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Biomedical subjects

S C Smith

Publications and source records attributed to S C Smith.

At least 199 records · Page 11Linked to original sources

Adaptation of rigid fixation to cranial flap replacement.

The use of titanium craniofacial plates and the principles of rigid fixation have been adapted to cranial flap replacement. The technique has been in use for more than 18 months with no complications related to the technique or implant. The advantages of using titanium screws and plates to achieve superior healing and cosmesis, as well as the reduction of postoperative artifacts on magnetic resonance imaging and computed tomographic scans, are of benefit to neurosurgical patients.

Bone Plates↗

Whole blood electrolyte assay using ChemPro 500. A comparison of assay performance with standard laboratory instruments.

The ChemPro 500 'near-the-patient' analyser, with ChemPro 'Ion Profile' sensor cards, was evaluated for the assay of pH, Ca2+, K+ and Na+ in whole blood samples from patients in the intensive care unit or during surgery for heart or major blood vessel disease, or for liver transplantation. Imprecisions estimated from replicate whole blood measurements were much greater for all four ions than even the least stringent of the generally accepted analytical goals, and much greater than those estimated using quality assurance materials. Comparisons of assayed values with those obtained using standard laboratory instruments showed significant constant and proportional biases. The performance of the ChemPro 500 with the Ion Profile cards gave us no confidence in recommending their use to anaesthetists and intensivists.

Biosensing Techniques↗

Heart development in normal and cardiac-lethal mutant axolotls: a model for the control of vertebrate cardiogenesis.

The mechanisms which regulate myocardial differentiation are poorly understood. The cardiac-lethal (c) mutant of Ambystoma mexicanum, in which the heart never begins to beat, provides a valuable model system for studying this process. Using an in vitro assay, we examine the nature of the defect in c/c embryos and find (contrary to previous reports) that the inductive endoderm is not affected by the mutation. Rather, the pre-cardiac mesoderm is directly affected by the c gene and is incapable of responding to normal inductive influences. Furthermore, we find that mutant mesoderm can complete its differentiation into functional cardiomyocytes when co-cultured with wild-type heart mesoderm. With this evidence, we propose a model for the regulation of heart differentiation based on the migration of the heart mesoderm over a gradient of inducer, and the subsequent establishment of a two-component reaction-diffusion system within the mesoderm itself. This model has the potential to explain several poorly understood aspects of cardiogenesis, including the gradual nature of heart induction, the restriction of the heart field, and possibly the early morphogenesis of the heart tube.

Ambystoma mexicanum↗

Trends in use of coronary angiography in subacute phase of myocardial infarction.

BACKGROUND: Most patients do not undergo acute reperfusion after myocardial infarction, and which of these patients should undergo coronary angiography is still debated. METHODS AND RESULTS: We analyzed the 1-year clinical outcomes and rates of coronary angiography performed as late as 60 days after myocardial infarction in 3,804 patients admitted between 1979 and 1988 and followed in six different centers. Patients less than 75 years old were classified into low-, medium-, and high-risk groups using a multivariate analysis of historical and clinical variables gathered during the first 8 hospital days. Patients who underwent early reperfusion (17%, all after 1984) were analyzed separately. To analyze time trends, patients were compared before and after mid-1984. Mortalities from day 9 through 1 year were similar for the two time periods in the low- (3.3% versus 2.5%) and medium-risk (7.4% versus 5.6%) groups, but mortality was lower for the high-risk group after 1984 (31.6% versus 20.0%). The proportion of patients undergoing coronary angiography increased dramatically in each group after 1984 (low risk, 18% versus 48%; medium risk, 23% versus 49%; high risk, 10% versus 32%, before and after 1984, respectively). Furthermore, a large percentage of patients (more than 40%) in the low-risk group did not have at least one of the indications for coronary angiography recently recommended by a joint task force. Among patients undergoing coronary angiography, the proportion of patients with three-vessel coronary artery disease decreased after 1984, whereas the proportion undergoing mechanical revascularization in the year after infarction increased in all risk groups. CONCLUSIONS: Despite the recent development of noninvasive techniques with high sensitivity for detecting high-risk patients after myocardial infarction, coronary angiography is being performed increasingly in all patients, including those determined to be at low risk for complications based on clinical data. The economic consequences of such a trend could be considerable, and its impact requires careful analysis.

Age Factors↗

Right and left ventricular function after cardiac transplantation. Changes during and after rejection.

BACKGROUND: Attempts to identify noninvasive markers of ventricular dysfunction accompanying acute rejection have been hampered by a lack of detailed simultaneous hemodynamic data. Therefore, we prospectively performed serial monitoring of detailed left and right heart hemodynamic parameters in cardiac transplant recipients at the time of routine endomyocardial biopsy to better define the physiology of the allograft heart during and after acute rejection. METHODS AND RESULTS: To better assess the pathophysiology of the rejection process, 18 cardiac transplant patients were prospectively studied by serial right heart micromanometer catheterization and digital image processing at the time of routine endomyocardial biopsy. Eleven patients had 18 episodes of rejection. Studies of baseline (negative biopsy preceding rejection), rejection (acute moderate rejection), and resolved (first negative biopsy after rejection) states were compared. Seven patients who did not experience an episode of rejection served as the control group. Right ventricular minimum and end-diastolic pressures increased from baseline values of 0.9 +/- 3.2 and 6.9 +/- 3.7 mm Hg, respectively, to 3.2 +/- 5.5 and 9.9 +/- 6.6 mm Hg, respectively, with rejection (both variables, p less than 0.05) and remained elevated despite histological resolution of rejection (4.3 +/- 5.5 and 10.0 +/- 7.1 mm Hg, respectively; p less than 0.05 for both variables compared with baseline values). Concurrently, right ventricular end-diastolic volumes (133 +/- 29, 119 +/- 27, and 114 +/- 30 ml; baseline, rejection, and resolved, respectively) and left ventricular end-diastolic volumes (133 +/- 24, 117 +/- 20, and 113 +/- 30 ml; baseline, rejection, and resolved, respectively) significantly decreased during rejection and remained decreased after resolution of rejection (rejection and resolved compared with baseline values, p less than 0.05). Right ventricular chamber stiffness (0.055 +/- 0.035, 0.085 +/- 0.057, and 0.092 +/- 0.076 mm Hg/ml; baseline, rejection, and resolution, respectively; rejection and resolved compared with baseline values, p less than 0.05) increased with rejection and remained elevated after resolution of rejection. Right ventricular peak filling rate also increased from a baseline value of 2.48 +/- 0.45 to 2.76 +/- 0.63 ml end-diastolic volumes per second with rejection (p less than 0.05). Elevation of right ventricular filling pressures, peak filling rate, and chamber stiffness with a concomitant decrease in end-diastolic volume is consistent with a restrictive/constrictive physiology. Mean arterial blood pressure and systemic vascular resistance were elevated after the resolution of rejection (compared with either rejection or baseline values, p less than 0.05) associated with a higher mean daily dose of prednisone (resolved compared with either baseline or rejection values, p less than 0.05). The control group experienced a time-dependent increase in mean and diastolic systemic arterial pressures (both comparisons, p less than 0.05) without detectable diastolic dysfunction. CONCLUSIONS: Persistence of biventricular diastolic dysfunction may be due to an irreversible effect of rejection, although multifactorial changes in left ventricular afterload occur that may complicate serial assessment of ventricular function.

Adult↗

A restriction fragment length polymorphism in the pigeon pro alpha 2(1) collagen gene: lack of an allelic association with an atherogenic phenotype in pigeons genetically susceptible to the development of spontaneous atherosclerosis.

A high frequency restriction fragment length polymorphism (RFLP) at the 3'-end of the pigeon pro alpha 2(1) collagen gene was detected using the restriction endonuclease EcoR1. The distribution of this allelic variant was analyzed in DNA isolated from White Carneau pigeons genetically susceptible to the development of spontaneous atherosclerosis. The atherogenic phenotype in individual pigeons was measured by the determination of total cholesterol and cholesterol ester levels in the celiac focus of the thoracic aorta of adult White Carneau pigeons. Aortic wall cholesterol levels correlated with an increase in lesion size. No correlation, however, was observed between allelic variants of the pigeon pro alpha 2(1) collagen gene and the atherogenic phenotype in White Carneau pigeons suggesting lack of linkage between this allelic marker and the genetic susceptibility to spontaneous atherogenesis. This is the first study of its kind in this animal model and serves to provide a basis for the further analysis of co-segregation of RFLPS in candidate genes to this polygenic phenotype.

Animals↗

The effect of exercise on plasma lipids and LDL subclass metabolism in miniature swine.

The effects of exercise on plasma lipids and lipoproteins, high density lipoprotein (HDL) subclass cholesterol levels, and low density lipoprotein (LDL) subclass composition and metabolism were studied in Yucatan miniature swine following 2 yr of training. The exercise protocol produced significant training effects. Post-heparin lipolytic activity was also significantly increased. Although plasma cholesterol and triglycerides did not differ significantly (P = 0.08) between the exercised and control groups, multivariate analysis indicated a strong association between lipoprotein lipase (LPL) and HDL2-C (P less than 0.0001). Although HDL-C levels rose only slightly (P less than 0.09) with exercise, a significant shift was noted in the distribution of cholesterol from the HDL3 to the HDL2 fractions, perhaps mediated by the substantial increase in LPL activity. Exercise had little effect on the chemical composition of the major lipoprotein classes; however, the triglyceride content of the lighter LDL1 subclass was significantly reduced. In the more dense LDL2 subclass, exercise resulted in a significant decrease in triglycerides concomitant with a significant increase in free cholesterol levels. In contrast with the small reductions in fractional catabolic rates (FCR) in either subclass, production rates of the exercised group were reduced, which accounted for the reduction in LDL subclass pool size. These data indicate that exercise produces subtle but significant changes in lipoprotein metabolism that have been previously associated with reduced risk of atherosclerosis.

Animals↗

Fluorescence assay for per-cell estimation of cytochrome P-450-dependent monooxygenase activities in keratinocyte suspensions and cultures.

An assay was characterized that facilitated per-cell estimation of cytochrome P-450-dependent monooxygenase activities in whole-cell suspensions and cultures of murine epidermal keratinocytes (MEKs). 7-Ethoxycoumarin O-deethylase (7-ECD), 7-ethoxyresorufin O-deethylase (7-ERD), and 7-pentoxyresorufin O-deethylase (7-PRD) activities were monitored by fluorescent detection of their products. MEKs were made permeable by a freeze-thaw cycle, and xenobiotic metabolism occurred in situ. Analyses of cultured MEKs were made with the cells attached to the culture dishes. Product formation was proportional with MEK cell number and assay time and was dependent upon a NADPH-generating system. The three monooxygenase activities were inhibited to various degrees, in a dose-dependent manner, by the P-450 inhibitors alpha-naphthoflavone and metyrapone. The number of MEKs obtained from a single mouse was sufficient for multiple analyses. The assay was also used to determine monooxygenase activities in whole-cell suspensions of rat hepatocytes. Constitutive per hepatocyte 7-ECD, 7-PRD, and 7-ERD activities were 357-, 96-, and 1926-fold greater, respectively, than the activities measured in suspensions of dorsal MEKs.

7-Alkoxycoumarin O-Dealkylase↗

Heart induction in wild-type and cardiac mutant axolotls (Ambystoma mexicanum).

We have re-examined some of the factors affecting the induction of heart-forming mesoderm in the axolotl. The formation of functional, rhythmically contracting myocardial tissue was used as an assay. We have found that heart-forming mesoderm is fully induced and capable of completing its developmental repertoire by the end of neurulation. As has been previously reported, pharyngeal endoderm appears to be the major inductor of heart mesoderm. Unlike previous workers, we have found that the inducing activity appears to be highly localized in the mid-ventral pharyngeal endoderm. The endoderm retains its inductive properties, and the mesoderm retains at least some capacity to respond, long after the heart-forming mesoderm is apparently fully induced. We have also found that RNA extracts from pharyngeal endoderm, which are capable of causing cardiac-lethal (c/c) mutant axolotl hearts to begin beating, are not capable of inducing early wild-type heart-forming mesoderm. Based on these results, we speculate that induction of heart-forming mesoderm is a two-step process. The first signal, occurring during neurulation, directs the mesoderm to begin differentiating into cardiomyocytes, and the second, beginning in mid- to late neurulation and continuing until just prior to the onset of heartbeat, causes myofibrillogenesis and the initiation of rhythmic contractions. The latter signal, which is lacking in c/c mutant embryos, appears to be necessary to override an inhibition present in the embryonic milieu.

Ambystoma↗

Development of the mechanoreceptive lateral-line system in the axolotl: placode specification, guidance of migration, and the origin of neuromast polarity.

The mechanosensory lateral-line system offers a unique opportunity to study a wide variety of developmental phenomena, including cell migration, the origin of polarity, and pattern formation. In this study, we use a series of transplantation experiments to examine some of the factors affecting the origin of the lateral-line placodes, the establishment of sensory organ polarity and placement, and the guidance of cell migration in the Mexican axolotl (Ambystoma mexicanum). We find that placode-forming ectoderm is at least partially specified as early as the beginning of neurulation, and we suggest that this may be a result of early processes involved in neural induction. Furthermore, we find that the migration of the primordia on the body depends on the presence of both the ectoderm and the subjacent mesoderm for guidance. Sensory organ polarity on the body appears to be the result of an interaction between the primordia, which deposit organs of set polarity relative to the direction of migration, and the substrate, which determines the direction of migration. Spacing of the organs is independent of the substrate, and may be due to an intrinsic property of either the primordia or the emerging organs themselves. Finally, we suggest that the lateral-line primordia are guided, as they migrate, by a contact guidance mechanism.

Ambystoma↗

Improved patient survival after cardiac arrest using a cardiopulmonary support system.

A portable cardiopulmonary bypass system that can be rapidly deployed in a nonsurgical setting using nursing staff was used in 38 patients with cardiovascular collapse refractory to ACLS protocol. Percutaneous or cutdown cannulation sites were: femoral vein-femoral artery (n = 18), right internal jugular vein-femoral artery (n = 2), right atrium-ascending aorta (n = 12), or a combination approach (n = 4). Two patients could not be cannulated. Patient diagnoses were pulmonary emboli (n = 3), failed coronary angioplasty (n = 7), myocardial infarction with cardiogenic shock (n = 5), trauma (n = 7), aortic stenosis (n = 2), postcardiotomy deterioration (n = 10), deterioration after cardiac transplantation (n = 2), cardiomyopathy with shock (n = 1), and ruptured ascending aortic dissection (n = 1). Ninety-five percent of patients (36 of 38) were successfully resuscitated to a stable rhythm. Eight diagnostic procedures (coronary angiography, n = 4; pulmonary angiography, n = 3; and aortography, n = 1) were performed while patients were on cardiopulmonary support. Early deaths resulted from massive hemorrhage (n = 8), inability to cannulate (n = 2), and irreversible myocardial injury (n = 10). Sixty-six percent (24 of 36) of patients successfully cannulated underwent conversion to standard cardiopulmonary bypass with attendant operative procedure or placement of ventricular assist device or total artificial heart. Fifty percent (18 of 36) of patients cannulated were successfully weaned from cardiopulmonary support, and 17% (6/36) are long-term survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparative molecular properties of swine and human very low density lipoproteins-apoproteins E and C.

1. By means of 2-dimensional gradient-gel electrophoresis, the very low density lipoproteins (VLDL) apoproteins E and C profiles from human and swine plasma were studied. 2. The molecular properties (isoelectric point and molecular weight) of the VLDL apoproteins and their isoforms were determined and showed many similarities between species. 3. It also appears evident that a previously unrecognized apoprotein (C-III) and several associated isoforms may exist in swine; however, it's mobility on 2-dimensional gradient gels is very similar to Apo C-II.

Animals↗

Biochemical and immunochemical characterisation of strains of Treponema hyodysenteriae.

The protein composition of 18 clinical isolates of Treponema hyodysenteriae from pigs with swine dysentery in Australia were compared by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis. Coomassie Blue stained SDS-PAGE-profiles of whole cell and outer membrane (OM) proteins demonstrated the same gel pattern among the T. hyodysenteriae isolates, particularly the OM proteins in the molecular mass (Mr) range of 30 kDa to 40 kDa. The T. hyodysenteriae isolates were categorised into two distinct groups (A and B) based on the strain-variability in the 37 kDa OM protein. Immunoblotting of whole cell proteins after SDS-PAGE using serum from rabbits and pigs immunised with known T. hyodysenteriae serotypes revealed a number of common immunoreactive bands in all isolates. LPS typing of the T. hyodysenteriae isolates by immunoblotting with the rabbit antiserum revealed one additional serotype emphasising the LPS heterogeneity among the strains isolated from geographic locations in Australia, Great Britain and the U.S.A. Immunoblotting of the OM preparations revealed several common immunoreactive polypeptides corresponding to Mr values of 34 kDa to 30 kDa among the T. hyodysenteriae and T. innocens isolates but a distinct 39 kDa found only in the T. hyodysenteriae isolates. Trypsin proteolysis of intact. T. hyodysenteriae cells caused selective loss of these and other major abundant proteins identifying the location of the 39 kDa, 36 kDa, 34 kDa and 30 kDa proteins on the cell surface and suggesting a possible role of these proteins in the pathogenesis of swine dysentery.

Animals↗

Outlook after acute myocardial infarction in the very elderly compared with that in patients aged 65 to 75 years.

Little is known concerning late outcome and prognostic factors after acute myocardial infarction in the very elderly (greater than 75 years of age). Accordingly, this study compared the clinical course and mortality rate for up to 1 year in a large multicenter data base that included 702 patients greater than 75 years of age (mean +/- SD 81 +/- 4 years), with a less elderly subset of 1,321 patients between 65 and 75 years of age (mean 70 +/- 3 years). The postdischarge 1 year cardiac mortality rate was 17.6% for those greater than 75 years of age compared with 12.0% for patients between 65 and 75 years of age (p less than 0.01). There were differences in the prevalence of several factors, including female gender, history of angina pectoris, history of congestive heart failure, smoking habits and incidence of congestive heart failure during hospitalization. Multivariate analyses of predictors of cardiac death in hospital survivors selected different factors as important in the two age subgroups; age was selected in the 65 to 75 year age group but was not an independent predictor in the very elderly. The survival curves beginning at day 10 for patients 65 to 75 and in those greater than 75 years old were similar for up to 90 days but diverged later. In the very elderly, 63% of late cardiac deaths were sudden or due to new myocardial infarction, similar to the causes of 67% of deaths in the younger age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Changes in vascular extracellular matrix accumulation reflect phenotypic differences between the arterial wall of pigeons resistant and susceptible to the development of spontaneous atherosclerosis.

White Carneau pigeons have previously been shown to be genetically susceptible to the development of spontaneous atherogenesis. The severity of development of atheromatous lesions is considerably greater than a more resistant breed of Show Racer pigeons. Analysis of levels of total hydroxyproline and isodesmosine in the thoracic aorta and celiac bifurcation of prelesion, six-week-old White Carneau and Show Racer pigeons, revealed an increased accumulation of total collagen and cross-linked elastin in the White Carneau arterial tissue. Using dot blot hybridization, measurements of steady state levels of several mRNAs in total RNA extracted from pigeon aortic tissue were also determined. While the increased deposition of extracellular matrix proteins was paralleled by a significantly greater recovery of mRNAs coding for pro alpha 1(1) collagen and elastin, in RNA extracted from White Carneau aortal tissue, increased recovery of mRNAs coding for an intracellular protein, gamma-actin were also observed in White Carneau aortal tissue. No differences in steady state levels of mRNAs coding for pro alpha 1(1) collagen and elastin were observed in RNA extracted from pigeon liver, suggesting a tissue specific increase in the mRNAs coding for these connective tissue proteins in aorta. A markedly reduced cell population however, was responsible for this overall increase in biosynthetic activity in White Carneau pigeon aortic tissue. This was demonstrated by a reduced cell count and by the recovery of reduced levels of total DNA in the thoracic aorta and celiac bifurcation of the White Carneau pigeon. The cell population in White Carneau aortic tissue exhibits therefore a markedly different phenotype with respect to a capacity for the biosynthesis of extracellular and intracellular proteins.

Actins↗