleural scarring from a shrapnel wound received 38 years earlier. An incidental finding was a patent, epithelialized tract running from the upper lobe pleural scar deep into the lower lobe, interpreted as a residue of the shrapnel's path through the lung.

Adenocarcinoma, Papillary↗

Theoretical analysis of a method for determining the pattern of macromolecular synthesis during the cell cycle.

The dual-labelling centrifugal-elutriation method has been extensively used to study patterns of macromolecular synthesis and accumulation in the yeast cell cycle. Cells are long-term labelled with a radioactive precursor for about 1.5 cycles (a measure of macromolecular mass), then pulse-labelled with a precursor containing a different radioactive isotope for the final 0.1 cycle (a measure of rate of synthesis). Harvested cells are fractionated into cell cycle stages by centrifugal elutriation, and changes in pulse : long-term labelling during the cycle determined. This pattern of change is compared with theoretical changes in rate : mass calculated for various patterns of synthesis. Using this method, it has been suggested that rates of synthesis and accumulation of several types of RNA and protein all increase exponentially through the cycle. In contrast, experiments using synchronous cultures or zonal centrifugation for cell cycle analysis have suggested other synthetic patterns, including periodic doubling in rate in each cycle. In this paper we analyse whether the dual-labelling, centrifugal-elutriation method is capable of discriminating between exponential and periodic rate-doubling patterns. Three possible sources of imprecision in the method and its application are examined. (1) Theoretical rate : mass curves have been simulated for macromolecules with a wider range of properties than previously considered. It is shown that for some important classes, such as messenger RNAs, with turnover rates in the range measured experimentally, and proteins, differences between rate : mass curves for exponential and periodic rate-doubling models are considerably smaller than previously suggested. (2) Long-term labelling is shown to be an accurate measure of macromolecular mass, but pulse-labelling can be inadequate as a measure of rate of synthesis. The error is greater with RNAs with faster turnover, and again reduces the ability of the method to discriminate exponential and periodic rate-doubling models of synthesis. The error is greater with RNAs with faster turnover, and again reduces the ability of the method to discriminate exponential and periodic rate-doubling models of synthesis. (3) Imperfections in cell cycle fractionation by centrifugal elutriation are examined, and by computer simulation it is shown that these also reduce the ability of the method to distinguish between the two models of synthesis. The three sources of imprecision are cumulative. It is concluded from simulation analyses that the differences between exponential and periodic rate-doubling patterns analysed by the method would be so small as to be almost impossible to establish against the background of error in experimental measurement. We therefore suggest that in practice, the dual-labelling centrifugal-elutriation method is unable to discriminate between the exponentially increasing and periodic rate-doubling models. The mathematical treatment developed in this paper should be applicable to analysis of other methods and cell cycle events.

Cell Cycle↗

Infective endocarditis: surgical treatment of 41 patients.

Forty-one patients with infective endocarditis were treated surgically at the University of Alberta Hospital, Edmonton, between 1961 and 1980. Their ages ranged from 10 to 67 years and the male to female ratio was 4:1. A wide variety of organisms were cultured but gram-positive organisms predominated. Bicuspid aortic valves, normal valves and valves affected by rheumatic heart disease, were the most common sites of infection. The aortic valve was most frequently involved. The onset of left ventricular failure was the major indication for surgery. The overall mortality at 30 days was 19.5%. The mortality after 30 days was 9.8%. Eleven of 12 patients who died had left ventricular failure preoperatively. The mortality in patients who had valve replacement during the first 4 weeks of infection did not differ from those who had valve replacement after 4 weeks of infection. Hemodynamic studies following operation in six patients showed that pulmonary arterial and wedge pressures had returned to normal levels. Nineteen of 26 patients who were followed up were asymptomatic. One had a malfunctioning prosthesis, one chronic heart failure and one had reoperation for paravalvular leak. Four patients diet during the follow-up period. The authors conclude that all patients with infective endocarditis who suffer left ventricular failure should have prompt valve replacement regardless of the duration of antibiotic therapy.

Adolescent↗

Scoring technique for diagnosis of ventricular hypertrophy from three orthogonal lead electrocardiogram.

A prospective study for the development of scoring techniques for the diagnosis of ventricular hypertrophy from the three orthogonal lead electrocardiogram was undertaken. A total of 51 hearts was examined at necropsy in a training group on which the scoring techniques were developed and a test group of a further 82 hearts was studied to assess the sensitivity and specificity of the method. The hearts were classified as being normal or having left ventricular hypertrophy, right ventricular hypertrophy, biventricular hypertrophy, or were placed in a borderline category. These classifications were based on the measurement of the weight of the left ventricular free wall, the interventricular septum, and the right ventricular free wall. Classical electrocardiographic variables were selected and assigned a point score on the basis of their diagnostic value. The electrocardiographic diagnosis of left ventricular hypertrophy, right ventricular hypertrophy, and biventricular hypertrophy was then made when the relevant score exceeded four points. After excluding 25 cases which showed conduction defects or were regarded as borderline at necropsy, 57 cases remained in the test group for assessing the technique. The sensitivity and specificity for left ventricular hypertrophy were 65 per cent and 91 per cent, respectively. For right ventricular hypertrophy corresponding results were 53 and 90 per cent. For biventricular hypertrophy the sensitivity was lower at 42 per cent, with a corresponding specificity of 93 per cent. These results represent a considerable improvement over older techniques, with up to a tenfold increase in sensitivity being obtained. The technique can be applied with or without computer assistance.

Adult↗

Cardiac tamponade as a presentation of extracardiac malignancy.

Three cases of adenocarcinoma of the lung manifesting as acute pericardial effusion with tamponade are presented and the medical literature concerning this unusual manifestation of extracardiac malignancy is reviewed. We have found 22 cases of carcinoma and 4 cases of sarcoma. Of the carcinomas, 14 of 19 (74%) with known primary are pulmonary and 13 of 18 (72%) with tissue diagnosis are adenocarcinomas. Daignosis was made by cytologic examination of pericardial fluid in 14 of 16 cases (87%) in which it was performed. The lymphatic drainage of the heart renders some anatomical explanations for the prevalence of carcinoma of the lung as the cause of cardiac tamponade and the discrepancy of finding tumor cells in the pericardial fluid but not in the pericardium. Patients treated with pericardiectomy with or without ancillary radio- or chemotherapy survived longer than those treated with periocardiocentesis or radio- or chemotherapy alone.

Adenocarcinoma↗

Altered patterns of ribonucleic acid synthesis during the cell cycle: a mechanism compensating for variation in gene concentration.

In the fission yeast Schizosaccharomyces pombe, a series of diploid mutants divides at smaller cell sizes than wild type. In these smaller strains, the mean gene concentration (defined by previous authors as the DNA to protein ratio) is higher than in wild type. Such an increase in gene concentration should also increase the concentration of those components such as messenger and ribosomal RNA, whose rate of synthesis is determined by gene dosage. We show that the mean concentrations of these 2 RNA species in the small cells are not increased, but are the same as in wild type. The small mutant cells are thus able to compensate for changes in gene concentration. This compensation is shown to operate through differences in the patterns of synthesis of RNA during the cell cycle. In all the strains of the diploid series, the rates of synthesis of messenger and ribosomal RNA double as steps once in each cell cycle. The timings of the steps in the cell cycle appear to be cell-size related, since the smaller the cell at division, the later are the steps in the cell cycle. In contrast, there is comparatively little variation in the timing of DNA replication in the cycles of cells of different sizes. We propose that after DNA replication, there is a delay before doubling in the rate of transcription. Such a cell mass-related delay is all that is required to compensate for increased gene concentration, and results in the same mean functional DNA concentration in all strains. This mechanism will maintain the same mean messenger and ribosomal RNA concentrations in cells dividing at different sizes. Ways in which the cell size-related control over transcription may operate are discussed.

Adenine↗

Analysis of the significance of a periodic, cell size-controlled doubling in rates of macromolecular synthesis for the control of balanced exponential growth of fission yeast cells.

Mutant strains of the fission yeast Schizosaccharomyces pombe are available which divide at smaller mean sizes than wild type. Earlier work by the present authors has shown that all these strains double their rates of polyadenylated messenger RNA synthesis as a step once in each cell cycle. The smaller the cell, the later in the cycle is the doubling in rate of synthesis. Strains of all sizes, however, double their synthetic rate when at the same threshold size. We show here that the differences in cell cycle stage of doubling in rate of polyadenylated messenger RNA synthesis are enough to explain the reduced mean steady state polyadenylated messenger RNA contents of the smaller strains. The cell size-related control over doubling in rate of synthesis is also shown to maintain the mean polyadenylated messenger RNA content as a constant proportion of cell mass, irrespective of cell size. This control thus allows cells to maintain balanced exponential growth, even when absolute growth rate per cell is altered by mutation. It is also shown that the concentration of polyadenylated messenger RNA itself could act as a monitor of the threshold size triggering the doubling in rate of synthesis in each cell cycle.

Ascomycota↗

The effect of cell mass on the cell cycle timing and duration of S-phase in fission yeast.

Two isotopic methods for measuring DNA replication in the fission yeast Schizosaccharomyces pombe are described. The first is a method for measuring the total quantity of [3H]uracil incorporated into DNA after pulse labelling. The second is a means of detecting DNA replication in single cells by autoradiography. Both of these techniques have been used to investigate the timing and duration of S-phase in a series of mutant strains whose cell mass at division varies over a 3-fold range. The results support the hypothesis that in S. pombe there are 2 different controls over the timing of S-phase: an attainment of a critical cell mass and a dependency upon the completion of the previous mitosis coupled with a short minimum time in G1. Strains whose cell mass at birth is above this critical level initiate DNA replication almost immediately after septation, that is, very soon after the previous mitosis. Strains whose cell mass at birth is below the critical level do not initiate replication until the critical cell mass is attained. The duration of S-phase has been estimated from the proportion of cells whose nuclei are labelled after a pulse of given duration. S-phase is short in S. pombe, lasting only about 0.1 of a cell cycle in wild type. Cell mass at S-phase does not have any consistent effect on this length. We have also investigated the degree of synchrony of S-phase initiation in daughter cells, and have found that, in a cell cycle 240 min long, their S-phases are initiated within 1--2 min of each other. This result indicates that between sisters variability in the duration of the G1 phase is small compared with variability in the total cell cycle time, and argues against the hypothesis that the rate of cell cycle traverse is determined by a random transition in G1.

Ascomycota↗

Novel cell cycle control of RNA synthesis in yeast.

During the fission yeast cell cycle, the rate of polyadenylated messenger RNA synthesis doubles when the cell reaches a critical size. This size-related control maintains average mRNA content in balance with total cell mass during exponential growth, even in cells growing at different absolute growth rates per cell.

Ascomycota↗

Conjugation of coxsackievirus type B1-B6 immunoglobulins with fluorescein isothiocyanate by a "reversed" dialysis method.

Immunoglobulins from antisera to coxsackievirus B types 1--6 were labeled with fluorescein isothiocyanate by a "reverse" dialysis method of conjugation. Conjugates thus obtained were labeled at reproducible ratios of fluorescein to protein with weight-weight ratios ranging from 5.0 to 7.1 and estimated molar ratios ranging from 2.1 to 2.9. Conjugates were tested on cover-slip HeLa cell cultures by the direct method of staining. Two types of specific immunofluorescence were observed: intensely fluorescent perinuclear masses and discrete foci of bright fluorescence scattered throughout the cytoplasm. Titers of homotypic conjugates varied from 1:40 to 1:160. Heterotypic staining, consisting of a diffused hazy fluorescence, was observed only at the highest concentrations of conjugate and not above the 1:10 dilution. This technique proved to be specific and sensitive for the detection of group B coxsackievirus antigens in HeLa cells but failed in specific detection of the same antigens in samples of the myocardium obtained by biopsy of three patients clinically ill with idiopathic myocarditis.

Antibodies, Viral↗

Hypothermic coronary perfusion for myocardial protection during aortocoronary bypass.

Numerous methods have been used in an attempt to prevent myocardial injury that results from the interruption of aortic flow during cardiac operations. The authors describe a relatively simple means of inducing cardioplegia during coronary bypass surgery by coronary perfusion with cold lactated Ringer's solution through the aortic root. When the results following the employment of hypothermic coronary perfusion for intraoperative cardioplegia were compared with those obtained without its use, the procedure was found to confer a degree of intraoperative myocardial protection and appeared to lead to a decrease in intraoperative myocardial infarction, subendocardial ischemia and intraoperative mortality.

Coronary Artery Bypass↗

Myocardial protection during aortic valve replacement: normothermia versus hypothermia.

The operative results in 32 patients who underwent aortic valve replacement with aortic occlusion and normothermic myocardium (group 1) were compared with 54 similar patients in whom the myocardium was protected by hypothermic coronary perfusion through the aortic root (group 2). The operative mortality and the incidence of heart failure, subendocardial ischemia and myocardial infarction were the same in the two groups. The maximal concentrations of cardiac enzymes after operation in group 2 patients were significantly lower than those in group 1. The postoperative cardiac performance was significantly different in that only 5.6% of group 2 patients required inotropic agents after operation compared with 25% of group 1 patients. The patients in group 2 were easier to defibrillate after cardiopulmonary bypass.

Adult↗

Long-term survival after tricuspid valve replacement. Results with seven different prostheses.

The experience with tricuspid valve replacement (TVR) with seven different prostheses, alone or combined with replacement of other valves, in 73 patients (64 rheumatic and nine nonrheumatic) between 1964 and March, 1975, at the University of Alberta Hospital has been reviewed. Early and late mortality rates in rheumatic patients were 41 and 23 percent, respectively (36 percent being alive after a mean of 5.6 years), compared to 33 and 11 percent, respectively, in the nonrheumatic patients (56 percent being alive after a mean of 2 years). Of all survivors, 88 percent were functionally improved. Among the rheumatic patients: (1) 88 percent had organic tricuspid disease; (2) of the 39 patients with tricuspid insufficiency who underwent corrective mitral surgery 7 years before TVR, the tricuspid insufficiency had progressed over the 7 years; (3) the number of patients with tricuspid insufficiency had increased (39 versus 59) over the same 7 year period; (4) a high early mortality rate was encountered in those who were preoperatively in New York Heart Association (N.Y.H.A.) Class IV, or who had cardiomegaly, or pulmonary hypertension, or poor ventricular function, or organic disease, or reoperation; (5) the percentages of survivors with different prostheses were: Starr-Edwards, 31 percent; Beall-Surgitool, 14 percent; Kay-Shiley, 46 percent, Björk-Shiley, 50 percent; Lillehei-Kaster, 100 percent; Cutter-Smeloff and Wada-Cutter, nil. Among the nonrheumatic patients, two with the Cutter-Smeloff, two with the Beall-Surgitool, and one with the Lillehei-Kaster were alive after 14, 37, and 15 months, respectively. Among all survivors of TVR, late thrombus and pannus developed on both ball and disc prostheses (Starr-Edwards, two; Cutter-Smeloff, one; Lillehei-Kaster, one). These findings suggest that TVR should be performed earlier in rheumatic patients to reduce the operative mortality rate and that the Lillehei-Kaster prosthesis is probably most suitable for TVR.

Adolescent↗

Coarctation of the aorta in adults.

Thirty-six patients, 19 men and 17 women, presented at age 18 or older between 1952 and 1974 with coarctation of the aorta. Of the 14 (39%) who had associated cardiovascular disease, 12 had aortic stenosis or insufficiency or both. Three patients had infections-two, endocarditis (aortic valve) and one, endarteritis. Three of the seven patients who did not undergo an operation are alive, two at more than 50 years of age. Five patients had myocardial infarctions, two at 35 years of age. Twenty-nine (80%) had operations; in eight instances the patient was over age 40. All 18 patients undergoing repair of isolated coarctation survived, while only 7 of the 11 patients with associated cardiovascular lesions who underwent repair recovered. Aortic valvular disease and myocardial infarction are serious complicating factors in coarctation of the aorta.

Adolescent↗