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Credentials

Education ?

Medical School Score Rankings
The University of Texas Southwestern (1989)
  •  
Top 25%

Awards & Distinctions ?

Awards  
Young Investigator Award Finalist: Shock Society
Excellence in Resident Teaching Award, Department of Surgery, UTSW Medical Center at Dallas
Academic Excellence Award, Department of Surgery, UTSW Medical Center at Dallas
Snyder-Laycock Teaching Award, Department of Surgery, UTSW Medical Center at Dallas
Excellence in Resident Teaching Award, Department of Surgery, UTSW Medical Center at Dallas (2002)
Academic Excellence Award, Department of Surgery, UTSW Medical Center at Dallas (1994)
Snyder-Laycock Teaching Award, Department of Surgery, UTSW Medical Center at Dallas (2003)
Young Investigator Award Finalist: Shock Society (1995)
Associations
American Board of Surgery
American College of Surgeons

Affiliations ?

Dr. Murphy is affiliated with 8 hospitals.

Hospital Affiliations

Score

Rankings

  • UT Southwestern University Hospital - St. Paul
    5909 Harry Hines Blvd, Dallas, TX 75235
    •  
    Top 25%
  • UT Southwestern University Hospital - Zale Lipshy
    5151 Harry Hines Blvd, Dallas, TX 75235
    •  
    Top 25%
  • Children's Medical Center of Dallas
    Pediatric Surgery
    1935 Motor St, Dallas, TX 75235
    •  
    Top 50%
  • Parkland Health & Hospital System
    5201 Harry Hines Blvd, Dallas, TX 75235
    •  
  • Dallas County Hospital District
  • Abington Hospital
  • Dallas County Va Hospital Systems
  • UT Southwestern Zale Lipshy Hospital
  • Publications & Research

    Dr. Murphy has contributed to 155 publications.
    Title Is It Necessary to Drain All Postoperative Fluid Collections After Appendectomy for Perforated Appendicitis?
    Date October 2011
    Journal Journal of Pediatric Surgery
    Excerpt

    Children treated for perforated appendicitis can have significant morbidity. Management often includes looking for and draining postoperative fluid collections. We sought to determine if drainage hastens recovery.

    Title Histidine Protects Against Zinc and Nickel Toxicity in Caenorhabditis Elegans.
    Date July 2011
    Journal Plos Genetics
    Excerpt

    Zinc is an essential trace element involved in a wide range of biological processes and human diseases. Zinc excess is deleterious, and animals require mechanisms to protect against zinc toxicity. To identify genes that modulate zinc tolerance, we performed a forward genetic screen for Caenorhabditis elegans mutants that were resistant to zinc toxicity. Here we demonstrate that mutations of the C. elegans histidine ammonia lyase (haly-1) gene promote zinc tolerance. C. elegans haly-1 encodes a protein that is homologous to vertebrate HAL, an enzyme that converts histidine to urocanic acid. haly-1 mutant animals displayed elevated levels of histidine, indicating that C. elegans HALY-1 protein is an enzyme involved in histidine catabolism. These results suggest the model that elevated histidine chelates zinc and thereby reduces zinc toxicity. Supporting this hypothesis, we demonstrated that dietary histidine promotes zinc tolerance. Nickel is another metal that binds histidine with high affinity. We demonstrated that haly-1 mutant animals are resistant to nickel toxicity and dietary histidine promotes nickel tolerance in wild-type animals. These studies identify a novel role for haly-1 and histidine in zinc metabolism and may be relevant for other animals.

    Title Prehospital Cardiopulmonary Resuscitation in the Pediatric Trauma Patient.
    Date November 2010
    Journal Journal of Pediatric Surgery
    Excerpt

    Children requiring prehospital cardiopulmonary resuscitation (CPR) after traumatic injury have been shown to have poor survival. However, outcome of children still receiving CPR on-arrival by emergency medical service to the emergency department (ED) has not been demonstrated in a published clinical series.

    Title General and Family Practice-epitomes of Progress: Culdocentesis to Diagnose Ectopic Pregnancy and Pelvic Inflammatory Disease (pid).
    Date June 2010
    Journal The Western Journal of Medicine
    Title Transrectal Ultrasound and Fluoroscopy-guided Drainage of Deep Pelvic Collections in Children.
    Date June 2010
    Journal Journal of Pediatric Surgery
    Excerpt

    Pediatric deep pelvic abscesses generally occur as a complication of perforated appendicitis or after laparoscopic appendectomy. We describe our technique and experience in imaging-guided transrectal drainage (TRD) of deep pelvic abscesses in children.

    Title Responses to Active and Passive Wrist Rotation in Area 5 of Awake Monkeys.
    Date December 2009
    Journal Neuroscience Letters
    Title A Computational Model of Antibiotic-resistance Mechanisms in Methicillin-resistant Staphylococcus Aureus (mrsa).
    Date December 2008
    Journal Journal of Theoretical Biology
    Excerpt

    An agent-based model of bacteria-antibiotic interactions has been developed that incorporates the antibiotic-resistance mechanisms of Methicillin-Resistant Staphylococcus aureus (MRSA). The model, called the Micro-Gen Bacterial Simulator, uses information about the cell biology of bacteria to produce global information about population growth in different environmental conditions. It facilitates a detailed systems-level investigation of the dynamics involved in bacteria-antibiotic interactions and a means to relate this information to traditional high-level properties such as the Minimum Inhibitory Concentration (MIC) of an antibiotic. The two main resistance strategies against beta-lactam antibiotics employed by MRSA were incorporated into the model: beta-lactamase enzymes, which hydrolytically cleave antibiotic molecules, and penicillin-binding proteins (PBP2a) with reduced binding affinities for antibiotics. Initial tests with three common antibiotics (penicillin, ampicillin and cephalothin) indicate that the model can be used to generate quantitatively accurate predictions of MICs for antibiotics against different strains of MRSA from basic cellular and biochemical information. Furthermore, by varying key parameters in the model, the relative impact of different kinetic parameters associated with the two resistance mechanisms to beta-lactam antibiotics on cell survival in the presence of antibiotics was investigated.

    Title Patterns of Subgrouping and Spatial Affiliation in a Community of Mantled Howling Monkeys (alouatta Palliata).
    Date November 2008
    Journal American Journal of Primatology
    Excerpt

    Studies of social affiliation and social spacing offer important insight into the dynamics of subgroup formation and social strategies in living primates. Among the 11 species in the genus Alouatta, mantled howlers (A. palliata) are the only species to consistently form large, stable social groups composed of several adult males and several adult females. In this study, we examine patterns of subgrouping, activity, and partner preferences in a troop of 26-29 wild mantled howling monkeys (including 12-13 marked individuals) inhabiting Isla de Ometepe, Nicaragua. During two study seasons in 2000 and 2001, we simultaneously monitored the size, composition, and activities of individuals in two to three different subgroups. A half-weight association index was used to calculate partner preferences and patterns of spatial association. Results indicate that our howler study troop fragmented into subgroups of 1-20 with subgroups averaging five and six individuals. Subgroup size and membership reflected individual patterns of social affiliation and social tolerance, and in general remained consistent across activities and from year to year. We also found evidence of cliques or social networks of three to four individuals embedded within larger subgroups. A small number of adult males appeared to play an important social role as the nucleus of clique formation. We argue that the persistence of strong male-male and male-female partner preferences in mantled howlers helps to explain the stability of relatively large multimale-multifemale groups.

    Title Quinsy Trainer.
    Date March 2008
    Journal The Journal of Laryngology and Otology
    Excerpt

    The implementation of the European Working Time Directive, from the Council of the European Union (93/104/EC), in August 2004 has provoked a change in the working hours of junior doctors in the United Kingdom. With the evolution of the subsequent cross-cover arrangements combined with the modernising of medical careers,(1) training is becoming increasingly important. Here we present a simple method of teaching junior doctors the skills and competencies required to aspirate a peritonsillar abscess or 'quinsy'. The model is easy to construct, low cost and reusable.

    Title Use of a Pediatric Cohort to Examine Gender and Sex Hormone Influences on Outcome After Trauma.
    Date January 2008
    Journal The Journal of Trauma
    Excerpt

    BACKGROUND: Animal studies suggest that female gender imparts a protective effect on outcome after trauma, and implicate sex hormones as the cause. Human studies have yielded mixed results. These results are confounded by postmenopausal hormone replacement and the difficulty of controlling for pretrauma comorbidities. The pediatric population is a better model to determine the impact of gender and sex hormones on outcome after trauma. METHODS: The National Trauma Data Bank was queried for all patients from birth to 20 years of age. Age, gender, Injury Severity Score (ISS), mechanism of injury, mortality, intensive care unit days, and ventilator days were examined. To control for the effect of sex hormones, patients were divided into three groups by age: prepubertal (birth to 8 years), peripubertal (8.1-14.5 years), and postpubertal (14.6-20 years). We calculated survival rates for age group ISS subsets overall and by mechanism of injury.RESULTS: The prepubertal and peripubertal age groups had equivalent survival rates between genders across all severities of injury. The sex hormone-containing postpubertal cohort had a significantly improved survival rate for women across all ISS subgroups, and the effect was more pronounced with increasing ISS. This effect was despite a higher mean ISS for women at these greater magnitudes of injury. The cause of this effect could not be explained by mechanism of injury, ventilator days, or intensive care unit days. CONCLUSION: Female gender was associated with improved survival rates for patients demonstrating sex hormone production (i.e. postpubescent patients) in a manner that was directly proportional to their severity of injury. No protective effect of gender was seen in the prepubescent or peripubertal age groups.

    Title Balancing Perioperative Risks in Orthopedic Surgery: the Patient with a Coronary Stent.
    Date December 2007
    Journal Orthopedics
    Title Doe/netl's Phase Ii Mercury Control Technology Field Testing Program: Preliminary Economic Analysis of Activated Carbon Injection.
    Date August 2007
    Journal Environmental Science & Technology
    Excerpt

    Based on results of field testing conducted by the U.S. Department of Energy's National Energy Technology Laboratory (DOE/NETL), this article provides preliminary costs for mercury control via conventional activated carbon injection (ACI), brominated ACI, and conventional ACI coupled with the application of a sorbent enhancement additive (SEA) to coal prior to combustion. The economic analyses are reported on a plant-specific basis in terms of the cost required to achieve low (50%), mid (70%), and high (90%) levels of mercury removal "above and beyond" the baseline mercury removal achieved by existing emission control equipment. In other words, the levels of mercury control are directly attributable to ACI. Mercury control costs via ACI have been amortized on a current dollar basis. Using a 20-year book life, levelized costs for the incremental increase in cost of electricity (COE), expressed in mills per kilowatt-hour (mills/kWh), and the incremental cost of mercury control, expressed in dollars per pound of mercury removed ($/lb Hg removed), have been calculated for each level of ACI mercury control. For this analysis, the increase in COE varied from 0.14 mills/kWh to 3.92 mills/kWh. Meanwhile, the incremental cost of mercury control ranged from $3810/lb Hg removed to $166000/lb Hg removed.

    Title Gene Expression Profiling of Monocyte-derived Macrophages Following Infection with Mycobacterium Avium Subspecies Avium and Mycobacterium Avium Subspecies Paratuberculosis.
    Date February 2007
    Journal Physiological Genomics
    Excerpt

    Mycobacterium avium subspecies paratuberculosis (MAP) and Mycobacterium avium subspecies avium (MAA) represent two closely related intracellular bacteria with vastly different associated pathologies. MAA can cause severe respiratory infections in immune compromised humans but is nonpathogenic in ruminants and is more readily controlled by the bovine immune system than MAP. MAP causes a fatal wasting syndrome in ruminants, typified by granulomatous enteritis localized in the small intestine. MAP has also been cited as a potential cause of human Crohn's disease. We used a bovine immune-specific microarray (BOTL-5) to compare the response of mature bovine monocyte-derived macrophages (MDM cells) to MAP and MAA. Statistical analysis of microarray data revealed 21 genes not appreciably expressed in resting MDM cells that were activated following infection with either MAA or MAP. Further analysis revealed 144 genes differentially expressed in MDM cells following infection with MAA and 99 genes differentially expressed following infection with MAP. Of these genes, 37 were affected by both types of mycobacteria, with three being affected in opposite directions. Over 41% of the differentially expressed genes in MAA and MAP infected MDM cells were members of, regulated by, or regulators of the MAPK pathways. Expression of selected genes was validated by quantitative real-time reverse transcriptase PCR and in several key genes (i.e., IL-2 receptor, tissue inhibitor of matrix metalloproteinases-1, and Fas-ligand) MAA was found to be a stronger activating factor than MAP. These gene expression patterns were correlated with prolonged activation of p38 MAPK and ERK1/2 by MAA, relative to MAP.

    Title Watchful Waiting Vs Repair of Inguinal Hernia in Minimally Symptomatic Men: a Randomized Clinical Trial.
    Date January 2006
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    CONTEXT: Many men with inguinal hernia have minimal symptoms. Whether deferring surgical repair is a safe and acceptable option has not been assessed. OBJECTIVE: To compare pain and the physical component score (PCS) of the Short Form-36 Version 2 survey at 2 years in men with minimally symptomatic inguinal hernias treated with watchful waiting or surgical repair. DESIGN, SETTING, AND PARTICIPANTS: Randomized trial conducted January 1, 1999, through December 31, 2004, at 5 North American centers and enrolling 720 men (364 watchful waiting, 356 surgical repair) followed up for 2 to 4.5 years. INTERVENTIONS: Watchful-waiting patients were followed up at 6 months and annually and watched for hernia symptoms; repair patients received standard open tension-free repair and were followed up at 3 and 6 months and annually. MAIN OUTCOME MEASURES: Pain and discomfort interfering with usual activities at 2 years and change in PCS from baseline to 2 years. Secondary outcomes were complications, patient-reported pain, functional status, activity levels, and satisfaction with care. RESULTS: Primary intention-to-treat outcomes were similar at 2 years for watchful waiting vs surgical repair: pain limiting activities (5.1% vs 2.2%, respectively; P = .06 [corrected]); PCS (improvement over baseline, 0.29 points vs 0.13 points; P = .79). Twenty-three percent of patients assigned to watchful waiting crossed over to receive surgical repair (increase in hernia-related pain was the most common reason offered); 17% assigned to receive repair crossed over to watchful waiting. Self-reported pain in watchful-waiting patients crossing over improved after repair. Occurrence of postoperative hernia-related complications was similar in patients who received repair as assigned and in watchful-waiting patients who crossed over. One watchful-waiting patient (0.3%) experienced acute hernia incarceration without strangulation within 2 years; a second had acute incarceration with bowel obstruction at 4 years, with a frequency of 1.8/1000 patient-years inclusive of patients followed up for as long as 4.5 years. CONCLUSIONS: Watchful waiting is an acceptable option for men with minimally symptomatic inguinal hernias. Delaying surgical repair until symptoms increase is safe because acute hernia incarcerations occur rarely.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00263250.

    Title Fascial Ultrasound for Evaluation of Anterior Abdominal Stab Wound Injury.
    Date January 2006
    Journal The Journal of Trauma
    Excerpt

    Local stab wound (SW) exploration to assess abdominal fascial integrity is a highly invasive procedure frequently performed under demanding circumstances in the Emergency Department (ED). We hypothesized ultrasound (U/S) may be useful in the detection of fascial defects resulting from anterior abdominal stab injury, eliminating the need for local wound exploration

    Title Thrombosis of Sirolimus-eluting Coronary Stent in the Postanesthesia Care Unit.
    Date October 2005
    Journal Anesthesia and Analgesia
    Excerpt

    A 44-yr-old woman with a drug-eluting coronary stent placement two weeks before surgery suffered a myocardial infarction in the postanesthesia care unit immediately after hysterectomy. She had missed only one dose of aspirin and clopidogrel preoperatively. Early recognition of subacute stent thrombosis and urgent percutaneous coronary intervention probably prevented her death. In this case report, we highlight perioperative coronary stent issues and discuss their implications.

    Title Smoke Inhalation Enhances Early Alveolar Leukocyte Responsiveness to Endotoxin.
    Date September 2005
    Journal The Journal of Trauma
    Excerpt

    Pulmonary dysfunction after smoke inhalation and thermal injury is associated with excessive morbidity and mortality. The purpose of this study was to evaluate alveolar leukocyte function after thermal injury and smoke inhalation.

    Title Potent Modulation of Intestinal Tumorigenesis in Apcmin/+ Mice by the Polyamine Catabolic Enzyme Spermidine/spermine N1-acetyltransferase.
    Date August 2005
    Journal Cancer Research
    Excerpt

    Intracellular polyamine pools are homeostatically maintained by processes involving biosynthesis, catabolism, and transport. Although most polyamine-based anticancer strategies target biosynthesis, we recently showed that activation of polyamine catabolism at the level of spermidine/spermine N(1)-acetyltransferase-1 (SSAT) suppresses tumor outgrowth in a mouse prostate cancer model. Herein, we examined the effects of differential SSAT expression on intestinal tumorigenesis in the Apc(Min/+) (MIN) mouse. When MIN mice were crossed with SSAT-overproducing transgenic mice, they developed 3- and 6-fold more adenomas in the small intestine and colon, respectively, than normal MIN mice. Despite accumulation of the SSAT product, N(1)-acetylspermidine, spermidine and spermine pools were only slightly decreased due to a huge compensatory increase in polyamine biosynthetic enzyme activities that gave rise to enhanced metabolic flux. When MIN mice were crossed with SSAT knock-out mice, they developed 75% fewer adenomas in the small intestine, suggesting that under basal conditions, SSAT contributes significantly to the MIN phenotype. Despite the loss in catabolic capability, tumor spermidine and spermine pools failed to increase significantly due to a compensatory decrease in biosynthetic enzyme activity giving rise to a reduced metabolic flux. Loss of heterozygosity at the Apc locus was observed in tumors from both SSAT-transgenic and -deficient MIN mice, indicating that loss of heterozygosity remained the predominant oncogenic mechanism. Based on these data, we propose a model in which SSAT expression alters flux through the polyamine pathway giving rise to metabolic events that promote tumorigenesis. The finding that deletion of SSAT reduces tumorigenesis suggests that small-molecule inhibition of the enzyme may represent a nontoxic prevention and/or treatment strategy for gastrointestinal cancers.

    Title Raltitrexed Increases Tumorigenesis As a Single Agent Yet Exhibits Anti-tumor Synergy with 5-fluorouracil in Apcmin/+ Mice.
    Date July 2005
    Journal Cancer Biology & Therapy
    Excerpt

    The thymidylate synthase (TS) inhibitors raltitrexed (RTX) and 5-fluorouracil (FUra) have shown promising anti-tumor activity in preclinical and clinical settings for the treatment of colorectal cancer. Though the effects of these two agents have been reasonably well-characterized in cell lines, knowledge of their modes of action in vivo is limited. Here, we utilize the Apc(Min/+) mouse, an animal model of intestinal tumorigenesis, to study the effects of RTX treatment alone and in combination with FUra. Rather surprisingly, RTX monotherapy resulted in a dose dependent 4-10-fold increase in tumor number. The majority of these adenomas (74-95%) were rather small (i.e., less than 1 mm in diameter) and exhibited loss of heterozygosity at the Apc locus, suggesting an increase in mutational events leading to tumor development. RTX augmented BrdU-labeling of crypt epithelial cells, and retarded the movement of these cells along the crypt-villus axis. Co-administration of FUra and RTX resulted in a significant reduction in tumor number compared to mice treated with either RTX or FUra alone (P < 0.0001). In addition, FUra abrogated the RTX-mediated increase in BrdU labeling. In all, the results show that RTX increases tumor burden in the Apc(Min/+) mouse, yet enhances the anti-tumor effect of FUra. This is the first illustration of in vivo synergy of RTX and FUra in a genetically predisposed animal model. Possible mechanisms underlying the current observations are discussed.

    Title Laparoscopic Marsupialization of a Giant Posttraumatic Splenic Cyst.
    Date March 2005
    Journal Jsls : Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons
    Excerpt

    Nonparasitic cysts are rare clinical lesions of the spleen. Causes include congenital malformations and trauma. Historically, management has entailed partial or total splenectomy using an open approach. Recently, laparoscopic approaches have been developed. In this report, we describe laparoscopic marsupialization of a giant splenic cyst (diameter > 15 cm).

    Title Complications of Major Aortic and Lower Extremity Vascular Surgery.
    Date February 2005
    Journal Seminars in Cardiothoracic and Vascular Anesthesia
    Excerpt

    Atheromatous disease and invasive intervention of the aortoiliac and distal arteries are common. Morbidity and mortality have been reduced through understanding and management of patient risk factors. Complications of this form of treatment affect all organ systems; mortality is most frequently caused by a cardiovascular complication (eg, myocardial infarction). Infection, leading to aortoenteric fistula is a dreaded complication, and paraplegia, though rare, is a devastating outcome. Multiorgan failure and death may result from a systemic inflammatory response syndrome. Vascular surgery for infrainguinal disease also has a significant cardiovascular complication rate. Resulting complications may affect all organs; loss of an extremity may occur. The first part of this article reviews perioperative and postoperative complications of open aortic repair and lower-extremity revascularization and addresses the issue of regional anesthesia for major vascular surgery. The second part reviews endovascular aortic repair (EVAR). EVAR is a new intervention that combines surgery and radiology. Complications of EVAR are similar to open repair, but early results suggest they may be less frequent. New technology leads to new complications; endoleaks, migration of the endoprosthesis, and surgical conversion are unique to EVAR. The benefits of EVAR may be less blood loss, shorter hospitalization, and less cardiovascular stress; the risks may be aneurysm recurrence, prolonged surveillance and repeated secondary procedures. The development of EVAR, the complications, and the anesthesia-related concerns of EVAR, including its use in management of acute abdominal aortic aneurysm are reviewed.

    Title Reactive Oxygen Species Mediate Endotoxin-induced Human Dermal Endothelial Nf-kappab Activation.
    Date July 2003
    Journal The Journal of Surgical Research
    Excerpt

    BACKGROUND: Microvascular endothelial cell "activation" by endotoxin is an early and critical phenomenon underlying organ dysfunction related to sepsis. Dermal endothelial cells contribute to many of the manifestations of septic shock, such as cutaneous interstitial edema and loss of peripheral vasomotor regulation. Human dermal endothelial cell activation by endotoxin (lipopolysaccharide [LPS]) is characterized by the generation of reactive oxygen species (ROS) that enhance nuclear translocation of the transcription factor kappa-B (NF-kappaB). METHODS: We tested our hypothesis by stimulating human dermal microvascular endothelial cells (HMEC.1) with endotoxin and assaying for endothelial generation of ROS and nuclear translocation of NF-kappaB subunits. HMEC.1 cultures were treated individually with LPS, hydrogen peroxide, or xanthine, xanthine oxidase, and ferrous sulfate (xanthine/XO/Fe(2+)). Nuclear proteins were isolated and consensus sequence binding was assessed by electrophoretic mobility shift assay (EMSA). 2',7'-Dichlorofluorescin diacetate and confocal microscopy were used to examine ROS production in LPS-stimulated HMEC.1. RESULTS: Nuclear translocation of the p65/p50 NF-kappaB heterodimer was detectable 30 min after stimulation with LPS alone or the xanthine/XO/Fe(2+) combination, but not with hydrogen peroxide. Antioxidant N-acetylcysteine (NAC) inhibited LPS-stimulated ROS production in HMEC.1. Antioxidant prior to or simultaneously with LPS exposure, but not following LPS, also prevented NF-kappaB activation. NAC was ineffective at inhibiting NF-kappaB translocation at increased LPS concentrations. CONCLUSIONS: Dermal endothelial cells, a microvascular cell type that may contribute to the systemic response to blood-borne endotoxemia, generate ROS in the absence of other inflammatory cells. These LPS-activated endothelial cells, in turn, rapidly translocate transcription factor NF-kappaB to cell nuclei, a process regulated in part by intracellular ROS.

    Title Zo-1 Redistribution and F-actin Stress Fiber Formation in Pulmonary Endothelial Cells After Thermal Injury.
    Date February 2003
    Journal The Journal of Trauma
    Excerpt

    In response to isolated inflammatory stimuli, changes in endothelial cell morphology that enhance paracellular flow of solutes result from F-actin stress fiber formation, myosin phosphorylation, and actin anchoring protein (ZO-1) modifications. We hypothesized that myosin light chain kinase inhibition would diminish burn-enhanced endothelial monolayer permeability by secondarily preventing F-actin and actin anchoring protein rearrangements.

    Title Human Coronary Endothelial Cell Activation by Endotoxin is Characterized by Nf-kappa B Activation and Tnf-alpha Synthesis.
    Date April 2002
    Journal Shock (augusta, Ga.)
    Excerpt

    Tumor necrosis factor-alpha (TNF-alpha), an early inflammatory mediator typically regulated by nuclear factor kappa B (NF-kappa B), plays a critical role in the development of cardiovascular dysfunction in sepsis. While several myocardial cell types synthesize TNF-alpha, the importance of the myocardial endothelium in sepsis-related cardiac cytokine production is unclear. To determine the role of the human coronary artery endothelial cell (HCA-EC) in the cytokine response to endotoxin we measured in vitro TNF-alpha synthesis, TNF-alpha mRNA, and the associated NF-kappa B response to LPS. To determine the magnitude of the HCA-EC response we assessed the TNF-alpha and NF-kappa B response to LPS in a human monocytic cell line (THP-1) as well. We observed an increase in supernatant TNF-alpha from LPS-stimulated HCA-EC (12 h) that was ablated by the proteosome inhibitor, ALLN (N-acetyl-Leu-Leu-norleucinal). Similarly, ALLN-sensitive TNF-alpha was produced by monocytes following LPS, although at concentrations 100-fold higher than HCA-EC. TNF-alpha mRNA from HCA-EC was detected at 60 min in LPS-stimulated cells, but not in unstimulated cells or cells pretreated with ALLN. NF-kappa B p50/p65 subunits were detectable in endothelial nuclear protein 60 min following LPS. In contrast, NF-kappa B subunits from monocytes were detected at 15 min. Also, while ALLN only attenuated endothelial NF-kappa B translocation, monocyte NF-kappa B translocation was completely inhibited. These data suggest endotoxin-stimulated human coronary endothelial cells express TNF-alpha, which is regulated in part by NF-kappa B activation, in a manner and degree distinct from human monocytes.

    Title Differential Activation of Coronary and Pulmonary Endothelial Cells by Thermal Injury.
    Date March 2002
    Journal Shock (augusta, Ga.)
    Excerpt

    Remote organ dysfunction during resuscitation of severe thermal injury is characterized by early, transient pulmonary insufficiency and cardiac contractile dysfunction. Thermal injury is typified by profound systemic alterations of endothelial immunological, vasoactive, and barrier functions. The unique location of this ubiquitous, fragile monolayer makes it vulnerable to circulating serum factors created at remote cutaneous wounds. We examined endothelial "activation" in 2 distinct cell types, human coronary and pulmonary endothelial cells (EC), after severe thermal injury. By using human serum isolated at specific times after thermal injury ("early" [2 h post-burn] or "late" [26 h post-burn]), the endothelial release of vasoactive mediators, ICAM-1 expression, and monolayer permeability were assessed in vitro. Early burn serum enhanced coronary EC vasoconstrictor (ET-1) release and ICAM expression, inhibited vasodilator (PGI2) release, but had no effect on permeability. Conversely, under similar conditions, pulmonary EC PGI2 release and permeability were enhanced, ET-1 release was diminished, but ICAM was unaffected. Late burn serum enhanced vasodilator (NO) release and permeability to albumin in both coronary and pulmonary EC, whereas ET-1 release was inhibited. Under these conditions, only pulmonary ICAM expression was significantly enhanced. These data suggest that human endothelium isolated from divergent vascular beds are activated by burn injury in a unique manner for time post-burn and vascular site of cell origin.

    Title Colorimetric Assay to Quantify Macromolecule Diffusion Across Endothelial Monolayers.
    Date February 2002
    Journal Biotechniques
    Excerpt

    Endothelial "capillary leak", the loss of vascular integrity in response to noxious stimuli, is characterized by extravasation of protein-richfluidfrom capillary lumen into surrounding tissue interstitium. This increase in vascular permeability, in response to inflammatory mediators, correlates with endothelial cell contraction and the formation of intercellular gaps within the monolayer. However, in vivo assessment of paracellular solute flow between endothelial cells may be complicated by multiple uncontrolled parameters. In vitro examinations of endothelial barrier leak have relied on electrical impedence or macromolecule diffusion techniques to determine the details pertinent to capillary barrier function. In this report, a simple, sensitive, nonradioactive, colorimetric assay to quantify the leak of a labeled protein marker across endothelial monolayers is described. This procedure avoids the hazards of radioisotope labels and the technical limitations of electrical resistance technology.

    Title Recombinant Phycobiliproteins. Recombinant C-phycocyanins Equipped with Affinity Tags, Oligomerization, and Biospecific Recognition Domains.
    Date May 2001
    Journal Analytical Biochemistry
    Excerpt

    A family of specific cloning vectors was constructed to express in the cyanobacterium Anabaena sp. PCC7120 recombinant C-phycocyanin subunits with one or more different tags, including the 6xHis tag, oligomerization domains, and the streptavidin-binding Strep2 tag. Such tagged alpha or beta subunits of Anabaena sp. PCC7120 C-phycocyanin formed stoichiometric complexes in vivo with appropriate wild-type subunits to give constructs with the appropriate oligomerization state and normal posttranslational modifications and with spectroscopic properties very similar to those of unmodified phycocyanin. All of these constructs were incorporated in vivo into the rod substructures of the light-harvesting complex, the phycobilisome. The C-terminal 114-residue portion of the Anabaena sp. PCC7120 biotin carboxyl carrier protein (BCCP114) was cloned and overexpressed and was biotinylated up to 20% in Escherichia coli and 40% in wild-type Anabaena sp. His-tagged phycocyanin beta--BCCP114 constructs expressed in Anabaena sp. were >30% biotinylated. In such recombinant phycocyanins equipped with stable trimerization domains, >75% of the fusion protein was specifically bound to streptavidin- or avidin-coated beads. Thus, the methods described here achieve in vivo production of stable oligomeric phycobiliprotein constructs equipped with affinity purification tags and biospecific recognition domains usable as fluorescent labels without further chemical manipulation.

    Title Thrombin-mediated Permeability of Human Microvascular Pulmonary Endothelial Cells is Calcium Dependent.
    Date April 2001
    Journal The Journal of Trauma
    Excerpt

    In response to inflammation, endothelial cytoskeleton rearrangement, cell contraction, and intercellular gap formation contribute to a loss of capillary barrier integrity and resultant interstitial edema formation. The intracellular signals controlling these events are thought to be dependent on intracellular calcium concentration ([Ca2+]i). We hypothesized that, in human pulmonary microvascular endothelial cells, a thrombin-induced increase in permeability to albumin would be dependent on Ca2+i and subsequent actin cytoskeleton rearrangements.

    Title Thermal Injury Alters Myocardial Sarcoplasmic Reticulum Calcium Channel Function.
    Date July 2000
    Journal The Journal of Surgical Research
    Excerpt

    We have previously shown that a major cutaneous thermal injury produces profound cardiac contractile dysfunction despite adequate resuscitation. While the molecular basis of this dysfunction is unknown, recent work has suggested that alterations in calcium flux between the myocyte sarcoplasmic reticulum (SR) to the cytoplasm may play a role.

    Title Probing the Photoreaction Mechanism of Phytochrome Through Analysis of Resonance Raman Vibrational Spectra of Recombinant Analogues.
    Date April 2000
    Journal Biochemistry
    Excerpt

    Resonance Raman spectra of native and recombinant analogues of oat phytochrome have been obtained and analyzed in conjunction with normal mode calculations. On the basis of frequency shifts observed upon methine bridge deuteration and vinyl and C(15)-methine bridge saturation of the chromophore, intense Raman lines at 805 and 814 cm(-)(1) in P(r) and P(fr), respectively, are assigned as C(15)-hydrogen out-of-plane (HOOP) wags, lines at 665 cm(-)(1) in P(r) and at 672 and 654 cm(-)(1) in P(fr) are assigned as coupled C=C and C-C torsions and in-plane ring twisting modes, and modes at approximately 1300 cm(-)(1) in P(r) are coupled N-H and C-H rocking modes. The empirical assignments and normal mode calculations support proposals that the chromophore structures in P(r) and P(fr) are C(15)-Z,syn and C(15)-E,anti, respectively. The intensities of the C(15)-hydrogen out-of-plane, C=C and C-C torsional, and in-plane ring modes in both P(r) and P(fr) suggest that the initial photochemistry involves simultaneous bond rotations at the C(15)-methine bridge coupled to C(15)-H wagging and D-ring rotation. The strong nonbonded interactions of the C- and D-ring methyl groups in the C(15)-E,anti P(fr) chromophore structure indicated by the intense 814 cm(-1) C(15) HOOP mode suggest that the excited state of P(fr) and its photoproduct states are strongly coupled.

    Title Cardiovascular Effect of 7.5% Sodium Chloride-dextran Infusion After Thermal Injury.
    Date November 1999
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    Clinical study can help determine the safety and cardiovascular and systemic effects of an early infusion of 7.5% sodium chloride in 6% dextran-70 (hypertonic saline-dextran-70 [HSD]) given as an adjuvant to a standard resuscitation with lactated Ringer (RL) solution following severe thermal injury.

    Title Thermal Injury Alters Endothelial Vasoconstrictor and Vasodilator Response to Endotoxin.
    Date October 1999
    Journal The Journal of Trauma
    Excerpt

    The unique location of the endothelium makes it vulnerable to injury from circulating factors created at remote wounds. In this study, we examined the effect of a sequential burn and lipopolysaccharide (LPS) challenge on endothelial function in vitro.

    Title Preconditioning Prevents Myocardial Stunning After Cardiac Transplantation.
    Date February 1999
    Journal The Annals of Thoracic Surgery
    Excerpt

    Preconditioning has been shown to reduce myocardial stunning after reversible global ischemia. To determine whether preconditioning improves functional recovery after cardiac transplantation, 16 sheep were randomly assigned to a preconditioning protocol or to a control group.

    Title Prescribing Alcohol in a General Hospital: 'not Everything in Black and White Makes Sense'.
    Date December 1998
    Journal Journal of the Royal College of Physicians of London
    Excerpt

    The policies and practicalities of prescribing alcohol for inpatients at a teaching hospital were examined. Sources of information easily available to hospital medical staff were searched for guidance on the prescription of alcohol. No guidance relevant to clinical practice was found. Current practice in a single hospital was examined using a semistructured staff interview. While nurses and doctors suggested a wide range of indications for prescribing alcohol, most of these are not supported by evidence and for some, such as alcoholism and depression, alcohol would be contra-indicated. The persistence of alcohol prescribing in hospital is based on tradition rather than evidence of its effectiveness. It sends an undesirable message to patients who may be suffering from alcohol-related medical disorders, and it is time to discontinue this outdated clinical practice.

    Title Evaluation of Troponin-i As an Indicator of Cardiac Dysfunction After Thermal Injury.
    Date October 1998
    Journal The Journal of Trauma
    Excerpt

    Biochemical serum markers commonly used to assess human cardiac injury (creatinine phosphokinase, creatine phosphokinase-MB) have been shown to have diminished specificity for detection of cardiac injury in the setting of burn-related soft-tissue and skeletal muscle injury. Laboratory studies have demonstrated that severe cutaneous thermal injury is associated with cardiac contractile dysfunction and a corresponding elevation in serum cardiac troponin-I (cTn-I) in several species.

    Title The Phytofluors: a New Class of Fluorescent Protein Probes.
    Date February 1998
    Journal Current Biology : Cb
    Excerpt

    Biologically compatible fluorescent protein probes, particularly the self-assembling green fluorescent protein (GFP) from the jellyfish Aequorea victoria, have revolutionized research in cell, molecular and developmental biology because they allow visualization of biochemical events in living cells. Additional fluorescent proteins that could be reconstituted in vivo while extending the useful wavelength range towards the orange and red regions of the light spectrum would increase the range of applications currently available with fluorescent protein probes.

    Title Light Versus Heavy Sedation After Cardiac Surgery: Myocardial Ischemia and the Stress Response. Maritime Heart Centre and Dalhousie University.
    Date November 1997
    Journal Anesthesia and Analgesia
    Excerpt

    The influence of light versus heavy sedation after coronary artery bypass graft (CABG) surgery on the development of postoperative myocardial ischemia has not been described. After uncomplicated CABG surgery, 50 patients were randomly assigned to receive LOW (n = 24; target Ramsay Sedation Score [RSS] = 2) or HIGH (n = 26; target RSS = 4) sedation with propofol. Analgesia was provided to maintain a visual analog scale (VAS) pain score <7. Myocardial ischemia was identified perioperatively using continuous 3-lead Holter monitoring. By measuring creatine kinase (CK) MB levels preoperatively, at entry to the intensive care unit (ICU), and every 12 h for 48 h; and by obtaining serial 12-lead electrocardiograms (ECG) (preoperatively; 2, 4, 12, 24, and 48 h after ICU admission, 8:00 AM the morning after surgery; and 5 min pre- and postextubation), myocardial infarction was identified. Endocrine stress response was assessed by measuring serum cortisol levels preoperatively, on admission to the ICU, and 24 h postoperatively. In a subset of patients (LOW n = 10, HIGH n = 11), plasma and urinary catecholamine levels were also measured. There were no between-group differences in demographics, operative course, hemodynamic variables, or cortisol levels while in the ICU. The VAS pain score and target RSS were achieved and sustained, and they differed between groups. There were three myocardial infarctions in each group by CKMB criteria alone. No ECG-identifiable myocardial infarction occurred. The ST segment versus time curve (LOW 187 +/- 295 versus HIGH 1071 +/- 2137 mm/min) differed between groups. Urinary and plasma catecholamine levels were similar between groups over the observation period. We conclude that the use of a reduced sedation regimen in combination with adequate analgesia did not result in an increased endocrine stress response or risk of myocardial ischemia. IMPLICATIONS: This randomized study of patients after coronary artery bypass surgery examined whether light (versus heavy) sedation with propofol in the intensive care unit was associated with an increased degree of myocardial ischemia. Using techniques to detect myocardial ischemia, including Holter monitoring, electrocardiogram, and myocardial enzyme measurements, no differences were found. We conclude that light sedation does not increase the endocrine stress response or the risk of myocardial infarction.

    Title Redefining the Growth of the Heterosexual Hiv/aids Epidemic in Chicago.
    Date November 1997
    Journal Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association
    Excerpt

    A dramatic shift in the relative distribution of the five categories of heterosexual transmission for AIDS cases diagnosed in Chicago since 1991 prompted a mode-of-transmission validation study of what had become the most frequently reported heterosexual exposure: heterosexual relations with a person with AIDS (PWA) or documented HIV infection whose risk is not specified.

    Title Toxic Epidermal Necrolysis.
    Date October 1997
    Journal The Journal of Burn Care & Rehabilitation
    Excerpt

    Toxic epidermal necrolysis (TEN) is a poorly understood and devastating condition. It is usually diagnosed in a primary care setting. Treatment of severe cases by burn care personnel is usually by referral. In this review, we report excessive mortality rates associated with prolonged use of systemic steroid therapy and delayed referral (more than 1 week from diagnosis). Forty-four consecutive patients admitted to a regional burn center with the diagnosis of TEN over a 14-year period, (0.7% of all admissions) were included. Precipitating factors were identified in 30 cases. Twenty-one patients had known prehospital allergy conditions directly related to the inciting agent. The mean age of this population was 44.9 years, and the mean total body surface area (TBSA) injury was 52.4%. Eighty-four and one-half percent of all patients with TEN were admitted to the ICU. Twenty-four patients required ventilator support. Overall mortality rate was 36%. Nonsurviving patients had a mean age of 61.6 years, compared to 35.3 years for survivors. Nonsurvivors had a mean TBSA of 64.4%, survivors had a mean TBSA of 44%. TEN, although a nonthermal injury, is best managed by personnel experienced in the care of severe thermal injuries. Despite the availability of this expertise, delayed transfer of severe presentations continues to contribute to exceptionally high morbidity and mortality rates.

    Title A Cyanobacterial Phytochrome Two-component Light Sensory System.
    Date September 1997
    Journal Science (new York, N.y.)
    Excerpt

    The biliprotein phytochrome regulates plant growth and developmental responses to the ambient light environment through an unknown mechanism. Biochemical analyses demonstrate that phytochrome is an ancient molecule that evolved from a more compact light sensor in cyanobacteria. The cyanobacterial phytochrome Cph1 is a light-regulated histidine kinase that mediates red, far-red reversible phosphorylation of a small response regulator, Rcp1 (response regulator for cyanobacterial phytochrome), encoded by the adjacent gene, thus implicating protein phosphorylation-dephosphorylation in the initial step of light signal transduction by phytochrome.

    Title Two New Lignans with Activity Against Influenza Virus from the Medicinal Plant Rhinacanthus Nasutus.
    Date September 1997
    Journal Journal of Natural Products
    Excerpt

    Two new lignans, rhinacanthin E (1) and rhinacanthin F (2), were isolated from the aerial parts of the plant Rhinacanthus nasutus. Their structures were established by detailed spectroscopic analysis. These compounds show significant antiviral activity against influenza virus type A.

    Title The Use of Low-dose Aprotinin, Epsilon-aminocaproic Acid or Tranexamic Acid for Prevention of Mediastinal Bleeding in Patients Receiving Aspirin Before Coronary Artery Bypass Operations.
    Date July 1997
    Journal European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery
    Excerpt

    Patients undergoing primary myocardial revascularization were randomized to one of three drug regimens (low-dose aprotinin, epsilon-aminocaproic Acid or tranexamic Acid) to determine which drug regimen would most effectively reduce post-operative bleeding and the need for blood products. All patients had received 325 mg of aspirin within 48 h before operation. All three drug regimens reduced the requirements for blood products and postoperative bleeding after coronary artery bypass operations. There was, however, no significant difference between drug regimens.

    Title Purification and Characterization of Recombinant Affinity Peptide-tagged Oat Phytochrome A.
    Date May 1997
    Journal Photochemistry and Photobiology
    Excerpt

    Full-length Avena sativa (oat) phytochrome A (ASPHYA) was expressed in the yeast Saccharomyces cerevisiae and purified to apparent homogeneity. Expression of an ASPHYA cDNA that encoded the full-length photoreceptor with a 15 amino acid 'strep-tag' peptide at its C-terminus produced a single polypeptide with a molecular mass of 124 kDa. This strep-tagged polypeptide (ASPHYA-ST) bound tightly to streptavidin agarose and was selectively eluted using diaminobiotin, with a chromatographic efficiency of 45%. Incubation of ASPHYA-ST with phytochromobilin (P phi B) and the unnatural chromophore precursors, phycocyanobilin (PCB) and phycoerythrobilin (PEB), produced covalent adducts that were similarly affinity purified. Both P phi B and PCB adducts of ASPHYA-ST were photoactive--the P phi B adduct displaying spectrophotometric properties nearly indistinguishable from those of the native photoreceptor, and the PCB adduct exhibiting blue-shifted absorption maxima. Although the PEB adduct of ASPHYA-ST was photochemically inactive, it was intensely fluorescent with an excitation maximum at 576 nm and emission maxima at 586 nm. The superimposability of its absorption and fluorescence excitation spectra established that a single biliprotein species was responsible for fluorescence from the adduct produced when ASPHYA-ST was incubated with PEB. Steric exclusion HPLC also confirmed that ASPHYA-ST and its three bilin adducts were homodimers, as has been established for phytochrome A isolated from natural sources. The ability to express and purify recombinant phytochromes with biochemical properties very similar to those of the native molecule should facilitate detailed structural analysis of this important class of photoreceptors.

    Title Randomized Trial Comparing Intermittent Antegrade Warm Blood Cardioplegia with Multidose Cold Blood Cardioplegia for Coronary Artery Bypass.
    Date August 1996
    Journal European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery
    Excerpt

    Forty patients were randomized to receive antegrade multidose warm (WBC) or cold blood cardioplegia (CBC) during coronary artery bypass. Cardioplegia was infused at a predetermined dose every 10 min during cardioplegia arrest and core temperature was maintained at 37 degrees C in both groups during extracorporeal circulation. Patient profiles were similar in the two groups. Cardiac index, left ventricular stroke work index, and myocardial oxygen consumption were measured before bypass and during the first 7 h of reperfusion. There was no significant difference in myocardial metabolic and function recovery, the incidence of myocardial infarction, low cardiac output or death. Our data suggests that similar protection is provided with the two techniques of myocardial protection.

    Title Renal Autotransplantation After Horseshoe Kidney Injury: a Case Report and Literature Review.
    Date June 1996
    Journal The Journal of Trauma
    Excerpt

    We present a patient with lap seatbelt trauma to a previously unsuspected horseshoe kidney. Preoperative single film intravenous pyelography did not suggest the presence of this renal anomaly or define the extent of renal injury. Because of the severity of the injury, nephrectomy was life-saving, but inadvertently rendered the patient anephric. Recognition of horseshoe kidney anatomy, microvascular back-bench reconstruction, and renal autotransplantation allowed the salvage of both the patient and her renal function.

    Title Continuous Fluorescence Assay of Phytochrome Assembly in Vitro.
    Date August 1995
    Journal Biochemistry
    Excerpt

    Incubation of recombinant apophytochrome with the phycobiliprotein chromophore precursor phycoerythrobilin produces a covalent adduct that exhibits a fluorescence excitation maximum at 576 nm and an emission maximum at 586 nm. Using these fluorescence parameters, we have developed a kinetic assay for quantitative analysis of the assembly of the plant photoreceptor phytochrome in real time. Kinetic measurements performed with different phycoerythrobilin concentrations confirm that bilin attachment to apophytochrome involves two steps, an initial formation of a reversible non-covalent complex followed by thioether bond formation. The kinetic constants for both steps of phycoerythrobilin attachment to apophytochrome were estimated with this assay. Methodology for determining the kinetic constants for the assembly of both the natural phytochrome chromophore precursor, phytochromobilin, and the analog phycocyanobilin is also described. Since the latter two bilins yield covalent, nonfluorescent adducts with apophytochrome, their co-incubation with phycoerythrobilin reduces the rate of formation of the fluorescent phycoerythrobilin adduct in an irreversible, competitive manner. Competition experiments were also performed with biliverdin, a structurally related bilin which does not form a covalent adduct with apophytochrome. Such measurements show that biliverdin reversibly binds to apophytochrome with a submicromolar binding constant, an affinity which is very similar to that of phytochromobilin. The utility of this fluorescence assay for identification of novel inhibitors of phytochrome assembly and for characterization of the structural features of both bilin and apophytochrome necessary for photoreceptor assembly is discussed.

    Title Pediatric Grease Burn Injury.
    Date June 1995
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    To evaluate the incidence and severity of grease and oil burns in children and to discuss prevention.

    Title Myocardial Metabolic and Hemodynamic Changes During Propofol Anesthesia for Cardiac Surgery in Patients with Reduced Ventricular Function.
    Date October 1993
    Journal Anesthesia and Analgesia
    Excerpt

    This study examined the hypothesis that the use of propofol for induction and maintenance of anesthesia in patients with reduced ejection fraction (< 0.5) undergoing coronary artery revascularization would not be associated with a greater degree or incidence of myocardial ischemia as compared to patients receiving a moderate dose sufentanil-enflurane anesthetic technique. Two groups of patients were assigned randomly to receive one of two propofol anesthetic regimes. Group A (n = 21) received propofol 1-2 mg/kg as the induction drug and sufentanil 0.03 micrograms.kg-1.min-1 (fixed rate) plus propofol 50-200 micrograms.kg-1.min-1 (variable rate) infusions for maintenance of anesthesia. Group B (n = 21) received sufentanil 5 micrograms/kg for induction and propofol 50-200 micrograms.kg-1.min-1 (variable rate) infusion for maintenance of anesthesia. For comparison, a third group (Group C, n = 18) was studied subsequently. This group received sufentanil 5 micrograms/kg for induction of anesthesia which was maintained with enflurane. Adverse hemodynamic changes (hypertension, tachycardia) were managed by additional propofol (Groups A and B), sufentanil (Group C), or vasopressors (hypotension). Hemodynamic and myocardial metabolic profiles were measured when awake and sedated and at postinduction, postintubation, postincision, poststernotomy, and precardiopulmonary bypass times. Ischemia was assessed by measuring myocardial lactate production. The incidence of myocardial lactate production was reduced in Group B as compared to Group C (Group A, 45/126; Group B, 23/126; Group C, 58/107; P < 0.05). Myocardial lactate flux declined in all groups as surgery progressed; but apart from the reduction in flux (indicative of increased ischemia) noted in Group C versus Group B postinduction, no between-group differences were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title A Comparison of the Myocardial Metabolic and Haemodynamic Changes Produced by Propofol-sufentanil and Enflurane-sufentanil Anaesthesia for Patients Having Coronary Artery Bypass Graft Surgery.
    Date January 1992
    Journal Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie
    Excerpt

    The purpose of this study was to compare propofol-sufentanil with enflurane-sufentanil anaesthesia for patients undergoing elective coronary artery bypass graft (CABG) surgery with respect to changes in (1) haemodynamic variables; (2) myocardial blood flow and metabolism; (3) serum cortisol, triglyceride, lipoprotein concentrations and liver function; and (4) recovery characteristics. Forty-seven patients with preserved ventricular function (ejection fraction greater than 40%, left ventricular end diastolic pressure less than or equal to 16 mmHg) were studied. Patients in Group A (n = 24) received sufentanil 0.2 microgram.kg-1 and propofol 1-2 mg.kg-1 for induction of anaesthesia which was maintained with a variable rate propofol (50-200 micrograms.kg-1.min-1) infusion and supplemental sufentanil (maximum total 5 micrograms.kg-1). Patients in Group B (n = 23) received sufentanil 5 micrograms.kg-1 for induction of anaesthesia which was maintained with enflurane and supplemental sufentanil (maximum total 7 micrograms.kg-1). Haemodynamic and myocardial metabolic profiles were determined at the awake-sedated, post-induction, post-intubation, first skin incision, post-sternotomy, and pre-cardiopulmonary bypass intervals. Induction of anaesthesia produced a larger reduction in systolic blood pressure in Group A (156 +/- 22 to 104 +/- 20 mmHg vs 152 +/- 26 to 124 +/- 24 mmHg; P less than 0.05). No statistical differences were detected at any other time or in any other variable including myocardial lactate production (n = 13 events in each group), time to tracheal extubation and time to discharge from the ICU. We concluded that, apart from hypotension on induction of anaesthesia, propofol-sufentanil anaesthesia produced anaesthetic conditions equivalent to enflurane-sufentanil anaesthesia for CABG surgery.

    Title Single Unit Analysis of the Human Ventral Thalamic Nuclear Group. Activity Correlated with Movement.
    Date February 1991
    Journal Brain : a Journal of Neurology
    Excerpt

    During neurosurgical operations for the relief of movement disorders, single thalamic neurons (n = 107) were identified with activity which was related to verbally cued active movements (movement-related cells). The activity of each neuron was examined during different contralateral movements in order to determine the movement which was associated with the most consistent and pronounced change in firing rate (the optimal response). The optimal response was determined by analysis of histograms of neuronal activity which were constructed by using the onset of EMG activity to synchronize successive repetitions of the active movement. Movement-related cells exhibited optimal responses associated with such movements as making a fist, extension or flexion of the wrist, flexing or extending the elbow, pointing with the entire upper extremity, extending the tongue and lifting the leg. Most movement-related cells recorded in a single parasagittal plane in an individual patient had optimal responses related to movements involving the same part of the body. Movement-related cells were classified into those that were activated in response to somatosensory stimulation (combined cells, n = 20) and those which were not (voluntary cells, n = 87). Combined cells were activated in advance of EMG activity during active movement and so could be distinguished from cells responding only to sensory stimulation (sensory cells). Movement-related cells (combined and voluntary cell types) were located anterior to sensory cells and tended to show a mediolateral somatotopic organization parallel to that of sensory cells with cutaneous receptive fields. Combined cells responded to somatosensory stimulation of the same part of the body as that involved in the active movement related to the optimal response of the cell. Combined cells responding to passive movements of a joint always had their optimal response during active movement about the same joint. The activity of combined cells during parkinsonian tremor may clarify the role of sensory feedback in tremor.

    Title A Randomized Study of Changes in Serum Cholesterol, Triglycerides, High Density Lipoproteins, and Cortisol During Cardiac Surgery in Patients Anaesthetised with Propofol-sufentanil Vs Enflurane-sufentanil. Cardiac Anaesthesia Research Group.
    Date August 1990
    Journal Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie
    Title Binding of Transcription Factors to the Promoter of the Human U1 Rna Gene Studied by Footprinting.
    Date December 1988
    Journal The Journal of Biological Chemistry
    Excerpt

    The promoter structure of the known small nuclear RNA (snRNA) genes contains two major effectors of transcriptional activity: a proximal sequence element and a distal sequence element. In addition to these two functional elements (called elements B and D), the human U1 snRNA gene contains at least three minor elements (elements A, C, and E) that contribute to overall transcriptional efficiency (Murphy, J.T., Skuzeski, J.M., Lund, E., Steinberg, T.H., Burgess, R.R., and Dahlberg, J.E. (1987) J. Biol. Chem. 262, 1795-1803). To elucidate further the function of these transcription elements, we carried out a computer search to look for sequences in the U1 gene homologous to known transcription factor consensus sequences. Where such homology was found, DNase I and MPE-Fe(II) (methidiumpropyl-EDTA-Fe(II] footprinting was employed to study the interactions of these promoter regions with proteins partially purified from extracts of HeLa cells or human placenta. Footprints were observed over element D (the distal element) corresponding to sequences homologous to the octanucleotide binding protein (OCTA) and activator protein 1 (AP1). Protection was also observed over element B (the proximal element) corresponding to possible sites for stimulatory protein 1 (Sp1), enhancer core, major late transcription factor (MLTF), and a U1-specific transcription factor. Prior to this study, no specific transcription factor footprints had been observed over proximal elements of any snRNA gene. Footprints were also found over elements A and E. The results of the computer search and the footprinting are discussed in light of what is known about snRNA promoter activity.

    Title Selection of the Optimal Lesion Site for the Relief of Parkinsonian Tremor on the Basis of Spectral Analysis of Neuronal Firing Patterns.
    Date June 1988
    Journal Applied Neurophysiology
    Excerpt

    Techniques for quantitatively describing the firing properties of neurons have been used to identify thalamic cells with a firing pattern which is correlated with EMG activity during tremor. By locating these cells relative to the anterior border of the somatosensory nucleus and the anterior commissure-posterior commissure line, it may be possible to select the optimal lesion site for the relief of parkinsonian tremor on a rational rather than an empirical basis.

    Title Single-unit Analysis of the Human Ventral Thalamic Nuclear Group: Somatosensory Responses.
    Date May 1988
    Journal Journal of Neurophysiology
    Excerpt

    1. We have studied the functional and somatotopic properties of 531 single mechanoreceptive thalamic neurons in humans undergoing stereotactic surgery for the control of movement disorders and pain. The majority of these somatosensory cells had small receptive fields (RFs) and were activated in a reproducible manner by mechanical stimuli applied to the skin or deep tissues. These neurons, which we termed "lemniscal," could be further classified into those responding to stimulation of cutaneous (76% of lemniscal sensory cells) or deep (24%) structures. 2. The incidence of neurons having cutaneous or mucosal RFs in the perioral region, thumb, and fingers (66%) was much higher than that of neurons having RFs elsewhere on the body. Most of the deep cells were activated by movements of and/or mechanical stimuli delivered to muscles or tendons controlling the elbow, wrist, and fingers. 3. Sequences of cells spanning several millimeters in the parasagittal plane often exhibited overlapping RFs. However, RFs changed markedly for cells separated by the same distances in the mediolateral direction. This suggests that the cutaneous somatotopic representation of each region of the body is organized into relatively thin sheets of cells oriented in the parasagittal plane. 4. By comparing neuronal RFs in different parasagittal planes in thalamus of individual patients we have identified a mediolateral representation of body surface following the sequence from: intraoral structures, face, thumb through fifth finger to palm, with forearm and leg laterally. 5. Along many trajectories in the parasagittal plane the sequence of cells with overlapping RFs was interrupted by another sequence of cells with RFs corresponding to a different body region. The RFs of the intervening sequence characteristically represented body regions known to be located more medially in thalamus (see 3 above). These findings could be explained if the lamellae postulated above were laterally convex. 6. Cells responding to deep stimulation (deep cells) could be further classified into those responding to joint movement (63%), deep pressure (15%), or both (22%). Deep cells were found usually at the anterior-dorsal border and sometimes at the posterior border of the region containing cells responding to cutaneous stimuli. Although there was some overlap in the RFs, deep cells representing wrist were found medial to those representing elbow, and both of these were found medial to cells representing leg.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Methods for Microstimulation and Recording of Single Neurons and Evoked Potentials in the Human Central Nervous System.
    Date April 1988
    Journal Journal of Neurosurgery
    Excerpt

    An apparatus and technique are described for microstimulation and recording of both slow wave and single neuron (single unit) activities during functional stereotaxic procedures. This method facilitates microstimulation and evoked potential and single unit analysis which, in combination, provide optimum definition of stereotaxic targets in the treatment of functional disorders of the human central nervous system.

    Title Single Unit Analysis of the Human Ventral Thalamic Nuclear Group: Correlation of Thalamic "tremor Cells" with the 3-6 Hz Component of Parkinsonian Tremor.
    Date April 1988
    Journal The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
    Excerpt

    Although cells firing at tremor frequency, called "tremor cells" (Guiot et al., 1962), have often been recorded in the thalamus of parkinsonian patients, the extent of correlation between these spike trains and tremor has rarely been assessed quantitatively. This paper describes spectral cross-correlation functions calculated between the activity of "tremor cells" and electromyogram (EMG) signals recorded from several muscles in the contralateral arm. The power occurring in the spike train at tremor frequency was described in absolute terms by the spike autopower, and in relation to the average for all spectral components by the spike autopower signal-to-noise ratio (spike autopower SNR). The probability of significant cross-correlation between the thalamic spike train and EMG at tremor frequency was assessed by the coherence at tremor frequency. Autopower spectra of the activity of many of these cells exhibited a concentration of power at tremor frequency, indicated by spike autopower SNRs as high as 18. Of the EMG signals studied, signals recorded from finger flexors were most often significantly correlated at tremor frequency. Significant correlation between the thalamic spike train and finger flexor EMG activity was found in 34% of cells analyzed. Tremor frequency coherence was significantly correlated with tremor frequency spike autopower (r = 0.46, p less than 0.0001) and spike autopower SNR (r = 0.533, p less than 0.0001). The proportion of cells with a spike autopower SNR greater than 2 that were significantly correlated with finger flexor EMG activity was greater than that of cells with a spike autopower SNR of less than 2 (p less than 0.001; chi-square). Therefore, cells exhibiting a large amount of power at tremor frequency were those best correlated with EMG activity during tremor. Some of these cells may be involved in the generation of tremor.

    Title A Neurophysiologic Approach to Functional Prognosis in Brain Damage.
    Date March 1988
    Journal Electromyography and Clinical Neurophysiology
    Title Abnormal Single-unit Activity Recorded in the Somatosensory Thalamus of a Quadriplegic Patient with Central Pain.
    Date March 1988
    Journal Pain
    Excerpt

    We have performed single unit analysis of the activity of cells located in the ventral nuclear group of thalamus in a patient with dysesthetic pain below the level of a clinically complete traumatic spinal cord transection at C5. Cells located in the parasagittal plane 14 mm lateral to the midline responded to tactile stimulation in small facial and intraoral receptive fields, which were characteristic of patients without somatosensory abnormality [30]. In this patient the 16 mm lateral parasagittal plane contained cells with receptive fields located on the occiput and neck instead of the upper extremity as would normally be expected. Cells with receptive fields on the neck and occiput had not previously been observed in recordings from single units (n = 531) responding to somatosensory stimulation [30]. Thus, on the basis of their location in a region of thalamus which normally represents parts of the body below the level of the spinal cord transection and their unusual receptive fields adjacent to these same parts of the body, we propose that the cells in the 16 mm lateral plane have lost their normal afferent input. Analysis of the autopower spectra of spike trains indicates that cells in the 16 mm lateral plane exhibited a higher mean firing rate and greater tendency to fire in bursts than cells in the 14 mm lateral plane (P less than 0.005). Finally, electrical stimulation at the recording sites in the 16 mm lateral plane evoked a burning sensation in the occiput, neck and upper extremity. These results suggest that regions of thalamus which have lost their normal somatosensory input contain neurons which exhibit abnormal spontaneous and evoked activity and that electrical stimulation of these regions can produce the sensation of burning dysesthesia.

    Title The Role of Feedback in the Tremor Frequency Activity of Tremor Cells in the Ventral Nuclear Group of Human Thalamus.
    Date December 1987
    Journal Acta Neurochirurgica. Supplementum
    Excerpt

    Close loop system identification techniques have been used to identify the presence of feedback in the firing pattern of thalamic tremor cells recorded in parkinsonian tremor patients.

    Title Adult Onset Systemic Carnitine Deficiency: Favorable Response to L-carnitine Supplementation.
    Date April 1987
    Journal The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques
    Excerpt

    We report the case of a patient who at age 39 first developed an episode of muscle weakness and transient ketoacidosis with biopsy proven fatty infiltration of the liver. Over the next several years, myopathy ensued; biopsy revealed extensive deposition of lipid globules in type 1 muscle fibres. Further investigations established the diagnosis of systemic carnitine deficiency (SCD) with skeletal muscle, hepatic, and cardiac involvement. The patient has benefited from L-carnitine supplementation. Our case represents an unusually late onset of SCD and highlights the necessity, when appropriate, of a high index of suspicion of this rare but treatable disorder.

    Title Interaction Between Neurons in Precentral Cortical Zones Controlling Different Joints.
    Date April 1987
    Journal Brain Research
    Excerpt

    The relationship of the strength of interaction between precentral cortical neurons and their distance of separation during active reaching movements was studied in adult primates. Chronic unit recording experiments with two independent microelectrodes were performed in the left precentral forearm area of monkeys trained to execute reaching movements with the right arm in response to a visual cue. Neurons were identified by the joint actions produced by intracortical microstimulation. Cross-correlation analysis was employed to assess the strength of interaction between units. Unit pairs which exhibited the highest strength were recorded by the same electrode. For unit pairs derived from separate electrodes, the incidence and strength of interaction fell as the separation between the units was increased. Neurons identified by intracortical microstimulation as controlling the same or contiguous joints tended to interact with each other with much higher probability than did those neurons identified as controlling non-contiguous joints. When the direction of flow of information was assessed, these was a preferential flow from neurons controlling proximal joints to those controlling distal ones. These results are consistent with recent findings of tight kinematic coupling between contiguous joints and the observation of proximal-to-distal sequence of activation at the neuronal and electromyogram levels during voluntary movement.

    Title Functional Elements of the Human U1 Rna Promoter. Identification of Five Separate Regions Required for Efficient Transcription and Template Competition.
    Date March 1987
    Journal The Journal of Biological Chemistry
    Excerpt

    We have determined the structure of the human U1 snRNA promoter by microinjection of several mutant U1 templates into Xenopus laevis oocytes. These deletion templates were assayed for their ability to express mature U1 RNA and for their ability to compete for limiting transcription factors. We have mapped five separate regions, called promoter elements A, B, C, D, and E. Element A, located between positions -8 and -50, stimulates transcription 3- to 5-fold increases the accuracy of initiation; element B (between -50 and -80) fixes the site of initiation and stimulates transcription greater than 100-fold; element C (upstream of -129) increases the efficiency of element B 3- to 5-fold; element D (between -191 and -231) is an orientation-independent and partially position-independent enhancer responsible for a 100-fold stimulation of transcription; element E (between -335 and -393) increases the ability to compete with other snRNA genes 4-fold. All five promoter elements are required for effective competition with the wild-type U1 promoter suggesting that binding of transcription factor(s) to the complex is cooperative. The U1 RNA and some mRNA gene transcription complexes appear to share one or more transcription factors.

    Title Cross-correlation Analysis of Thalamic Neurons and Emg Activity in Parkinsonian Tremor.
    Date September 1986
    Journal Applied Neurophysiology
    Excerpt

    Bursting activity in cells cross-correlated with electromyographic (EMG) activity during parkinsonian tremor. Statistically significant evidence of cross-correlation was found for 49% of cells located at the lesion target for relief of tremor. Statistically significant correlation was found for 90% of cells having tremor frequency power greater than twice 'average power' at nontremor frequencies. This population of cells may be involved in the generation of parkinsonian tremor.

    Title Evoked Potentials from Passive Elbow Movements. Ii. Modification by Motor Intent.
    Date August 1986
    Journal Electroencephalography and Clinical Neurophysiology
    Excerpt

    Subjects were instructed to remain passive or to react to a forearm perturbation by opposing the imposed movement. Evoked potentials (EPs) were recorded at 8 scalp sites in both conditions. In the React condition, reflexes were observed in the EMG (mean onsets of 67 and 81 msec) and the EP was modified. Source derivation techniques revealed that the earliest cortical response (31 msec) across the central sulcus was not changed. Therefore the intention to react did not seem to affect afferent transmission to the primary sensorimotor cortex. Two periods of modulation were observed. In both, parietal and frontal potentials were modulated together, prior to the reflex components. After 70 msec, the pattern of potential gradients which occurred in the Passive case was accelerated and intensified in the React condition. The overall effect was to focus a larger zone of negativity over motor cortex at the time of triggered EMG output (109 msec). The earlier changes in cortical activity could be causally related to the appearance of the late stretch reflex. Since parietal and frontal areas were principally involved and not the motor area, it is suggested that the former exert a modulatory influence on spinal and brain-stem reflex centres.

    Title Measurements of Human Forearm Viscoelasticity.
    Date May 1986
    Journal Journal of Biomechanics
    Excerpt

    In human subjects, stiffness of the relaxed elbow was measured by three methods, using a forearm manipulandum coupled to a.d.c. torque motor. Elbow stiffness calculated from frequency response characteristics increased as the driving amplitude decreased. Step displacements of the forearm produced restoring torques linearly related to the displacement. The stiffness was very similar to that calculated from natural frequencies at amplitudes above 0.1 rad. Thirdly, elbow stiffness was estimated from brief test pulses, 120 ms in duration, by mathematically simulating the torque-displacement functions. Stiffness values in the limited linear range (under +/- 0.1 rad) were higher than in the linear range of the first two methods. A major component of elbow stiffness appears to decay within 1 s. The coefficients of viscosity determined from the simulation were, however, very similar to those calculated from the frequency response. Test pulse simulation was then used to determine joint impedance for different, actively maintained elbow angles. Joint stiffness and viscosity increased with progressive elbow flexion.

    Title The Selected Use of Ultrasound Mammography to Improve Diagnostic Accuracy in Carcinoma of the Breast.
    Date February 1986
    Journal Journal of Surgical Oncology
    Excerpt

    Our initial experience with diagnostic ultrasound mammography (UM) showed it to be of high diagnostic accuracy and improved specificity when compared with x-ray mammography (XRM) in certain categories of patients. To evaluate this modality further, we reviewed our experience with 600 consecutive patients who underwent ultrasound mammography as part of their initial evaluation for breast disease. Five categories of patients were reviewed: I: age 35 or less--129; II: DY or P-2 pattern on XRM--174; III: negative XRM but symptoms requiring additional evaluation--81; IV: high risk remaining breast in patients previously having mastectomy--48; V: refusal of repeat XRM because of pregnancy, lactation, or fear of radiation exposure--168. Fifty-five solid lesions were diagnosed, including 36 carcinomas. Seventeen of these were not diagnosed on x-ray mammography, giving an improved pick-up of carcinoma in this overall group of 2.83%. Of particular interest was that, of the 27 carcinomas that were found in the group having XRM, 8 or 29.6% were missed on that modality alone. Five of these (62.5%) were patients having a DY pattern. All patients have been followed carefully and re-examined at 3-month intervals, with no evidence of a false negative examination. Overall, we feel diagnostic ultrasound mammography is a valuable adjunct to x-ray mammography and recommend its continued use in selected groups of patients where it has a superior diagnostic accuracy over x-ray mammography alone.

    Title Use of a Highly Sensitive Assay to Analyze the Excision Repair of Dimer and Nondimer Dna Damages Induced in Human Skin Fibroblasts by 254-nm and Solar Ultraviolet Radiation.
    Date December 1985
    Journal Cancer Research
    Excerpt

    The excision repair of nondimer DNA damages induced in normal human skin fibroblasts exposed to the Mylar-filtered UV produced by a fluorescent sunlamp was investigated. This work was accomplished through the development of a modification of the bromodeoxyuridine photolysis assay that greatly increases the sensitivity of this assay. This enhancement in sensitivity was achieved through use of alkaline elution to measure the DNA strand breakage produced by the photolysis of bromodeoxyuridine incorporated into the DNA through excision repair. Using this modified bromodeoxyuridine photolysis assay, it was found that the solar UV-induced nondimer DNA damages appear to have been repaired by a short patch repair mechanism in which a small number of nucleotides (two to four) were inserted into the repaired site. This is in contrast to the long patch repair process involved in the excision of cyclobutane pyrimidine dimers in which approximately 40 nucleotides were inserted into each repaired region.

    Title Evoked Potentials from Passive Elbow Movements. I. Quantitative Spatial and Temporal Analysis.
    Date November 1985
    Journal Electroencephalography and Clinical Neurophysiology
    Excerpt

    Evoked potentials following perturbations of the forearm were recorded monopolarly at 8 scalp sites. Successive 10 msec bins of individual EPs were compared across subjects to determine intervals of consistent potential change. From this analysis it was possible to objectively sort subjects into two subpopulations with different common wave forms. Spatial vectors (potential gradient between two adjacent leads) were computed as well as Laplacian derivatives, to identify electrodes closest to source activity. Subsequently, temporal derivatives of the vectors were computed to define the timing of statistically significant response phases. To more precisely localize the largest potential gradients, component vectors (or their derivatives) in the Laplacians were resolved algebraically on a scaled representation of the scalp. Convergence of these resultant vectors from adjacent areas, identified zones of significant potential change which corresponded to known somatosensory areas. The two subpopulations had initial responses of similar topography localized to the central sulcal region. Subsequently, for one group the area of activated cortex expanded to include posterior parietal and more frontal areas. Prestimulus negative potential shifts had different distributions for the two groups and are described in relation to the poststimulus differences.

    Title Properties of Visual Cue Responses in Primate Precentral Cortex.
    Date November 1985
    Journal Brain Research
    Excerpt

    Monkeys were trained to perform a visuomotor task involving the alignment of a cursor over a vertical target line on a videomonitor by flexion or extension movements of the wrist. The forelimb area of the contralateral precentral cortex was thoroughly explored during the task. Intracortical microstimulation was employed to classify the forelimb region into wrist flexion--extension and non-wrist flexion--extension populations. Unit recording revealed an initial response to the cue for movement, viz. the appearance of the cursor and target line on the videomonitor, while visual signals not related to the task failed to evoke any response. The mean latency of these visual cue responses was approximately 150 ms. A great majority of the responses (96%) were bidirectional in character, in that they did not correlate with the directional information embedded in the visual cue, nor were they good predictors for the direction or timing of the subsequent movement. They were uniformly distributed in both the wrist and non-wrist regions of the forelimb area; the non-forelimb areas were devoid of the cue response. Further, when the variability of response to the visual cue for the wrist and non-wrist populations was compared, no significant difference was observed. These observations are consistent with an interpretation that the visually triggered cue responses provide a generalized activation over the task-related area of precentral cortex, paving the way for later and more specific activations leading to the execution of the task.

    Title Celiac Disease and Spinocerebellar Degeneration with Normal Vitamin E Status.
    Date September 1985
    Journal Neurology
    Excerpt

    We studied a 47-year-old man with spinocerebellar degeneration and malabsorption due to celiac enteropathy; the serum vitamin E level was normal. The neurologic disorder initially deteriorated despite improvement of small bowel histology on a gluten-free diet and vitamin E therapy, but later stabilized. The etiology of the neurologic disorder in adult celiac disease has not been identified and does not appear to be vitamin E deficiency.

    Title Cross Correlation Studies in Primate Motor Cortex: Synaptic Interaction and Shared Input.
    Date April 1985
    Journal The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques
    Excerpt

    Awake, unrestrained monkeys were trained to reach out with the forelimb and touch a button. Extracellular spike trains were recorded from pairs of neurons in contralateral precentral cortex with the same or separate microelectrodes. The neurons were located in the same or different functional columns as defined by intracortical microstimulation and passive sensory stimulation. Cross correlation analysis showed patterns consistent with synaptic excitation and/or inhibition between members of the cell pairs during the voluntary movement. The strength of correlation was inversely related to distance between columns, with the strongest correlations found between cells within the same column. Inhibitory correlations were virtually restricted to cell pairs within a single column. Temporal analysis showed that direct synaptic interaction and shared input patterns could be clearly distinguished in this physiologic setting. Spatial analysis indicated that shared input was concentrated among columns in the same and adjacent joint controlling zones as well as within a single column. No directional preference of shared input was present, a finding which was consistent with the observed nested organization of the forelimb area.

    Title Cross Correlation Studies in Primate Motor Cortex: Event Related Correlation.
    Date April 1985
    Journal The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques
    Excerpt

    Simultaneous extracellular unit recordings were made from each cell of 237 pairs in two awake monkeys, during a voluntary reaching movement of the forelimb. The cells were located in contralateral precentral cortex and functionally coupled to single forelimb joints, as indicated by intracortical microstimulation and passive sensory stimulation. Cross correlation analysis showed that 72 of these pairs exhibited significant event-related correlation over periods of up to 780 ms, comparable to and coincident with the forelimb movement. Spatial analysis showed that such correlation extended across contiguous portions of all four forelimb joint zones of precentral cortex, over distances up to 3.5 mm. No preferred direction of correlation was observed. The data confirm the previously described nested organization of the forelimb area of precentral cortex. Findings are discussed in terms of mechanisms by which columns of neurons in motor cortex participate in the reaching movement.

    Title Sequential Activation of Neurons in Primate Motor Cortex During Unrestrained Forelimb Movement.
    Date April 1985
    Journal Journal of Neurophysiology
    Excerpt

    We trained monkeys to perform an unrestrained, reaching movement of the arm. Electromyogram (EMG) recordings of forelimb muscles revealed sequential activation, proximal to distal, of muscle groups involved in the task. The delay in onset of EMG activity between proximal (shoulder and elbow) and distal (wrist and finger) muscles was approximately 60 ms. We identified the neurons in the forelimb area of the contralateral motor cortex as controlling particular joints by previously defined criteria involving responses to somatosensory stimulation and effects of intracortical microstimulation. Many cells discharged prior to the onset of EMG activity acting on the appropriate joint, whereas others began firing at a later phase of the movement. The population of all proximal cells altered discharge patterns approximately 60 ms earlier than the population of distal cells. A small percentage of cells showed an initial inhibitory change in discharge frequency, and this inhibition typically occurred prior to the excitatory changes seen in the majority of cells. The results are discussed in terms of the "nested-zone" model of the forelimb motor cortex. The data support one of the predictions of this model, namely that discharges of identified cells within the cortical zones are causally related to voluntary movement at appropriate forelimb joints.

    Title Human U2 and U1 Rna Genes Use Similar Transcription Signals.
    Date March 1985
    Journal The Embo Journal
    Excerpt

    We have analyzed the requirements for human U2 RNA transcription by injection of cloned U2/6 RNA genes into nuclei of Xenopus laevis oocytes. Two forms of human U2 RNAs accumulate, a major species corresponding to mature-sized U2 RNA and a minor species corresponding to a 3'-extended precursor. This RNA polymerase II transcription requires only 258 and 94 bp of 5'- and 3'-flanking region sequences, respectively. Efficient U2 RNA synthesis depends on a promoter element located between positions -258 and -198. This region contains a 12-bp direct repeat which strongly resembles a comparable upstream promoter element of the human U1 RNA genes. Sequences between -258 and -198 also confer on the U2 RNA template the ability to complete with co-injected U1 RNA templates for a snRNA gene-specific transcription factor(s). Transcription of U2 RNA is reduced off templates containing an active RNA polymerase III transcription unit, presumably because of relaxation or sequestration of the DNA. In vitro transcription of the U2 RNA gene, like that of the U1 RNA gene, is initiated upstream of the point corresponding to the 5' end of in vivo synthesized RNA.

    Title Synthesis of Human U1 Rna. Ii. Identification of Two Regions of the Promoter Essential for Transcription Initiation at Position +1.
    Date August 1984
    Journal The Journal of Biological Chemistry
    Excerpt

    We have analyzed the requirements for human U1 RNA transcription catalyzed by RNA polymerase II. In Xenopus laevis oocytes, a human U1 RNA gene with only 231 and 35 nucleotides of the 5' and 3' flanking regions, respectively (Lund, E. and Dahlberg, J. E. (1984) J. Biol. Chem. 259, 2013-2021), is able to support accumulation of human U1 RNA. We show that the point in the template corresponding to the 5' end of U1 RNA is a site of transcription initiation. That result rules out the possibility that the 5' end of U1 RNA is generated by cleavage and capping of a precursor RNA. The accumulation of correctly initiated human U1 RNA transcripts requires at least two essential upstream elements. The region between positions -231 and -203 is indispensable for transcription both in oocytes and in vitro. The other region, between positions -105 and -6, fixes the location of the 5' ends of the U1 RNA transcripts in oocytes while not altering the overall level of transcription. This latter region contains a sequence located around position -50, which we propose serves as the analog of the T-A-T-A sequence in U1 and U2 RNA genes.

    Title Long-latency Myotatic Reflexes in Man: Mechanisms, Functional Significance, and Changes in Patients with Parkinson's Disease or Hemiplegia.
    Date February 1984
    Journal Advances in Neurology
    Title Development of a Total Parenteral Nutrition Program in a Community Hospital.
    Date October 1983
    Journal The Canadian Journal of Hospital Pharmacy
    Excerpt

    The article outlines a Total Parenteral Nutrition (TPN) program now existing in a community hospital which could be introduced in other community hospitals. It also describes the role of the pharmacist as the instigator in the formation of a TPN Committee and as a contributing member of the TPN Committee.

    Title Stretch Reflex Modulation During a Cyclic Elbow Movement.
    Date July 1983
    Journal Electroencephalography and Clinical Neurophysiology
    Excerpt

    Small torque pulses were delivered to the forearm in order to test the stretch reflex of the brachialis and triceps arm muscles in 11 normal subjects performing a cyclic movement about the elbow in the horizontal plane. The flexion-extension movement was paced by a metronome and performed under various loading conditions. Reflexes for each muscle were tested either in each 50 msec segment of the 2 sec cycle period, or in a smaller number of selected phases. A late reflex, appearing at a latency of about 60 msec (measured from the onset of the torque increment), was modulated extensively during the movement cycle. The amplitude of the late reflex increased markedly at the onset of a muscle contraction. In many of the subjects reflex responsiveness began to increase as early as 200 msec prior to the onset of voluntary muscle activity. Peak reflex responses were elicited by stimuli delivered 100-150 msec prior to the peak rate of increase of dynamic load (composed of inertial, viscous and elastic forces). The increase in responsiveness was followed by a drop which was generally coincident in time with the peak rate of increase of the load opposing muscle contraction. The modulation of the late reflex is appropriately timed for reflex-generated tension to help counteract dynamic loads, intrinsic to the movement.

    Title Participation of Precentral Neurons in Somatically and Visually Triggered Movements in Primates.
    Date December 1982
    Journal Brain Research
    Excerpt

    Monkeys were trained to perform somatically and visually triggered wrist flexion-extension (F-E) movements. Extracellular unit recordings were made in the contralateral precentral forelimb area. These neurons were identified as being best related to particular single forelimb joints by their responses to passive somatosensory stimulation and to the determining effects of local intracortical microstimulation. It was found that almost 60% of single-joint related cells participated in both somatically and visually triggered movements. All wrist (F-E) neurons responded reciprocally while non-wrist (F-E) neurons had reciprocal as well as bidirectional responses to the oppositely directed visual and somatic perturbations. Somatically related responses and visually related responses were both uniformly distributed throughout the vertical layers of precentral cortex. With respect to horizontal spatial arrangements, multiple clusters of reciprocally and bidirectionally responsive neurons were intermingled. This latter finding supports the concept of a context-sensitive organization for motor control within precentral cortex.

    Title Precentral Unit Activity Correlated with Angular Components of a Compound Arm Movement.
    Date December 1982
    Journal Brain Research
    Title Transcription of a Gene for Human U1 Small Nuclear Rna.
    Date October 1982
    Journal Cell
    Excerpt

    Transcription of U1 small nuclear RNA from a 592 bp fragment of human DNA was analyzed in vivo and in vitro. When injected into Xenopus laevis oocyte nuclei, the cloned DNA is transcribed by RNA polymerase II to make human U1 snRNA. Thus the sequences of this fragment are sufficient for expression of the U1 snRNA gene. Moreover, injection of templates carrying deletions of flanking sequences demonstrates that the DNA sequences required for in vivo transcription are located at least 100 nucleotides upstream from the point corresponding to the 5' end of mature U1 snRNA. In vitro transcription in a HeLa cell extract leads to synthesis not of mature U1 snRNA, but of a larger molecule starting 183 nucleotides upstream from the site corresponding to the 5' end of mature U1 snRNA. Transcription from this upstream promoter also is catalyzed by RNA polymerase II, and is comparable in efficiency with the very strong major late promoter of adenovirus 2. We propose that U1 snRNA is synthesized in vivo as a precursor that is processed by an enzyme or enzymes missing from our extracts.

    Title Activity of Primate Precentral Neurons During Voluntary Movements Triggered by Visual Signals.
    Date June 1982
    Journal Brain Research
    Excerpt

    Awake, intact monkeys were trained to perform discrete flexion or extension movements of the hand about the wrist in response to visual signals. The object of the movement was to align a cursor, coupled to a manipulandum, on a target line. Cursor and target lines are displayed on a video monitor placed in front of the monkey. The target line was stepped to the right or left, randomly with regard to direction and timing, with each step implying an instruction for the monkey to make a voluntary movement for alignment. Single unit recording was made in the forelimb area of contralateral precentral cortex. Neurons were classified by their responses to passive sensory stimulation and the effects of local intracortical microstimulation into two populations; wrist flexion-extension (F-E) neurons, and all other forelimb neurons (non-wrist (F-E)). A significantly higher proportion of wrist (F-E) neurons as compared to non-wrist (F-E) neurons were task-related. Moreover the wrist (F-E) neurons exhibited exclusively reciprocal responses to the oppositely directed visual signals, whereas the non-wrist (F-E) neurons showed both reciprocal and bidirectional responses. No significant differences in mean latencies of responses, either in respect to the visual signals or to movement onset, were observed between the two populations of neurons. However the range of latencies in both instances was greater in the non-wrist (F-E) populations. The wrist (F-E) population showed significantly less response variability than the non-wrist (F-E) population with regard to response latencies to visual signals and movement onsets, and the degree of correlation between duration of response and reaction time.

    Title Distribution of Responses to Visual Cues for Movement in Precentral Cortex or Awake Primates.
    Date September 1981
    Journal Neuroscience Letters
    Excerpt

    Unit recordings were made from areas 4 and 6 monkeys after they were trained to align a cursor over a vertical target line on a video screen by control of a manipulandum with wrist flexion or extension movement. The appearance of the cursor and line on the screen was the visual cue for movement. Responses were observed 150 (+/- 40) msec after cue presentation. The responses were found only in the forelimb area of precentral cortex, which was most immediately involved in the control of the task, and the majority of them were uncorrelated with either the specific details of the visual cue, or with the direction of the subsequent wrist movement.

    Title Sensory-motor Processing in the Caudate Nucleus and Globus Pallidus: a Single-unit Study in Behaving Primates.
    Date May 1981
    Journal Canadian Journal of Physiology and Pharmacology
    Excerpt

    Monkeys were prepared for chronic recording of single neurons in the caudate nucleus (Cd) or globus pallidus (GP) during learned wrist flexion-extension movements triggered by visual and somatic sensory inputs. Almost two-thirds of GP cells and more than one-third of Cd cells modified their discharge during these tasks. Three categories of response types were observed. The first was movement related. The second type was event related, in which the cells responded to either the onset or offset of the sensory inputs regardless of the correcting movement direction. A third type combined elements of the first two categories and was termed complex. These cells responded to complex abstractions of the sensory-motor event. A latency analysis indicated that the majority of cells was not involved in initiating movements but may have participated in movement execution. The results of this experiment suggest that during voluntary movement the basal ganglia activity is correlated with motor outputs, sensory inputs, and perceptual abstractions of these sensory-motor events. As such the results are compatible with an influence by diverse regions of cerebral cortex on basal ganglia neurons during the movement control process.

    Title Activities of Neurons in "motor" Thalamus During Control of Limb Movement in the Primate.
    Date December 1980
    Journal Journal of Neurophysiology
    Title Recording of Simultaneous Spike Trains by Two Independent Electrodes in Awake Primates.
    Date November 1980
    Journal Physiology & Behavior
    Title Physiologic Basis for Focal Motor Seizures and the Jacksonian "march" Phenomena.
    Date November 1980
    Journal The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques
    Title The Value of Aspiration Cytology in the Evaluation of Dysplastic Breasts.
    Date August 1980
    Journal Cancer
    Excerpt

    Sixteen consecutive patients who had carcinoma of the breast and who had preoperative xeromammography were evaluated and classified according to Wolfe's classification. Five of the patients had correct preoperative evaluation by mammography, and 11 had false negatives. Eight of these were in patients who had Wolfe's classification "DY", suggesting that this is an extremely difficult group to diagnose by mammography alone. The value of aspiration cytology in this group and in all patients having breast masses is discussed. Aspiration cytology as a cellular technique for diagnosing the group with dysplastic breast is strongly recommended.

    Title Activity of Precentral Neurons During Torque-triggered Hand Movements in Awake Primates.
    Date August 1980
    Journal Canadian Journal of Physiology and Pharmacology
    Excerpt

    In monkeys performing a handle-repositioning task involving primarily wrist flexion-extension (F-E) movements after a torque perturbation was delivered to the handle, single units were recorded extracellularly in the contralateral precentral cortex. Precentral neurons were identified by passive somatosensory stimulation, and were classified into five somatotopically organized populations. Based on electromyographic recordings, it was observed that flexors and extensors about the wrist joint were specifically involved in the repositioning of the handle, while many other muscles which act at the wrist and other forelimb joints were involved in the task in a supportive role. In precentral cortex, all neuronal responses observed were temporally correlated to both the sensory stimuli and the motor responses. Visual stimuli, presented simultaneously with torque perturbations, did not affect the early portion of cortical responses to such torque perturbations. In each of the five somatotopically organized neuronal populations, task-related neurons as well as task-unrelated ones were observed. A significantly larger proportion of wrist (F-E) neurons was related to the task, as compared with the other, nonwrist (F-E) populations. The above findings were discussed in the context of a hypothesis for the function of precentral cortex during voluntary limb movement in awake primates. This hypothesis incorporates a relationship between activities of populations of precentral neurons, defined with respect to their responses to peripheral events at or about single joints, and movements about the same joint.

    Title The Role of the Basal Ganglia in Controlling a Movement Initiated by a Visually Presented Cue.
    Date August 1980
    Journal Brain Research
    Excerpt

    This study examines the effects on single neurons in caudate nucleus and globus pallidus of a visual stimulus, which is a cue to begin a tracking movement involving the forelimb on the side contralateral to the recording site. The experiments were designed to examine the relationship between activity of single neurons in these structures and movement initiation. Four monkeys were prepared for chronic recording of single neurons. The animals were trained to perform a tracking task that involved flexion and extension of the wrist at the onset of visual cue. The activities of a large proportion of neurons examined were correlated with the task, the proportion being greater in globus pallidus than in caudate nucleus. The majority of correlated neurons were activated after the onset of muscle activity and subsequent movement. It is thus unlikely that these cells were involved in movement initiation. However a role in movement execution is not excluded by the results. The fact that many cells were responsive only to certain specific conditions of the visual cue trial suggests an influence on these cells by highly processed visual information from other brain areas.

    Title Cerebellar Modulation of Reflex Gain.
    Date June 1980
    Journal Progress in Neurobiology
    Title Modifiability of the Stretch Reflex by Prior Information.
    Date January 1980
    Journal Electromyography and Clinical Neurophysiology
    Title Patterns of Early and Late Discharges in Somatotopically Identified Precentral Neurons in Awake Monkeys in Response to Somatic Inputs.
    Date December 1979
    Journal Canadian Journal of Physiology and Pharmacology
    Excerpt

    Extracellular recordings were made of single neurons in precentral cortex of awake monkeys. These neurons were somatotopically identified with respect to their responses to inputs from single joints or their somatic surround. Many of these neurons exhibited early (less than 50 ms) and late (greater than 50 ms) discharges in response to flexion or extension torques delivered about the wrist. With the monkey in a mode requiring opposition to the injected torque, all responsive neurons showed a parallel excitatory or inhibitory modification in the early and late discharges. This was true both for cells identified as wrist (flexion-extension) neurons and those identified as nonwrist (flexion-extension) neurons. These findings indicate that the reflex and voluntary components of percentral discharge invariably show a congruent functional response to a torque disturbance, for this particular instruction set.

    Title Function of Caudate Neurons During Limb Movements in Awake Primates.
    Date December 1979
    Journal Brain Research
    Excerpt

    Recordings from single neurons were made in the head of the contralateral caudate nucleus in awake primates during performance of visually and somatically guided hand movements. Populations of cells showed temporal correlation of discharge patterns with visual or somatic disturbances or both. However these discharges occurred about or after the onset of the compensating movement triggered by the disturbances. These findings indicate that the observed cells do not participate in the initiation of these compensating movements, and may instead act as part of an internal feedback loop whose function is unrelated to movement onset.

    Title Differential Effects of Reciprocal Wrist Torques on Responses of Somatotopically Identified Neurons of Precentral Cortex in Awake Primates.
    Date October 1979
    Journal Brain Research
    Excerpt

    The present study was undertaken to investigate the functional significance of previous observations that both reciprocal and bidirectional responses are found in the forelimb area of precentral cortex following oppositely directed torques delivered about a single forelimb joint. Extracellular unit recordings were made in the contralateral precentral cortex of awake monkeys. These units were classified, according to their responses to passive somatosensory stimulation and to the effects of local intracortical microstimulation (ICMS), as being functionally coupled to single joints. Both joint- and cutaneous-sensitive neurons were included. The responses of such classified neurons to oppositely directed torques were then studied. All of the joint-sensitive wrist (flexion-extension) units responded reciprocally to the oppositely directed torques. In contrast reciprocally and bidirectionally responsive neurons were found in the cutaneous-sensitive wrist population and in both the joint- and cutaneous-sensitive non-wrist (F-E) populations. These results are discussed in terms of the expected receptor actions of the applied torques, and are consistent with other evidence that a correlation exists between activities of precentral neurons which respond to sensory events at or about a single forelimb joint, and voluntary movement about the same joint.

    Title Control of Stiffness by the Medium Latency Electromyographic Response to Limb Perturbation.
    Date August 1979
    Journal Canadian Journal of Physiology and Pharmacology
    Excerpt

    It is hypothesized that the medium latency electromyographic (EMG) response (ML) to limb perturbation functions to preset limb stiffness to a constant initial level. Three predictions are derived from this hypothesis: Firstly, in the presence of an instruction calling for opposition to limb perturbation, a control signal, ML, will be observed and will lead to the establishment of a constant level of limb stiffness. Secondly, in the absence of an instruction to oppose, no control signal will be observed and correspondingly a constant stiffness will not be generated. Thirdly, the latency of onset of stiffness control will covary with the latency of onset of ML. These predictions were tested in experiments involving perturbation of the human forearm about the elbow joint, with surface EMG measurements and computation of the limb stiffness function. The results are in accord with these predictions, and support the hypothesis that ML functions in the feedforward control of limb stiffness.

    Title An Intracortical Microstimulation Study of Output Organization in Precentral Cortex of Awake Primates.
    Date February 1979
    Journal Journal De Physiologie
    Excerpt

    We investigated the output organization of the forelimb control area in primate precentral cortex by using low-current (less than 30 microamperemeter) intracortical microstimulation (ICMS). Movement about a joint was selected as the index of response. Penetrations perpendicular to the cortical surface and deep into the rostral bank of the central sulcus were made in two awake unanesthetized monkeys (Macaca arctoides). Cortical areas were designated by the joint about which movements occurred. 1. ICMS loci which produced movements about finger joints were found to tightly cluster in a central zone, and were surrounded by loci controlling movement about the wrist. This wrist zone was in turn approximately encircled by an elbow zone, which itself was enclosed by a shoulder zone. 2. Appreciable overlap between these zones controlling movements about contiguous joints was observed. 3. The observations indicate a nested-ring organization of the forelimb output zones of precentral cortex, such that a cortical zone controlling movement of a more distal joint is partly encircled by the zone controlling a more proximal joint.

    Title The Electromyographic Response to Sudden Stretches of Limb Muscles in Normal Human Subjects.
    Date January 1979
    Journal Canadian Journal of Physiology and Pharmacology
    Excerpt

    The electromyographic (EMG) activity following a sudden stretch applied to wrist flexor or extensor muscles was investigated using a method which enabled the individual records and cumulative results of 30 trials to be observed simultaneously. The results showed that in each case the spinal reflex EMG burst was followed by one or two additional reflex bursts. The second of these latter bursts, when present, occurred in one of two distinct latency ranges. Thus, three distinct latency ranges were observed for reflex bursts following the spinal reflex burst. A possible explanation for these results is that there are three distinct long-loop reflexes, one or two of which may be active following a muscle stretch. The present results do not distinguish whether any or all of these long-loop reflexes are segmental or supraspinal in origin.

    Title Spatial Organization of Precentral Cortex in Awake Primates. I. Somatosensory Inputs.
    Date December 1978
    Journal Journal of Neurophysiology
    Title Spatial Organization of Precentral Cortex in Awake Primates. Ii. Motor Outputs.
    Date December 1978
    Journal Journal of Neurophysiology
    Title Spatial Organization of Precentral Cortex in Awake Primates. Iii. Input-output Coupling.
    Date December 1978
    Journal Journal of Neurophysiology
    Title Withdrawal from Long-term High-dose Desipramine Therapy. Clinical and Biological Changes.
    Date November 1978
    Journal Archives of General Psychiatry
    Excerpt

    Investigation was undertaken on a patient whose long-term intake of desipramine hydrochloride was amongst the highest reported. Desipramine treatment instituted at a daily dosage of 75 mg for depressive equivalents of head, chest, and abdominal pain was increased to 1,000 mg daily over a 12-year interval with minimal side effects. Plasma desipramine level dropped immediately on withdrawal, and urinary metabolite values dropped over the subsequent five days. The electrocardiographic abnormalities of first-degree atrioventricular block and incomplete left bundle branch block rapidly disappeared on cessation of medication. Electroencephalographic changes with symmetrical generalized irregular 5- to 7-cps theta activity and 18- to 28-cps beta activity also improved. Longitudinal polygraphic sleep studies showed prolonged rapid eye movement rebound and increased delta sleep coincident with withdrawal. It took ten days after cessation of desipramine for urinary 3-methoxy-4-hydroxyphenylglycol concentration to increase substantially. Although catecholamines are involved in growth hormone (GH) and cortisol regulation, no abnormalities were found in GH or cortisol levels.

    Title The Influence of a Visual Cue on Muscle Stretch Reflexes.
    Date June 1978
    Journal Canadian Journal of Physiology and Pharmacology
    Excerpt

    Evidence has recently been presented indicating that muscle stretch reflexes have a large supraspinal component. The finding introduces the possibility that stretch reflex parameters may be modifiable by stimuli involving other modalities besides stretch. In this investigation, the effects of a visual cue on the reflex portions of the EMG activity following a sudden muscle stretch were examined. The results, obtained from the flexor carpi radialis muscles of six normal awake subjects, failed to show any significant change in the EMG parameters as a result of visual cues occurring at the instant of onset of muscle stretch. This was interpreted as indicating that visual inputs do not reach the areas of brain involved in the supraspinal reflex in sufficient time to modify the reflex.

    Title Genesis of the Round Window Rupture Syndrome; Some Experimental Observations.
    Date April 1978
    Journal The Laryngoscope
    Excerpt

    Clinical and experimental evidence has revealed that rupture of the round window membrane, by itself, is not a major cause of sensorineural hearing loss. Eighteen guinea pigs underwent removal of the round window. The status of cochlear function was determined by recording the cochlear microphonic. An average loss of only about 6 db was observed after surgery. It is felt that there must commonly be more cochlear damage concurrent with window rupture to explain the significant and often relatively immediate hearing losses seen in clinical practice. The site(s) of this primary trauma has not yet been discovered, but it would seen reasonable in the light of recent reports that the perilymphatic vessels, the vas spirale, the stria vascularis and/or the intergrity of the cochlear duct might be involved in the genesis of this hearing loss. We propose that the term "round window rupture syndrome" be used as a more accurate description of this entity. The round window damage provides evidence of more devastating trauma within the cochlea. Thus, the clinician, being alerted, should not stop his therapeutic efforts with surgical closure of the RW. Better prognosis for the patient, as well as leading into new avenues for the investigation of cochlear function, would be the result.

    Title Simple Probe for Localized Cryogenic Blockade in the Brain.
    Date April 1978
    Journal Physiology & Behavior
    Excerpt

    The construction of a simple probe utilizing an air-space thermal insulation and circulating coolant for localized cooling of brain tissue is described. Results of isotherm studies in the cerebellum and electrophysiological observations in the motor cortex are presented indicating the effectiveness of localized cooling by the probe.

    Title Topographic Organization of Afferent Inputs in Monkey Precentral Cortex.
    Date February 1978
    Journal Brain Research
    Title Urological Problems in Aged Patients.
    Date June 1977
    Journal Australian Family Physician
    Excerpt

    The major urological problems encountered in geriatric patients are bladder neck obstruction, due to hyperplasia or carcinoma of the prostate in men, and urinary infection and chronic urethro-trigonitis (the urethral syndrome) in women. Senile incontinence is common to both sexes.

    Title Integrative Versus Delay Line Characteristics of Cerebellar Cortex.
    Date August 1976
    Journal The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques
    Excerpt

    In order to determine which of two general models ("tapped delay line" or "integrator") provides a more accurate desciption of mammalian Purkinje cell (P-cell) activation by natural stimulation, the spatial and temporal characteristics of a population of neurons in cerebellar cortex responsive to small controlled stretches of forelimb muscles were examined in awake, locally anesthetized cats. Stretch of a single wrist muscle excited P-cells over a distance of about 1 mm in the long axis of a folium, a span which is at most half the length of parallel fibers. Both granule cells and molecular layer interneurons were excited over a wider zone than P-cells. Furthermore, P-cells across a response zone all fired on the average at the same time, as determined by computing peristimulus cross-interval histograms from pairs of simultaneously recorded neurons. Consistent delays could only be demonstrated in the minimal response latencies as measured from peristimulus time histograms. These delays, however, were longer than could be ascribed to parallel fiber conduction velocity. No evidence, therefore, was found in cat cerebellum to support the "tapped delay line" model, which postulates the successive activation of P-cells as an excitatory volley travels along a parallel fiber beam. Instead, an integrative mode of operation seems to predominate: a relatively wide substratum of activated granule cells simultaneously activates a narrower focus of P-cells centrally situated with respect to the granule cell population. The role of inhibitory interneurons in promoting the "integrator" model is discussed.

    Title Effect of Succinylcholine on Responses of Neurons in the Motor Cortex to Natural Activation of Muscle Spindle Primary Endings.
    Date February 1976
    Journal Canadian Journal of Physiology and Pharmacology
    Excerpt

    In locally anesthetized cats, the effects of intravenous administration of succinylcholine (SCh) in sub-paralytic dosages on the responses of single neurons in motor cortex to small dynamic muscle stretches were studied. A large transient enhancement of these cortical responses with a time course corresponding to the peripheral action of SCh on muscle spindles was observed. This finding is discussed in terms of the hypothesis that muscle spindle primary endings may activate projections to motor cortex.

    Title Distributed Feedback Systems for Muscle Control.
    Date January 1976
    Journal Brain Research
    Title Physiological Basis of Cerebellar Dysmetria.
    Date December 1975
    Journal The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques
    Excerpt

    A primary control system for the arm position is formulated. The hypothesis that the cerebellum is a part of the system controller is checked by studying the nerve cells responses in the cerebellum, and motor cortex, to natural activation of muscular receptors. The results show that the cerebellum receives feedback information related to the speed of these receptors. The discussion concentrates on how the interruption of this feedback may result in excessive oscillations to instability. These observations are the base for evaluating how the cerebral lesions produce dismeasurements.

    Title Signal Conditioner for Neurophysiology.
    Date December 1975
    Journal Medical & Biological Engineering
    Title Afferent-efferent Linkages in Motor Cortex for Single Forelimb Muscles.
    Date November 1975
    Journal Journal of Neurophysiology
    Excerpt

    1. In locally anesthetized cats, extracellular recordings were made from single neurons in the lateral cruciate gyrus of cerebral cortex. These neurons responded to natural activation of stretch receptors in single, contralateral, forelimb wrist muscles, typically with phasic excitation. Low-velocity stretches, which activate primary endings of muscle spindles, excited one set of neurons at a mean latency of 11 ms; high-velocity stretches, which principally activate Golgi tendon organs and/or secondary spindle endings, excited a second set at 18 ms. The cortical neurons showing threshold responses to low-velocity stretches were found exclusively within restricted columns, 0.5-2.0 mm in diameter, which were spatially separate for each muscle. Neurons exhibiting threshold responses to high-velocity stretches were present in high density within the same columns and were also distributed, although more sparsely, outside the columns. 2. These afferent columns were located in cytoarchitectonic area 4gamma, and were shown by intracortical microstimulation to coincide with the efferent columns for contraction of the same muscle from which in input rose. Discrete afferent columns were also found for single muscles in the peridimple region of sensory cortex (area 3a), spatially separate from the columns in motor cortex. The excitation of the columns in motor cortex by these inputs from muscle was independent of that in sensory cortex. 3. The role of the cerebellum in controlling these feedback systems to motor cortex was investigated by selective cooling of interpositus and dentate nucleus, respectively. Cooling of interpositus markedly reduced transmission in the high-threshold system; cooling of dentate had a similar effect on the low-threshold system. 4. The latency, threshold, and cooling data indicated that the low-threshold system to motor cortex utilizes extracerebellar pathways including medial lemniscus and is facilitated by dentate nucleus. The high-threshold system involves a transcerebellar pathway including interpositus nucleus. Both systems transmit velocity-related information, with each showing different and complementary sensitivity and dynamic range. 5. The results are discussed with reference to the cortical load-compensation mechanism postulated by Phillips (37-38).

    Title Responses of Interpositus Neurons to Passive Muscle Stretch.
    Date March 1975
    Journal Journal of Neurophysiology
    Title Extracellular Current Density Analysis of Responses in Cerebellar Cortex to Mossy Fiber Activation.
    Date December 1974
    Journal Journal of Neurophysiology
    Title Evaluation of Neuronal Spike Trains in Neurophysiological Experiments.
    Date December 1974
    Journal Physiology & Behavior
    Title Projection of Primary Muscle Spindle Afferents to Motorsensory Cortex.
    Date August 1974
    Journal Canadian Journal of Physiology and Pharmacology
    Title Electrical Conductivity in Cat Cerebellar Cortex.
    Date July 1974
    Journal Experimental Neurology
    Title Extracellular Current Density Analysis of Responses in Cerebellar Cortex to Climbing Fiber Activation.
    Date April 1974
    Journal Journal of Neurophysiology
    Title A Basis for Extracellular Current Density Analysis in Cerebellar Cortex.
    Date April 1974
    Journal Journal of Neurophysiology
    Title Activation of Anterior Interpositus Neurons by Forelimb Muscle Stretch.
    Date September 1973
    Journal Brain Research
    Title Differences Between Cerebellar Mossy and Climbing Fibre Responses to Natural Stimulation of Forelimb Muscle Proprioceptors.
    Date August 1973
    Journal Brain Research
    Title Responses of Cerebellar Cortical Neurons to Dynamic Proprioceptive Inputs from Forelimb Muscles.
    Date August 1973
    Journal Journal of Neurophysiology
    Title Response of Frog Muscle Spindle System to Whole-muscle Input Parameters.
    Date June 1973
    Journal The American Journal of Physiology
    Title Muscle-pulling System for Studies of Neural Function.
    Date May 1973
    Journal Medical & Biological Engineering
    Title Pulse-height Discriminator for a Neurophysiology-computer Interface.
    Date May 1973
    Journal Medical & Biological Engineering
    Title Computer Interface for Neurophysiology.
    Date May 1973
    Journal Medical & Biological Engineering
    Title Activation of Mossy Fiber Inputs to Cerebellar Cortex by Natural Stimulation.
    Date October 1972
    Journal Brain Research
    Title Transport of S-adenosylmethionine in Saccharomyces Cerevisiae.
    Date April 1972
    Journal Journal of Bacteriology
    Excerpt

    The properties of a specific system for the transport of S-adenosylmethionine in yeast are described. The process was pH-, temperature-, and energy-dependent, and showed saturation kinetics. The K(m) for the system was 3.3 x 10(-6)m. Of the S-adenosylmethionine moieties tested, only S-adenosylhomocysteine competitively inhibited the uptake of the adenosylsulfonium compound. Adenine, adenosine, methionine, homocysteine, and the sulfonium compound S-methylmethionine were without effect. The analogue S-adenosylethionine showed competitive inhibition. Under conditions of inhibition of protein synthesis by cycloheximide or methionine starvation, permease activity was stable. The mutant sam-p3 apparently was able to transport S-adenosylmethionine only by diffusion. Uptake by diploids containing this mutation was directly proportional to the gene dose.

    Title Frog Muscle Spindle Impulse Responses to Whole Muscle Inputs.
    Date March 1972
    Journal Brain Research
    Title Afferent Volleys in Limb Nerves Influencing Impulse Discharges in Cerebellar Cortex. I. In Mossy Fibers and Granule Cells.
    Date November 1971
    Journal Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
    Title Afferent Volleys in Limb Nerves Influencing Impulse Discharges in Cerebellar Cortex. Ii. In Purkynè Cells.
    Date November 1971
    Journal Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
    Title Investigations on Integration of Mossy Fiber Inputs to Purkynè Cells in the Anterior Lobe.
    Date November 1971
    Journal Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
    Title Afferent Volleys in Limb Nerves Influencing Impulse Discharges in Cerebellar Cortex. I. In Mossy Fibers and Granule Cells.
    Date November 1971
    Journal Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
    Title Investigations on Integration of Mossy Fiber Inputs to Purkynĕ Cells in the Anterior Lobe.
    Date November 1971
    Journal Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
    Title Afferent Volleys in Limb Nerves Influencing Impulse Discharges in Cerebellar Cortex. Ii. In Purkynĕ Cells.
    Date November 1971
    Journal Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
    Title A Superposition Model of the Spontaneous Activity of Cerebellar Purkinje Cells.
    Date July 1971
    Journal Biophysical Journal
    Excerpt

    Based on physiological evidence for multiple firing zones in the dendritic arborizations of cerebellar Purkinje cells, a superposition model is proposed for spike triggering in these cells. Spike trains from 10 Purkinje cells were analyzed in terms of independence of interspike intervals and the properties of their variance-time curves. The results of this analysis were found consistent with the hypothesis that the spike train of a cerebellar Purkinje cell is the pooled output of a relatively large number of independent component processes. Simplifying assumptions as to the statistical nature of these processes lead to a very rough estimate of the number of firing zones.

    Title Cerebellar Purkinje Cell Responses to Afferent Inputs. I. Climbing Fiber Activation.
    Date April 1971
    Journal Brain Research
    Title Cerebellar Purkinje Cell Responses of Afferent Inputs. Ii. Mossy Fiber Activation.
    Date April 1971
    Journal Brain Research
    Title Responses of Cerebellar Purkinje Cells to Mossy Fiber Activation.
    Date October 1970
    Journal Brain Research
    Title The Inhibitory Effect of Climbing Fiber Activation on Cerebellar Purkinje Cells.
    Date June 1970
    Journal Brain Research
    Title Spontaneous Firing of Cerebellar Purkinje Cells in Decerebrate and Barbiturate Anesthetized Cats.
    Date March 1970
    Journal Brain Research
    Title Axonal Branching in the Climbing Fiber Pathway to the Cerebellum.
    Date October 1969
    Journal Brain Research
    Title Electrophysiological Studies of Amygdalo-hypothalamic Connections.
    Date August 1969
    Journal Annals of the New York Academy of Sciences
    Title Firing Patterns of Purkinje Cells in Response to Volleys from Limb Nerves.
    Date July 1969
    Journal Brain Research
    Title Mechanisms of Inhibition in the Ventromedial Nucleus of the Hypothalamus.
    Date April 1969
    Journal Journal of Neurophysiology
    Title Contrasting Effects of Two Identified Amygdaloid Efferent Pathways on Single Hypothalamic Neurons.
    Date December 1968
    Journal Journal of Neurophysiology
    Title Inhibitory Interneurons in the Ventromedial Nucleus of the Hypothalamus.
    Date November 1968
    Journal Brain Research
    Title Responses of Hypothalamic Neurons to Repetitive Amygdaloid Stimulation.
    Date July 1968
    Journal Brain Research
    Title Convergence of Impulses Upon Single Hypothalamic Neurons.
    Date July 1968
    Journal Brain Research
    Title Topographical Differences in the Responses of Single Hypothalamic Neurons to Limbic Stimulation.
    Date July 1968
    Journal The American Journal of Physiology
    Title Evidence for Dual Amygdalo-hypothalamic Projection System.
    Date April 1968
    Journal Electroencephalography and Clinical Neurophysiology
    Title A Comparison of Electroencephalography and Brain Scan in Supratentorial Tumors.
    Date March 1967
    Journal The New England Journal of Medicine
    Title Locus and Orientation of the Perceiver (ego) and the Rotation of Visual Images.
    Date June 1966
    Journal Journal of Personality and Social Psychology
    Title A Theoretical Analysis of the Pro-drug Delivery System for Treating Antibiotic-resistant Bacteria.
    Date
    Journal Ieee/acm Transactions on Computational Biology and Bioinformatics / Ieee, Acm
    Excerpt

    Simulations were carried out to analyze a promising new anti-microbial treatment strategy for targeting antibiotic-resistant bacteria called the beta-lactamase-dependent pro-drug delivery system. In this system, the anti-bacterial drugs are delivered as inactive precursors that only become activated after contact with an enzyme characteristic of many species of antibiotic-resistant bacteria (beta-lactamase enzyme). The addition of an activation step contributes an extra layer of complexity to the system that can lead to unexpected emergent behaviour. In order to optimize for treatment success and minimize the risk of resistance development there must be a clear understanding of the system dynamics taking place and how they impact on the overall response. It makes sense to use a systems biology approach to analyse this method because it can facilitate a better understanding of the complex emergent dynamics arising from diverse interactions in populations. This article contains an initial theoretical examination of the dynamics of this system of activation and an assessment of its therapeutic potential from a theoretical standpoint using an agent-based modelling approach. It also contains a case study comparison with real-world results from an experimental study carried out on two pro-drug candidate compounds in the literature.

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