Showing papers by "Sunnybrook Health Sciences Centre published in 1994"

A prospective study of venous thromboembolism after major trauma.

Abstract: Background Although deep-vein thrombosis and pulmonary embolism are considered common complications after major trauma, their frequency and the associated risk factors have not been carefully quantified. Methods We performed serial impedance plethysmography and lower-extremity contrast venography to detect deep-vein thrombosis in a cohort of 716 patients admitted to a regional trauma unit. Prophylaxis against thromboembolism was not used. Results Deep-vein thrombosis in the lower extremities was found in 201 of the 349 patients (58 percent) with adequate venographic studies, and proximal-vein thrombosis was found in 63 (18 percent). Three patients died of massive pulmonary embolism before venography could be performed. Before venography, only three of the patients with deep-vein thrombosis had clinical features suggestive of the condition. Deep-vein thrombosis was found in 65 of the 129 patients with major injuries involving the face, chest, or abdomen (50 percent); in 49 of the 91 patients with major hea...

Versatile retroviral vectors for potential use in gene therapy.

Abstract: A set of retroviral vectors is described whose capacity for high efficiency transduction of functional genes into undifferentiated murine embryonic and haematopoietic cells makes them ideally suited for preclinical studies with murine models. Multiple unique cloning sites permit insertion of genes into the vectors such that no selectable marker exists or either the neomycin phosphotransferase (neo) gene, the hygromycin B phosphotransferase (hph) gene or the puromycin N-acetyl transferase (pac) gene is included as a dominantly acting selectable marker. Because the sequences in the viral gag region shown to improve the encapsidation of viral RNA have been modified to prevent viral protein synthesis and all env sequences have been removed to eliminate helper virus production by homologous recombination with packaging DNA, these vectors might prove useful in human gene therapy protocols.

The quantitative analysis of mammographic densities

Abstract: Quantitative classification of mammographic parenchyma based on radiological assessment has been shown to provide one of the strongest estimates of the risk of developing breast cancer. Existing classification schemes, however, are limited by coarse category scales. In addition, subjectivity can lead to sizeable interobserver and intraobserver variations. Here, the authors propose an interactive thresholding technique applied to digitized film-screen mammograms, which assesses the proportion of the mammographic image representing radiographically dense tissue. Observers viewed images on a CRT display and selected grey-level thresholds from which the breast and regions of dense tissue in the breast were identified. The proportion of radiographic density was then calculated from the image histogram. The technique was evaluated for the mammograms of 30 women and is well correlated (R>0.91, Spearman coefficient) with a six-category subjective classification of radiographic density by radiologists. The technique was found to be very reliable with an intraclass correlation coefficient between observers typically R>0.9. This technique may have a role in routine mammographic analysis for the purpose of assessing risk categories and as a tool in studies of the etiology of breast cancer, in particular for monitoring changes in breast parenchyma during potential preventive interventions.

The airway: problems and predictions in 18,500 patients

Abstract: The purpose of this study was to describe methods, risk factors, and outcomes of airway management in all patients (obstetrics excluded) attended by anaesthetists over 27 months. Preoperatively, anaesthetists recorded patient factors and assessed four airway characteristics. Methods of tracheal intubation and ease of direct laryngoscopy following general anaesthesia (easy, awkward, difficult) were noted. Factors predictive of poor outcome and the value of the preoperative airway examination were determined. For 18,205 patients following a direct laryngoscopy, (GA), tracheal intubation was difficult (> 2 laryngoscopies) in 1.8% and awkward ( 200 mm Hg) and dental damage on induction of anaesthesia. It is concluded that difficult tracheal intubations occurred infrequently but were associated with increased morbidity. Patient factors and four physical airway characteristics were useful predictors but limited in identifying all problems.

The postoperative interview: assessing risk factors for nausea and vomiting.

Abstract: Most studies of postoperative nausea and vomiting have concentrated on single etiologic factors and have not detailed the method of assessing these symptoms. This study used postoperative interview data from patients at four teaching hospitals during 1988-89, to determine 1) risk factors for nausea/vomiting, 2) whether the type of surgery affected the rate of nausea/vomiting among female patients, 3) whether differences in rates across hospitals were due to differences in patient case-mix, and 4) whether there were differences in the rate of nausea/vomiting among the patients of individual anesthesiologists. Research nurses performed 16,000 interviews (59% of all inpatients) from a closed-question standardized format. With a multiple logistic regression that controlled simultaneously for all risk factors, factors associated with increased risk for nausea/vomiting for all patients included younger age, female, lower physical status score, no preoperative medical conditions, nonsmokers, elective procedures, longer duration of anesthesia, inhaled anesthetics, use of intraoperative opioids, and gynecologic or ophthalmologic operations. Among women, risk factors were similar, with minor gynecologic surgery associated with increased risk (relative odds = 2.30). We found marked variations in the rate of nausea/vomiting across hospitals (range, 39% to 73%), and these variations were not explained by the case-mix of patients. The rate of nausea/vomiting varied substantially across anesthesiologists in each hospital and the differences were not explained by differences in the patients they managed. Thus in the time period immediately preceding the introduction of newer antiemetic drugs, we found that the rates of this common problem were persistently high as perceived from the patients' point of view.

Anisotropy of NMR properties of tissues.

Abstract: Orientational anisotropy of T2 and T1 relaxation times, diffusion, and magnetization transfer has been investigated for six different tissues: tendon, cartilage, kidney, muscle, white matter, and optic nerve. Relaxation anisotropy was observed for tendon and cartilage, and diffusional anisotropy was measured in kidney, muscle, white matter, and optic nerve. All other NMR measurements of these tissues showed no orientational dependence. This pattern of NMR anisotropies can be interpreted from the underlying geometrical structures of the tissues.

Inhibition of nuclear hormone receptor activity by calreticulin

Abstract: We have shown that a polypeptide of M(r) 60,000 (60K) that shares N-terminal homology with a calcium-binding protein, calreticulin, can bind to an amino-acid sequence motif, KXGFFKR, found in the cytoplasmic domains of all integrin alpha-subunits. The homologous amino-acid sequence, KXFFKR (where X is either G, A or V), is also present in the DNA-binding domain of all known members of the steroid hormone receptor family; amino acids in this sequence make direct contact with nucleotides in their DNA-responsive elements and are crucial for DNA binding. Here we show that both the 60K protein (p60), purified on a KLGFFKR-Sepharose affinity matrix, and recombinant calreticulin can inhibit the binding of androgen receptor to its hormone-responsive DNA element in a KXFFKR-sequence-specific manner. Calreticulin can also inhibit androgen receptor and retinoic acid receptor transcriptional activities in vivo, as well as retinoic acid-induced neuronal differentiation. Our results indicate that calreticulin can act as an important modulator of the regulation of gene transcription by nuclear hormone receptors.

Induction of cyclin D1 overexpression by activated ras.

Abstract: Activated ras genes are known to alter control of cell proliferation. This is consistent with the fact that ras proteins are a key component of the biochemical pathway triggered by ligand-bound cell surface receptors that are tyrosine kinases. Although an important part of the ras signaling pathway has been recently uncovered, the molecular target(s) that mediates the effects of ras on cell cycle control remains unknown. Cyclins and cyclin-dependent kinases are key molecules in the control of cell cycle. Cyclin D1, in particular, is a critical target for proliferative signals in G1 and it has been shown that ectopic overexpression of this cyclin can significantly alter cell cycle regulation. Here we report that activated ras induces significant overexpression of cyclin D1 in epithelial cells derived from normal rat intestine and mouse mammary gland. A definitive causal role for activated ras in this overexpression is demonstrated by using intestinal cells transfected with an inducible ras expression vector. Treatment of the ras-transformed intestinal clones with anti-sense cyclin D1 oligonucleotides reduces their rate of cell proliferation indicating that the increment in cyclin D1 expression induced by activated ras is instrumental in the higher rate of cell proliferation conferred by the ras oncogene to the IEC cells. Based on these results we propose that, at least in certain cell types, cyclin D1 can be one of the mediators of the transforming action of activated ras.

Antifungal agents: An overview. Part II

Abstract: The last decade has witnessed remarkable advances in the therapy for cutaneous fungal diseases. These will have a major impact on the choice of antifungal therapy. To understand these advances traditional therapies for fungal diseases, the polyenes, griseofulvin, older topical agents and the older azoles, will be reviewed first. Part II will focus on recent advances.

Critical respiratory events in the postanesthesia care unit. Patient, surgical, and anesthetic factors.

Abstract: BACKGROUND Previous studies have noted a high incidence of adverse outcomes in the postanesthesia care unit (PACU), but few have examined associated factors and patient outcomes. To determine the frequency of acute, unanticipated respiratory problems and to examine the associated patient, surgical, and anesthetic factors, we prospectively collected preoperative, intraoperative, and postoperative data on 24,157 consecutive PACU patients who received a general anesthetic during a 33-month period. METHODS A PACU critical respiratory event (CRE), was defined as any unanticipated hypoxemia (hemoglobin oxygen saturation 50 mmHg) or upper-airway obstruction (stridor or laryngospasm) requiring an active and specific intervention (ventilation, tracheal intubation, opioid or muscle relaxant antagonism, insertion of oral/nasal airway or airway manipulation). These problems were documented by PACU nurses whereas data on case-mix, surgical factors, and intraoperative management were retrieved from the anesthetic record. Significant patient, surgical, and anesthetic factors were identified by logistic regression analysis. Other morbidity experienced by patients with a CRE was also noted. RESULTS For patients given general anesthesia the risk of a CRE was 1.3% (hypoxemia 0.9%, hypoventilation 0.2%, airway obstruction 0.2%). Preoperative factors that increase risk were age > 60 yr, male gender, diabetes, and obesity (P 2.0 micrograms.kg-1.h-1 as the sole opioid (1.9), fentanyl used in combination with morphine (1.6) and atracurium > or = 0.25 mg.kg-1.h-1 (2.2). Patients in whom anesthesia was induced with thiopental (relative odds 2.5), compared with those who received propofol for induction, were also at increased risk of a CRE. Patients with a CRE stayed longer in PACU, had higher rates of unanticipated admissions to the intensive care unit and were more likely to have PACU cardiac problems (P < 0.01). CONCLUSIONS A CRE is relatively rare. Multiple patient and surgical factors and specific aspects of anesthetic management are associated with the occurrence of a CRE in the PACU.

Extent of vascularization as a prognostic indicator in thin (< 0.76 mm) malignant melanomas.

Abstract: Angiogenesis in malignant melanoma (MM) was evaluated by comparing mean vessel number (MVN) in Spitz's nevi (SN), thick and thin MMs that metastasized, and thick and thin MMs with > or = 10-year survival. Vessels were identified with antibodies against factor VIII-related antigen (FVIII) and CD34 in 37 MMs (17 or = 4.0 mm) with > or = 10-year follow-up and 10 SN from children ( or = 5.5 mm) and five pairs ( or = 5.5 mm, there was no correlation with MVN with either metastasis or death (FVIII P = 0.98; CD34 P = 0.85). Among the thin paired lesions, high MVN (FVIII = 46, CD34 = 39) was significantly related not only to metastasis (FVIII P = 0.04, CD34 P = 0.03) but also to death (FVIII P = 0.04, CD34 P = 0.05). MVN does not separate SN versus MM nor predict outcome in thick (> or = 4.0 mm) MMs; however, high MVN (> or = 42 average) is predictive of metastasis and death in MMs < or = 0.75 mm. Larger matched studies are indicated to confirm this observation.

Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons.

Abstract: Propofol (2,6 di-isopropylphenol) is an alkyphenol recently introduced for use as a general anesthetic. The modulation of GABAA receptor activation and desensitization by propofol was studied using a rapid perfusion system and whole-cell voltage-clamp recordings from mouse hippocampal neurons. The effects of concentrations of propofol used clinically on single-channel and synaptic currents were also examined. Propofol evoked current responses (EC50 = 61 microM) and shifted the dose-response curve of GABA-activated current to the left without altering the maximum of the GABA response. Preincubation with propofol and GABA led to desensitization of the GABA response (EC50 = 454 microM and 23 microM, respectively). Saturating concentrations of GABA (600 microM) evoked currents that peaked and then declined in a biexponential fashion with fast and slow time constants of tau f = 1.0 sec and tau s = 3.5 sec. Propofol (10 microM) did not change the amplitude of the peak response but decreased the rates of decay approximately 1.5-fold and enhanced the steady-state current proportionately. Recovery from desensitization was also biexponential (tau f = 11 sec, tau s = 69 sec) but not influenced by propofol. Single-channel recordings from outside-out patches demonstrated that both propofol and GABA activated channels with a 30 pS and 21 pS open state. Propofol increased the frequency but not the duration or conductance of GABA-activated events. Miniature inhibitory postsynaptic currents (mlPSCs) were evoked by the application of hypertonic sucrose to the cell soma. Propofol (2 microM) prolonged the decay time of mlPSCs to an extent similar to which it increased the open probability of GABA-activated channels (2.3- vs 3-fold). A sequential model, based on a previous scheme of GABA receptor gating (Weiss and Magelby, 1989), is presented to summarize propofol's actions on GABAA receptor function. We show through simulation that the model reliably reproduced the whole-cell tracings. Our results indicate that propofol's neurodepressive actions will be associated with enhancement of inhibitory synaptic transmission.

Prevalence of serum antibodies against the p53 tumor suppressor gene protein in various cancers.

Abstract: We have developed 2 new quantitative methods for measuring anti-p53 antibodies in human serum. Using these methods we analyzed 1,392 sera from patients with various malignancies and 230 sera from individuals without malignancy. Highest prevalence of anti-p53 antibodies was associated with ovarian and colon cancers (15%), followed by lung (8%) and breast (5%) cancers. Prevalence in other malignancies was lower ( 10(5) U/L) were found in 5 ovarian, 2 breast, 1 lung and 1 colon cancers. Sequential analysis of 6 positive samples has shown that the p53 antibody test may have potential for patient monitoring. The p53 antibody-positive sera from breast cancer patients were associated with tumors that were steroid hormone receptor-negative (p < 0.002). We propose that the measurement of p53 antibodies is a relatively specific serological test for cancer, which can be performed with easily automatable and quantitative methodologies and may be further exploited for patient monitoring, prognosis, diagnosis and probably screening for selected cancers.

The laryngeal mask airway and positive-pressure ventilation.

Abstract: BACKGROUND The utility of the laryngeal mask airway during positive-pressure ventilation has yet to be determined. Our study was designed to assess whether significant leaks occurred with positive-pressure ventilation and if leaks were associated with gastroesophageal insufflation. METHODS Forty-eight patients undergoing elective surgery were studied. After induction of anesthesia and paralysis, controlled ventilation was used with four different peak pressure settings in each patient (15, 20, 25, and 30 cmH2O). The order of ventilator pressure settings was assigned from a randomized block schedule. Data collected included inspiratory and expiratory volumes, qualitative assessments of gastroesophageal insufflation, and leak at the neck. After data collection during laryngeal mask use, the anesthesiologist intubated the trachea and measurements were repeated for tracheal tube ventilation. Leak was calculated by subtracting the expiratory from the inspiratory volume and expressed as a fraction of the inspiratory volume. RESULTS Ventilation with the laryngeal mask airway was adequate at all ventilation pressures and comparable with tracheal tube ventilation. Leak fraction (mean +/- SD) at 15, 20, 25, and 30 cmH2O for laryngeal mask ventilation were 0.13 +/- 0.15, 0.21 +/- 0.18, 0.25 +/- 0.16 and 0.27 +/- 0.17, respectively, and 0.03 +/- 0.03, 0.05 +/- 0.03, 0.05 +/- 0.03 and 0.04 +/- 0.03, respectively, for tracheal tube ventilation. Leak fractions for ventilation with the laryngeal mask were consistently greater than those measured for tracheal tube ventilation at similar ventilation pressures. Leak fraction with laryngeal mask ventilation increased with increasing airway pressures, whereas leak with tracheal tube ventilation remained unchanged. The frequency of gastroesophageal insufflation ranged from 2.1% at a ventilation pressure of 15 cmH2O to 35.4% at 30 cmH2O. CONCLUSIONS Ventilation using the laryngeal mask appears to be adequate if airway resistance and pulmonary compliance are normal. Gastroesophageal insufflation of air will become a problem in the presence increased ventilation pressure.

The laryngeal mask airway and positive-pressure ventilation

Abstract: Background: The utility of the laryngeal mask airway during positive-pressure ventilation has yet to be determined. Our study was designed to assess whether significant leaks occurred with positive-pressure ventilation and if leaks were associated with gastroesophageal insufflation. Methods: Forty-eight patients undergoing elective surgery were studied. After induction of anesthesia and paralysis, controlled ventilation was used with four different peak pressure settings in each patient (15, 20, 25, and 30 cmH 2 O). The order of ventilator pressure settings was assigned from a randomized block schedule. Data collected included inspiratory and expiratory volumes, qualitative assessments of gastroesophageal insufflation, and leak at the neck. After data collection during laryngeal mask use, the anesthesiologist intubated the trachea and measurements were repeated for tracheal tube ventilation. Leak was calculated by subtracting the expiratory from the inspiratory volume and expressed as a fraction of the inspiratory volume. Results: Ventilation with the laryngeal mask airway was adequate at all ventilation pressures and comparable with tracheal tube ventilation. Leak fraction (mean±SD) at 15, 20, 25, and 30 cmH 2 O for laryngeal mask ventilation were 0.13±0.15, 0.21±0.18, 0.25±0.16 and 0.27±0.17, respectively, and 0.03±0.03, 0.05±0.03, 0.05±0.03 and 0.04±0.03, respectively, for tracheal tube ventilation. Leak fractions for ventilation with the laryngeal mask were consistently greater than those measured for tracheal tube ventilation at similar ventilation pressures. Leak fraction with laryngeal mask ventilation increased with increasing airway pressures, whereas leak with tracheal tube ventilation remained unchanged. The frequency of gastroesophageal insufflation ranged from 2.1% at a ventilation pressure of 15 cmH 2 O to 35.4% at 30 cmH 2 O. Conclusions: Ventilation using the laryngeal mask appears to be adequate if aiway resistance and pulmonary compliance are normal. Gastroesophageal insufflation of air will become a problem in the presence increased ventilation pressure

Cell attachment to extracellular matrix substrates is inhibited upon downregulation of expression of calreticulin, an intracellular integrin alpha-subunit-binding protein

Abstract: We have demonstrated recently that calreticulin, an intracellular calcium-binding protein, can interact with the alpha-subunits of integrin receptors via the highly conserved KXGFFKR amino acid sequence present in the cytoplasmic domains of all integrin alpha-subunits (Rojiani et al. (1991) Biochemistry 30, 9859-9866). Here we demonstrate that calreticulin can be co-localized by immunofluorescence as well as co-purified with integrins, that recombinant calreticulin can also interact with integrins, and that the interaction occurs predominantly via the N-domain of calreticulin, to a much lesser extent with the C-domain, but not at all with the proline-rich P-domain. To demonstrate a physiological role for the interaction of calreticulin with integrins, calreticulin expression was downregulated by treating cells with antisense oligonucleotides designed to inhibit the initiation of translation of calreticulin. Antisense oligonucleotides, but not sense or non-sense oligonucleotides, inhibited attachment and spreading of cells cultured in the presence of fetal bovine serum, and also of cells plated on individual extracellular matrix substrates in the absence of serum. The antisense oligonucleotide inhibited cell proliferation of anchorage-dependent cells slightly, but there was no effect on cell viability. The effect on cell attachment was similar to that achieved by treating cells with an antisense oligonucleotide designed to inhibit translation of the integrin alpha 3 subunit, which resulted in the inhibition of cell attachment to alpha 3 beta 1-specific substrates. The effect of the antisense calreticulin oligonucleotide on cell attachment was demonstrated to be integrin-mediated since antisense calreticulin treatment of Jurkat cells abrogated the stimulation of collagen cell attachment achieved by attachment-stimulating signalling anti-alpha 2 (JBS2) and anti-beta 1 (21C8) antibodies. The oligonucleotides did not affect the rate of cell proliferation of these cells. These results demonstrate a fundamental role of calreticulin in cell-extracellular matrix interactions.

Spinal cord tumors in children: long-term results of combined surgical and radiation treatment.

Abstract: ✓ The authors report a series of 31 children under 17 years of age with primary spinal cord tumors who underwent radiation treatment following decompression laminectomy with or without tumor resection between 1959 and 1990. The tumors consisted of 15 astrocytomas, 11 ependymomas, one mixed glioma, one ganglioglioma, and three of unknown histology. Ten- and 20-year survival rates and 10- and 20-year relapse-free survival rates for the 28 patients with known histology were 80% and 53%, and 73% and 67%, respectively. Eleven patients (35%) had no resection, 14 (45%) had a partial resection, and six (19%) had a grossly complete resection. Eight patients (26%) are dead: five due to recurrent tumor, two due to a second malignant tumor, and one due to intercurrent disease. Primary tumor relapse or progression occurred in nine patients (29%), four of whom were salvaged. A second malignant tumor developed in four patients (13%), two of whom died. Local control of the tumor was finally achieved in 26 cases (84%), de...

Fabrication of high frequency spherically shaped ceramic transducers

Abstract: Difficulty in obtaining well focused efficient ultrasound transducers has limited the development of new high frequency applications of B-mode imaging. This paper describes a method for fabricating high frequency (53 MHz) spherically focused lead zirconate titanate (PZT) transducers. A transducer is fabricated by bonding a malleable backing layer onto a thin plate of PZT and then pressing the plate into a spherically shaped well. The backing layer evenly distributes stresses across the material when it is pressed into the well. Local concentrations of stress which lead to fracture are avoided and the material can be deformed without macroscopic cracking. The characteristics of a 2 mm diameter 53 MHz PZT transducer with a 4 mm focal length are described. A lateral beam width of 68 /spl mu/m and a 12 dB depth of field of 1.5 mm were obtained. The minimum two-way insertion loss of the system was /spl minus/25 dB and the 6 dB bandwidth of the pulse echo response was 30%. An image of a resolution phantom and an in vivo skin image illustrate the excellent imaging characteristics of the transducer. >

Retroviral integration within the Fli-2 locus results in inactivation of the erythroid transcription factor NF-E2 in Friend erythroleukemias: evidence that NF-E2 is essential for globin expression.

Abstract: Activation of either Fli-1 or Spi-1 members of the ets family of transcription factors as a result of retroviral insertion and mutational inactivation of the p53 tumor suppressor gene play essential roles in the multistage erythroleukemias induced in mice by various strains of Friend virus. We have previously identified another common site for provirus integration, designated Fli-2 (Friend leukemia integration 2), in some erythroleukemia clones induced either by Friend murine leukemia virus (F-MuLV) or by the polycythemia-inducing strain of Friend virus complex (FV-P). Here we show that genomic sequences adjacent to Fli-2 correspond to the coding region of the erythroid-specific DNA binding protein NF-E2 p45. In one erythroleukemia cell line the expression of NF-E2 p45 is undetectable due to proviral integration in one allele and loss of the other allele. The complete loss of NF-E2 p45 in this cell line is associated with a drastic reduction in expression of the alpha- and beta-globin genes that were partially restored by reintroduction of the NF-E2 p45 gene. Taken together, these results provide direct evidence that NF-E2 gene is essential for globin transcription and suggest that perturbation in expression of this transcription factor may contribute to erythroleukemia progression.

Cardiopulmonary bypass, temperature, and central nervous system dysfunction.

Abstract: BACKGROUND Neurological injury is an important cause of morbidity and mortality after cardiac surgery. With the advent of warm heart surgery, the neuroprotective role of hypothermic cardiopulmonary bypass (CPB) has come under increasing scrutiny. Preliminary work by us in the area found no increased risk of neurological morbidity with normothermic CPB in a small group of patients and suggested a possible benefit. The purpose of the present study is to compare the incidence of neurological and neuropsychological dysfunction in a larger number of patients randomized to warm or cold aortocoronary bypass surgery. METHODS AND RESULTS With the approval of the institutional research ethics committee, 201 aortocoronary bypass patients were randomized to normothermic or moderate hypothermic CPB and subjected to neurological and neuropsychological evaluation. These subjects were a subset of patients enrolled in a large multicenter trial comparing warm versus cold heart surgery. The examinations took place preoperatively, 5 days after operation, and a 3-month follow-up. The examination consisted of a clinical neurological examination and a brief neuropsychological test battery. The neuropsychological tests included the Buschke selective reminding procedure, the Wechsler memory scale-revised visual reproduction subtest, the trial making test (parts A and B), the Wechsler adult intelligence scale-revised digit symbol subtest, and the grooved pegboard test. The examiner and subjects were unaware of the CPB temperature allocation (warm, > 34 degrees C; cold, < or = 28 degrees C). Statistical analysis was performed using the SAS statistical software package. Two hundred one patients were enrolled in the study. Of these, 155 patients completed the entire protocol and were included in the final analysis (warm group, n = 78; cold group, n = 77). One patient in the warm group died perioperatively from a massive hemispheric stroke. Another warm group patient was unable to complete neuropsychological evaluation because of a perioperative stroke. Thus, 153 patients completed the entire series of neuropsychological tests. A total of 6 patients (warm group, n = 2; cold group, n = 4; P = NS) suffered from perioperative focal neurological deficits. There was a consistent deterioration in scores from tests of psychomotor speed/coordination (trial making, digit symbol, pegboard) in the early postoperative period, which resolved by the 3-month follow-up. Tests of memory (Buschke, Wechsler memory scale) showed no evidence of patient deterioration in the postoperative period. No difference was seen between the warm and cold groups. CONCLUSIONS In this randomized trial of normothermic versus hypothermic CPB, we found deterioration in scores of tests of psychomotor speed but not of memory in the early postoperative period. We were unable to demonstrate any neuroprotective effect from moderate hypothermia in this patient population.

A prospective study of emergent abdominal sonography after blunt trauma.

Abstract: In North America, the role of emergent abdominal sonography [ultrasonography (US)] after blunt trauma requires further definition. The purpose of this prospective study was to compare US to the gold standards, diagnostic peritoneal lavage (DPL), and computed tomography (CT), in a population of adults after blunt trauma. In 206 adults who required either CT or DPL to assess possible abdominal injury, US was performed, before DPL or CT, and was aimed at the detection of intraperitoneal fluid. The mean Injury Severity Score and Glasgow Coma Scale score were 24.0 and 11.9, respectively. One hundred thirty-seven patients (67%) had CT and 69 (33%) had DPL. The positive and negative predictive values of US for intraperitoneal fluid were 90% and 97%, respectively. The sensitivity, specificity, and accuracy of US for free fluid were 81%, 98%, and 96%, respectively. Of the six false-negative USs, only one required surgery. The US examinations required 2.6 +/- 1.4 min. Emergent abdominal sonography is an accurate, rapid test for the presence of intraperitoneal fluid in adult blunt trauma victims and in these patients may prove valuable as a screening test for abdominal injury.

Response to Desipramine Treatment in Adolescent Depression: A Fixed-Dose, Placebo-Controlled Trial

Abstract: Objective To determine the efficacy and tolerability of the tricyclic antidepressant desipramine (DMI) in the treatment of DSM-III-R-diagnosed major depressive disorder in adolescents. Method Sixty adolescents (42 female, 18 male; aged 15 to 19 years) diagnosed with major depressive disorder using clinical interview and Schedule for Affective Disorders and Schizophrenia for School-Age Children were randomized to receive either DMI (200 mg daily in divided doses) or placebo for six consecutive weeks following a 1-week placebo period. Treatment outcome was determined using the Hamilton Depression Rating Scale and the Beck Depression Inventory. Tolerability was determined using a symptom side effects scale. In addition, a variety of laboratory and cardiovascular monitoring was performed. Results No significant differences in treatment outcome between DMI- and placebo-treated groups were determined. Neither DMI, nor its metabolite 2-hydroxy-DMI, nor their ratio, was positively correlated to treatment outcome. The DMI group endorsed more side effects but there were no significant between-group differences in any laboratory, electrocardiographic, or other cardiovascular parameters apart from heart rate, which was increased in the DMI-treated group ( p = .03). Conclusions Given the findings of this study and our review of previously published reports of tricyclic antidepressant treatment in this population, the routine use of short-term (6 weeks) DMI in the treatment of adolescent depression is not supported by the data on hand. Further investigations into what constitutes optimal psychopharmacological treatment of adolescent depression are warranted.

Cost of acute stroke care in Toronto, Canada.

Abstract: Stroke cost consumes a large proportion of the gross domestic product in all developed countries, and while health care costs are rising, the ability to contain them is diminishing. We calculated the cost of acute stroke care for all first admissions to a teaching hospital in Toronto, Canada, in 1991 through 1992 for 285 consecutive patients. The average cost per patient was $27,500 Canadian, and strokes in men cost less than in women ($23,000 versus $32,000 Canadian), for a total cost of $8 million Canadian over 2 years. More women died than men (34% versus 17%, P < .02), mainly from systemic complications of stroke, but because women stayed hospitalized longer, they cost more in the long term. The major factor determining cost was social support, and more men than women went home or to rehabilitation units (P < .02). Family support was greater for men (82%) than women (39%, P < .0002). Significant cost reductions are more likely to be achieved by altering discharge policies and improving social conditions for early return to the home than by reducing laboratory or medical personnel costs.

Intrinsic or acquired drug resistance and metastasis: Are they linked phenotypes?

Abstract: Evidence is reviewed which suggests a linkage may exist between certain forms of de novo or acquired drug resistance and metastasis. This includes the finding that expression of certain dominantly acting mutant oncogenes or tumor suppressor genes, i.e., genes which normally act to "drive" tumor progression and metastasis, can also affect the expression of drug resistance. Moreover, this can be accompanied by altered expression of certain cellular genes thought to be involved in expression of drug resistance. A direct linkage between acquired drug resistance and metastasis would suggest that tumor sublines selected for drug resistance should manifest more aggressive malignant properties than their drug-sensitive counterparts. While this does not appear to be true for drug resistant sublines selected in vitro, indeed such cell lines frequently manifest diminished in vivo tumorigenic and/or metastatic competence, there is some evidence to support such a correlation exists for tumor cell lines that are selected in vivo for drug resistance. Attention is also drawn to the fact that new linkages between metastasis and drug resistance may be uncovered by analyzing the ability of tumor subpopulations to acquire drug resistance after one or several previous exposures to chemotherapeutic drugs, as opposed to examining intrinsic drug resistance only. Furthermore, ability to detect induced or acquired drug resistance in vitro may be strongly influenced by the types of assay used to detect and monitor drug resistance. In particular, three-dimensional cell culture systems may reveal acquired or induced "multicellular" drug resistance in situations where conventional two-dimensional culture systems do not. Use of three-dimensional culture systems may therefore reveal as yet undiscovered associations between the phenotypes of metastasis and drug resistance.

An anaesthetic drug error: minimizing the risk.

Abstract: A medication error caused a near fatal cardiac arrest in a previously healthy patient undergoing elective surgery. Inadvertent epinephrine injection induced ventricular dysrhythmias, hypertension, hypotension and pulmonary oedema. The case was investigated using critical-incident technique and was reviewed by the Risk Management Team of the Department of Anaesthesia. The purpose of this report is to present the recommendations resulting from the investigation. These include: improved resident training in intravenous drug management, the use of anaesthetic drug ampoules with distinct labels, and the development of a standardized colour code system for labels on anaesthetic drug ampoules. Furthermore, it is recommended that all anaesthetic drug errors be reported to the Canadian agencies responsible for drug packaging in order to identify patterns in anaesthetic drug errors, and to facilitate the implementation of effective drug identification systems.

The HOX11 homeobox-containing gene of human leukemia immortalizes murine hematopoietic precursors.

Abstract: The t(10;14) chromosomal translocation of T-cell acute lymphoblastic leukemia joins the T-cell receptor delta gene to a region upstream of a diverged homeobox-containing gene called HOX11. To better understand the pathogenetic role of HOX11 in leukemogenesis, post 5-fluorouracil-treated murine bone marrow cells were infected with a replication-defective retrovirus bearing the gene. Constitutive expression of HOX11 in hematopoietic precursors yielded cell lines at high frequency consisting of immature cells belonging to the myeloid lineage. HOX11-transformed cell lines displayed a strict dependence on IL-3 for their survival and proliferation in culture and were not leukemogenic. The results support the hypothesis that the transforming capacity of HOX11 derives from its ability to alter the expression of genes regulating hematopoietic differentiation and that secondary mutations promoting cell survival or stimulating proliferation are required for progression to malignancy. The findings further suggest that the oncogenic activity of HOX11 might not be restricted to T-cell leukemias in humans.

Intracranial blood flow velocities in acute ischemic stroke.

Abstract: Transcranial Doppler sonography (TCD) can evaluate noninvasively the blood flow velocities and patency of the main trunk of the middle cerebral artery (MCA). Using TCD we evaluated MCA patency and patterns of flow through the circle of Willis in patients with acute stroke.Patients with symptoms of hemispheric stroke were evaluated with serial TCD tests during admission. The Canadian Neurological Scale was used to assess neurological deficits. In all cases computed tomographic scan, 99mTc hexamethylpropyleneamine oxime single-photon emission computed tomography, and carotid duplex were performed, and in some cases cerebral angiography.Seventy-five consecutive patients with symptoms of acute ischemic stroke (mean time, 8 +/- 4 hours) were studied. Four circle of Willis perfusion patterns were observed: normal, collateral, stenotic, and occlusive. MCA occlusion or stenosis was seen in 70% of initial TCD studies in the stroke group (n = 50) but not in patients with transient ischemic attacks (n = 25). Eighty-...

Optimization of spectral shape in digital mammography: Dependence on anode material, breast thickness, and lesion type

Abstract: It has been proposed that breast cancerdetection can be improved through the use of digital mammography. It is hypothesized that the choice of proper shape of the x‐ray spectrum incident upon the breast can yield an improved image signal‐to‐noise ratio (SNR) for a given dose. To test this hypothesis, an energy transport model incorporating measured breast tissue attenuation coefficients and published exposure‐to‐dose conversion values was developed to describe the image acquisition process. The choice of applied kilovoltage and filter for Mo and W target x‐ray sources has been optimized with respect to SNR and absorbed dose for detectors based on a Gd2O2S scintillating screen under the conditions of perfect coupling of light between the screen and a solid state photodetector. For the W spectra, the optimum filter–kVp combinations could provide 41%, 13%, and 42% improvements in SNR for 2‐cm, 6‐cm and 8‐cm breasts, respectively, over the conventional Mo filtration, for a practical imaging time of 1.0 s. W and Mospectra produce similar SNR values for a given filter thickness except for the 4‐cm breast. Given the limitations of current technology, however, the W spectra produce the optimum SNRs in a shorter imaging time for breast thicknesses greater than and less than 4 cm. The maximum SNR for imaging both infiltrating ductal carcinoma and calcifications is provided by the same filter–kVp combination, allowing optimization based on breast thickness and composition only. The model can now be used to compare and improve upon novel detector designs.