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Biomedical subjects

E E Smith

Publications and source records attributed to E E Smith.

At least 19 recordsLinked to original sources

Resternotomy for bleeding after cardiac operation: a marker for increased morbidity and mortality.

Over a 2-year period from January 1, 1992, to December 31, 1993, of 2,221 patients undergoing cardiac operations in our unit, 85 (3.8%) were reopened for the control of bleeding (9 patients more than once). The incidence of resternotomy in coronary cases was 2.3%, but resternotomy was more than three times as likely in valve cases (odds ratio, 3.4; 95% confidence interval, 2.1 to 5.4). Previous cardiac operation was more common among resternotomy patients than among the remainder (18% versus 9%, respectively; p = 0.018). An identifiable source of bleeding was found in 57 of the 85 patients (67%), but a concurrent coagulopathy was common (45 patients). Resternotomy patients, as a group, had higher preoperative risk scores (Parsonnet) than did the other patients (p < 0.0001), stayed longer in the intensive care unit (p < 0.0001), and had greater requirements for intraaortic balloon counterpulsation (14% versus 3%) and hemofiltration (9% versus 3%) (p < 0.0001 and p < 0.01, respectively). Nineteen resternotomy patients (22%) died in the hospital, a proportion significantly greater than the risk assigned to this group of patients preoperatively (12.8%) (p = 0.008). In contrast, the observed mortality for the other 2,136 patients (5.5%) was significantly less (8.3%) (p < 0.00006). Multiple forward stepwise logistic-regression analysis confirmed resternotomy for excessive bleeding after cardiac operation to be a significant independent predictor of a prolonged stay in the intensive care unit (p < 0.0001), the need for intraaortic balloon counterpulsation (p < 0.0001), and death (p < 0.0001).

Aged

AMPA antagonist LY293558 does not affect the severity of hypoxic-ischemic injury in newborn pigs.

BACKGROUND AND PURPOSE: LY293558 is a systemically active alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) excitatory amino acid antagonist. AMPA antagonists have shown promise in several adult hypoxic-ischemic brain injury models, and we wanted to see if this work could be extended to a newborn animal. METHODS: Seventy-six (beta error < .10) 0- to 3-day-old piglets under 1.5% isoflurane anesthesia underwent placement of carotid snares and arterial and venous catheters. While paralyzed with succinylcholine under 0.5% isoflurane, 50% nitrous oxide, piglets were randomly assigned to receive either 5 mg/kg or 15 mg/kg of LY293558 or saline at time--10 minutes and again 10 hours later. At time 0, both carotid arteries were clamped, and blood was withdrawn to reduce the blood pressure to two thirds of normal. At time 15 minutes, inspired oxygen was reduced to 6%. At time 30 minutes, the carotid snares were released, the withdrawn blood was reinfused, and the oxygen was switched to 100%. On the third day after the hypoxic-ischemic injury, the animals were killed by perfusion of the brain with 10% formalin. Brain pathology was scored by a blinded observer. RESULTS: There were no significant differences between the drug-treated and control groups. CONCLUSIONS: The systemically active AMPA antagonist LY293558, when given at a dose of 5 mg/kg or 15 mg/kg before injury and 10 hours later, does not affect the severity of hypoxic-ischemic brain injury in newborn piglets. Neither AMPA receptor activity nor NMDA receptor activity are important in brain injury in this model.

Animals

Emergence of mature teratoma following treatment of sacrococcygeal endodermal sinus tumor: CT and MR imaging with pathological correlation.

We report a case of pseudoretroconversion in which, clinically and pathologically, it appeared that an endodermal sinus tumor retroconverted to mature teratoma. An 8-month-old white female infant with a sacrococcygeal tumor, diagnosed by biopsy as endodermal sinus tumor (yolk sac tumor), was treated with chemotherapy. The residual tumor after treatment was mature teratoma confirmed by imaging and by pathological examination. We present the computerized tomography (CT) and magnetic resonance imaging (MRI) findings with pathological correlation.

Endodermal Sinus Tumor

Proximal and distal sites bind LuxR independently and activate expression of the Vibrio harveyi lux operon.

The LuxR regulatory protein of Vibrio harveyi as well as the autoinducer molecule, N-(3-hydroxybutanoyl) homoserine lactone, are known to be required for expression of luminescence. Although LuxR has been implicated in the activation of the promoter of the lux operon of V. harveyi, and can bind to two distinct sites upstream of the transcription initiation start site, its mode of action is unknown. In the present experiments, mobility shift assays were used to demonstrate that LuxR bound to the distal and proximal sites in an independent rather than co-operative interaction with a much tighter binding to the distal site. Deletion mutation analyses of DNA upstream of the lux promoter followed by transconjugation into V. harveyi in trans using the chloramphenicol acetyltransferase (cat) gene as a reporter demonstrated, however, that the proximal site for LuxR was absolutely critical for promoter activation while the distal LuxR site was only necessary for maximum activation. This result was confirmed by mutation of the proximal site which blocked activation of the lux promoter and binding of LuxR to this site, but did not prevent LuxR binding to the distal site.

Bacterial Proteins

Glucose given after hypoxic ischemia does not affect brain injury in piglets.

BACKGROUND AND PURPOSE: Giving glucose before hypoxic ischemia worsens brain injury in piglets. Does giving glucose after hypoxic ischemia affect severity of injury? METHODS: Forty-three 0- to 3-day-old pigs were used. All piglets received 2 U/kg insulin before injury to prevent stress-induced hyperglycemia. Hypoxic ischemic brain damage was induced by clamping both carotid arteries and reducing arterial blood pressure to two thirds of normal by hemorrhage at time 0. At 15 minutes the fraction of inspired oxygen (FIO2) was reduced to 6%. At 30 minutes FIO2 was increased to 100%, the carotids were released, and the withdrawn blood was reinfused. The piglets were then randomized to receive either 2 mL/kg of 50% dextrose followed by 2 mL/kg per hour for 2 hours or an equal volume of saline. RESULTS: Neurological examination scores (20 is normal, 5 is brain dead, by blinded observer) at 1 day postinjury were similar in the two groups: glucose, median 15.5 (25th percentile, 12.2; 75th percentile, 18); controls, 15.6 (9.3, 18). Piglets were killed at 3 days with brain preservation at death. Pathological examination scores (sum of scores from cortex, hippocampus, and basal ganglia: 30 is normal, 3 is total necrosis) by blinded observer were similar in the two groups: glucose, 26 (18, 28); controls, 25 (16.5, 28); NS. CONCLUSIONS: Although elevated glucose levels during hypoxic ischemic injury worsen brain injury in the piglet, elevated glucose levels after injury do not affect the severity of the injury.

Animals

Positional dyspnoea due to aneurysm of the thoracic aorta.

Thoracic aortic aneurysms may produce breathlessness by compressing the tracheobronchial tree. We report a patient whose shortness of breath demonstrated a marked positional component, due to varying compression of her major airways by the lesion.

Aged

Familial progressive subcortical gliosis.

We report clinical and pathologic findings from two kindreds afflicted with a familial form of progressive subcortical gliosis. The disorder segregated as an autosomal dominant trait. Onset was in the presenium and the course was slowly progressive. Affected individuals initially manifested personality change, degeneration of social ability, disinhibition, psychotic symptoms, memory impairment, or depression. Later, all developed progressive dementia, frequently associated with verbal stereotypy, decreased speech output, echolalia, or manifestations of the human Klüver-Bucy syndrome. Terminal clinical manifestations included profound dementia, frequently with mutism, dysphagia, and extrapyramidal signs. Autopsy of seven end-stage patients revealed generalized cerebral atrophy, predominantly involving the white matter of the frontal and temporal lobes. Microscopically, prominent fibrillary astrocytosis was present in the subcortical white matter and in the subpial and deep layers of the overlying cerebral cortex. These changes were most pronounced in the frontal and temporal lobes, especially in the cingulate gyri and insulae. Mild cortical neuronal loss accompanied the gliosis, but no myelin loss was evident. The claustra and substantia nigra also showed severe astrocytosis and degenerative changes. Amyloid deposits and neuronal cytoskeletal inclusions were absent.

Aged

Dietary hydrated sodium calcium aluminosilicate reduction of aflatoxin M1 residue in dairy goat milk and effects on milk production and components.

Lactating dairy goats were exposed to aflatoxin (100 and 200 ppb) and hydrated sodium calcium aluminosilicate at 1, 2, and 4% in two separate experiments. Naturally occurring low levels of aflatoxin M1 (.009 ppb) were found in the milk of the control diet, whereas there were no detectable levels of aflatoxin M1 in the milk of diets containing hydrated sodium calcium aluminosilicate in both experiments. In Exp. 1, no treatment-related differences in clinical behavior or significant difference in the feed intake, milk production, or milk component analyses were observed with 200 ppb of aflatoxin and 4% hydrated sodium calcium aluminosilicate. However, 4% hydrated sodium calcium aluminosilicate was responsible for an 86.9% reduction of aflatoxin M1 residue in the milk of diary goats. In Exp. 2, the combination of 1% hydrated sodium calcium aluminosilicate and aflatoxin at 100 ppb resulted in an overall reduction of aflatoxin M1 residue by 51.9%, which represented a mean change of aflatoxin M1 from .553 to .266 ppb of aflatoxin M1 in the milk. The diet that contained 2% hydrated sodium calcium aluminosilicate and 100 ppb of aflatoxin further reduced aflatoxin residue by a mean change from .553 to .098 of ppb aflatoxin M1, which represents an 82.2% reduction of aflatoxin M1 residue in the milk. Analysis of the data by time indicated that there were no statistical differences between days of sampling. Information regarding the ability of hydrated sodium calcium aluminosilicate to prevent or reduce the level of aflatoxin M1 residues in milk is critically needed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxin M1

Individual and combined toxicity of T-2 toxin and cyclopiazonic acid in broiler chicks.

The effects of feeding 6 mg T-2 toxin (T-2) and 34 mg cyclopiazonic acid (CPA)/kg of diet singly and in combination were characterized in male broiler chicks from 1 d to 3 wk of age. Body weights were depressed by T-2, CPA, and the combination of T-2 and CPA. There was a significant synergistic interaction between T-2 and CPA for relative liver and kidney weights and serum cholesterol and triglyceride concentrations and a significant interaction between T-2 and CPA for 3-wk body weights and relative bursa of Fabricius weights, which were less than additive. Neither the efficiency of feed utilization nor mortality was affected by dietary treatments. Oral lesions were present in a majority of the chicks fed diets containing T-2 with or without CPA. When compared with controls, other variables measured exhibited additive or less than additive toxicity. These data demonstrate that T-2 and CPA alone and in combination can cause reduced performance and adversely affect broiler health. The effects of these mycotoxins may be exacerbated by other factors when under field conditions; hence, the potential detrimental effects of these two mycotoxins when present alone or in combination cannot be dismissed.

Animals

Similarity- versus rule-based categorization.

An influential study by Rips (1989) provides the strongest evidence available that categorization cannot be reduced to similarity. In Rips's study, subjects were presented a sparse description of an object that mentioned only a value on a single dimension (e.g., "an object 3 inches in diameter"), followed by two categories (e.g., pizza and quarter), where one allowed more variability on the relevant dimension than did the other (the diameter of pizzas is more variable than that of quarters). Subjects judged the described object to be more likely to be a member of the variable category (pizza), but more similar to the nonvariable category (quarter). This dissociation between categorization and similarity strongly implies that categorization was not based on similarity. In our first experiment, we used sparse descriptions like Rips's, as well as rich descriptions that contained features characteristic of the nonvariable category. We found that categorization tracked similarity with both kinds of descriptions. In a second experiment, we modified our procedure to be more like that of Rips's by requiring subjects to think aloud while making their decisions. Now, like Rips, we found a dissociation between similarity and categorization with sparse items; with rich descriptions, categorization again tracked similarity. These findings are consistent with the hypothesis that categorization can be done in two ways, by similarity and by rule. An exclusive reliance on rule-based categorization seems to occur only when the description of the to-be-categorized object does not contain any features characteristic of any relevant category.

Adult

Effects of patulin on postimplantation rat embryos.

Patulin (PAT), a highly toxic, carcinogenic, heterocyclic lactone is produced by a variety of fungal species, including Penicillium and Aspergillus. This compound has been isolated from various apple products and is stable in apple and grape juice and dry corn. It has been reported to be cytotoxic and to exert adverse influence on development in vivo in mice and merits further study and evaluation. In this study, whole rate embryo culture (WEC) was used to determine the teratogenic potential of PAT in vitro. Embryos were exposed to PAT-treated (0.00-62 microM) rat serum for 45 h. The embryos that were exposed to 62 microM PAT were not evaluated because they did not survive beyond 40 h of incubation. The results indicate that PAT induced a statistically significant reduction in protein and DNA content, yolk sac diameter, crown rump length, and somite number count. Patulin treatment also resulted in an increase in the frequency of defective embryos. Anomalies included growth retardation, hypoplasia of the mesencephalon and telencephalon, and hyperplasia and/or blisters of the mandibular process. Thus, the data from the present study provide further evidence supporting the conclusion that the whole rat embryo assay is a rapid and sensitive in vitro method that can be employed to pre-screen developmentally toxic mycotoxins.

Animals

Ampliative inference: on choosing a probability distribution.

Ampliative inference is the choice of a probability distribution on the basis of incomplete information. We consider some psychological and normative questions that arise about this kind of reasoning. The discussion is largely tutorial although a substantive hypothesis is also advanced.

Decision Making

Characterization of detergent-soluble proteins of Corynebacterium pseudotuberculosis.

Whole cells and culture supernatant of isolates of Corynebacterium pseudotuberculosis were studied by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting (immunoblotting). SDS-PAGE analysis of detergent-solubilized whole cells revealed more than 20 bands in silver-stained gels. However, the SDS-soluble proteins that are present in all the isolates of the bacterium can be separated into four groups, as follows, (i) high molecular mass proteins that are greater than 119 kDa, (ii) a set of three proteins with molecular mass of 84, 64 and 58 kDa, (iii) a doublet consisting of proteins of molecular mass 33 to 30 kDa, and (iv) low molecular mass proteins of 25 to 20 kDa. SDS-PAGE analysis of ammonium sulphate concentrated culture supernatant demonstrated more than seven bands in silver-stained gels ranging in molecular mass from 64-14 kDa. Sera from goats with C. pseudotuberculosis-induced disease were used to probe immunoblots of electrophoresed SDS-soluble proteins. Ten or more SDS-soluble proteins from whole cells, ranging in molecular mass from 119-20 kDa were recognized by antibodies in sera of naturally infected goats. These sera also recognized up to five molecules ranging from 64-30 kDa, on immunoblots of ammonium sulfate concentrated culture supernatant.

Animals

Continuous 12-lead electrocardiograph monitoring in the emergency department.

Many patients presenting to the emergency department with suspected acute myocardial infarction have an initial electrocardiogram (ECG) non-diagnostic for acute injury or ischemia. Continuous ST segment monitoring devices have been used by physicians in the past to diagnose ischemia in the ambulatory outpatient population and to identify coronary occlusion in postthrombolytic and postsurgical patients. We report three patients with suspected acute myocardial infarction who underwent real-time continuous 12-lead ST segment monitoring with frequent serial ECGs on a microprocessor-controlled device during their initial emergency department evaluation. Continuous 12-lead ECG monitoring revealed significant changes on the ECG in all three cases presented, with a resultant change in emergency department therapy. Interestingly, all of these patients had significant ECG changes in the absence of recurrence of chest pain. We believe real-time continuous 12-lead ST segment monitoring with frequent serial ECGs can identify patients with an initially nondiagnostic or atypical ECG who may benefit from early interventional therapy.

Acute Disease

Disability and distress following cardiac surgery in patients over 70 years of age.

We have reviewed the outcome in a consecutive series of 254 patients over the age of 70 undergoing cardiac surgery between 1987-89. Of the patients, 62% were male and the median age was 73 years. Operations included: coronary bypass 57%, valve replacement 26%, combinations 14% and other procedures 3%. The hospital mortality was 7.5% and late mortality was 13.8%. Complications included: intraaortic balloon 6%, resternotomy for bleeding 4%, permanent pacing 3%, chest infection 14%, tracheostomy 5%, major cerebrovascular events 3% and minor 4%. Eighty-two percent left the intensive care unit within 24 h and 89% left hospital within 8 days. Two questionnaires (York University) were sent to 207 patients believed to be alive in order to evaluate the change in their quality of life following surgery. Of the 207 questionnaires 197 (95%) were returned, 7 of which were from relatives of patients who had died and 7 were incomplete. The responses of 183 assessable patients (at a mean follow-up of 36 months) were converted into Rosser disability (I-VIII) and distress (A-D) groups. There was a decrease in disability and distress in 60% and 67%, respectively, no change in 34% and 30% and deterioration in 6% and 3%. Cardiac surgery can be carried out in elderly patients with an acceptable early morbidity and mortality, and although many patients show sustained improvement in their quality of life, this was not demonstrated in about a third of patients. As the emphasis in the elderly should be on quality of life we ought to continue to concentrate on careful selection in this age group.

Aged

Use of polyethylene glycol-bound superoxide dismutase, polyethylene glycol-bound catalase, and nimodipine to prevent hypoxic ischemic injury to the brain of newborn pigs.

OBJECTIVE: To determine if polyethylene glycol-bound superoxide dismutase and catalase and nimodipine, alone or in combination, will ameliorate hypoxic ischemic injury to the brain. SUBJECTS: A total of 78 newborn (0 to 3 days) pigs were used. DESIGN: Prospective, blinded, randomized, controlled trial. INTERVENTIONS: The piglets were subjected to hypoxic ischemic brain injury. Carotid arteries were ligated at time 0 and BP was reduced one third by hemorrhage. At 15 mins, FIO2 was reduced to 0.6. At 30 mins, carotids were released, blood was reinfused, and FIO2 was increased to 1.0. Pigs were randomly assigned at time 35 mins to receive either: 10,000 U/kg of polyethylene glycol-bound superoxide dismutase and catalase (group 1); 0.5 mg/kg of nimodipine (group 2); both 10,000 U/kg of superoxide dismutase and catalase and 0.5 mg/kg of nimodipine (group 3); or no drugs (controls). MEASUREMENTS: The time after reoxygenation for return of electroencephalogram, respiration, blink and pain were recorded in minutes as well as a neurologic examination at 1, 2, and 3 days and pathologic examination of the brain at 3 days, both by blinded observers. MAIN RESULTS: There were no significant differences in the four groups. CONCLUSIONS: Polyethylene glycol-bound superoxide dismutase and catalase, and nimodipine, either alone or in combination, do not ameliorate hypoxic ischemic injury to the brain in the newborn pig when given 5 mins after reoxygenation.

Animals

Glucose affects the severity of hypoxic-ischemic brain injury in newborn pigs.

BACKGROUND AND PURPOSE: The administration of glucose has been shown to worsen brain injury in adult animals but has no effect on the severity of injury in newborn rats. We wished to see whether the results in newborn rats could be extended to another newborn animal. METHODS: In 44 0- to 3-day-old piglets, hypoxic-ischemic central nervous system damage was induced by ligation of both carotid arteries and reduction of their blood pressure to two-thirds normal for one-half hour. In the last 15 minutes of this half hour, oxygen concentration was reduced to 6%. The piglets were randomized to receive either 2 mL/kg 50% dextrose in water followed by 2 mL/kg per hour for 2.5 hours beginning before ischemia or enough insulin to reduce their resting blood sugar to approximately 2 mmol/L. RESULTS: Neurological exam scores in the glucose-treated piglets at 1 day after injury were significantly worse than those in the insulin-treated group. Pathological examination scores were poorer in the glucose-treated group (13.6 +/- 1.9 [mean +/- SEM]) than in the insulin-treated group (24.7 +/- 1.4, P < .01). CONCLUSIONS: Increasing serum glucose during hypoxic-ischemic injury to the newborn piglet's brain worsens brain injury.

Animals

Clinical and hemodynamic evaluation of the 19-mm Carpentier-Edwards supraannular aortic valve.

The clinical and hemodynamic performance of the 19-mm Carpentier-Edwards supraannular aortic valve is largely unknown compared with that of the larger valves. Over 4 years we implanted the 19-mm Carpentier-Edwards supraannular aortic valve into 21 patients (20 female) with a mean age of 75 +/- 1.2 years (range, 59 to 86 years) and a mean body surface area of 1.6 +/- 0.03 m2 (range, 1.3 to 1.7 m2). There were four deaths, one operative and three late noncardiac deaths. Follow-up of the 17 survivors for a mean of 20 +/- 3.1 months (range, 2 to 42 months) demonstrated symptomatic improvement in all 17 (all are now in New York Heart Association functional class I or II). There were no valve-related complications and no patient required long-term anticoagulation. Doppler echocardiographic studies were used to assess the in vivo hemodynamic profile of the valve. Mean postoperative aortic valve gradient was 34.1 +/- 2.7 mm Hg (range, 19 to 52 mm Hg). Functional valve orifice area was 1.1 +/- 0.09 cm2 (range, 0.6 to 1.8 cm2). Mean cardiac output was 3.92 +/- 0.17 L/min (range, 3.2 to 5.1 L/min) with a mean cardiac index of 2.5 +/- 0.11 L.min-1 x m-2 (range, 2.1 to 3.2 L.min-1 x m-2). In conclusion, we have demonstrated that aortic valve replacement with the 19-mm Carpentier-Edwards supraannular aortic valve has a low operative mortality and offers major clinical benefits despite moderate transprosthetic gradients. This approach provides an alternative management strategy in elderly patients who would otherwise require low-profile mechanical valves or aortic root enlargement.

Aged