Browse Health
Primary Care Doctor, Family Practitioner
6 years of experience
Accepting new patients

Education ?

Medical School
University of Guadalajara, Mexico (2004)

Awards & Distinctions ?

Awards  
Patients' Choice Award (2012 - 2013)
Compassionate Doctor Recognition (2012)
Associations
American Board of Family Medicine

Affiliations ?

Dr. Allen is affiliated with 4 hospitals.

Hospital Affilations

Score

Rankings

  • Banner Heart Hospital
    6750 E Baywood Ave, Mesa, AZ 85206
    • Currently 4 of 4 crosses
    Top 25%
  • Banner Baywood Medical Center
    6644 E Baywood Ave, Mesa, AZ 85206
    • Currently 4 of 4 crosses
    Top 25%
  • Banner Gateway Medical Center
    1900 N Higley Rd, Gilbert, AZ 85234
  • Mercy Medical Center North Iowa
  • Publications & Research

    Dr. Allen has contributed to 87 publications.
    Title The Architecture of Copa from Archeaoglobus Fulgidus Studied by Cryo-electron Microscopy and Computational Docking.
    Date December 2011
    Journal Structure (london, England : 1993)
    Excerpt

    CopA uses ATP to pump Cu(+) across cell membranes. X-ray crystallography has defined atomic structures of several related P-type ATPases. We have determined a structure of CopA at 10 Å resolution by cryo-electron microscopy of a new crystal form and used computational molecular docking to study the interactions between the N-terminal metal-binding domain (NMBD) and other elements of the molecule. We found that the shorter-chain lipids used to produce these crystals are associated with movements of the cytoplasmic domains, with a novel dimer interface and with disordering of the NMBD, thus offering evidence for the transience of its interaction with the other cytoplasmic domains. Docking identified a binding site that matched the location of the NMBD in our previous structure by cryo-electron microscopy, allowing a more detailed view of its binding configuration and further support for its role in autoinhibition.

    Title Safety and Cost Effectiveness of Early Discharge Following Microscopic Trans-sphenoidal Resection of Pituitary Lesions.
    Date July 2011
    Journal Surgical Neurology International
    Excerpt

    Inpatient hospitalization following trans-sphenoidal resection of a pituitary neoplasm has traditionally involved a hospital stay of 2 days or more. It has been the policy of the senior pituitary neurosurgeon (GSA) since February 2008 to allow discharge home on postoperative day (POD) 1 if thirst mechanism is intact and the patient is tolerating oral hydration. The goal of this study was to evaluate the safety and cost-effectiveness of this practice.

    Title Disorders of Water Metabolism Following Transsphenoidal Pituitary Surgery: a Single Institution's Experience.
    Date September 2008
    Journal Pituitary
    Excerpt

    Disorders of water metabolism are a common complication of pituitary surgery. The primary purpose of this study was to determine the incidence and duration of post-surgical diabetes insipidus (DI) at our institution. Secondary objectives included characterizing the incidence of post-operative hyponatremia as well as delineating factors associated with the onset of these complications. Records of 319 patients who underwent transsphenoidal pituitary surgery at the authors' institution between 1998 and 2005 were reviewed for the presence of disorders of water metabolism using pre-specified criteria. DI was diagnosed in 59 (18.5%) of our patients at a mean time of 13.6 h following surgery. DI resolved in nearly half of our patients within one week. Approximately 80% of our patients enjoyed resolution of DI at a mean time of 2.9 months following surgery. Duration of DI was not significantly influenced by tumor size or location. Additionally, 28 (8.8%) of our patients exhibited a period of hyponatremia at a mean time of 4 days following surgery. One quarter of these patients carried a diagnosis of Cushing's disease. We herein report an incidence of DI as well as hyponatremia within our post-operative population comparable to that reported by other high-volume pituitary centers. Over half of our patients still exhibited DI at the time of discharge, therefore, patient education regarding the treatment of DI, signs of its resolution, and symptoms consistent with the onset of hyponatremia should be an integral part of every hospitalization.

    Title Structural Insights on the Translation Initiation Complex: Ghosts of a Universal Initiation Complex.
    Date June 2007
    Journal Molecular Microbiology
    Excerpt

    All living organisms utilize ribosomes to translate messenger RNA into proteins. Initiation of translation, the process of bringing together mRNA, initiator transfer RNA, and the ribosome, is therefore of critical importance to all living things. Two protein factors, IF1 (a/eIF1A) and IF2 (a/eIF5B), are conserved among all three kingdoms of life and have been called universal initiation factors (Roll-Mecak et al., 2001). Recent X-ray, NMR and cryo-EM structures of the universal factors, alone and in complex with eubacterial ribosomes, point to the structural homology among the initiation factors and initiation complexes. Taken together with genomic and functional evidence, the structural studies allow us to predict some features of eukaryotic and archaeal initiation complexes. Although initiation of translation in eukaryotes and archaea requires more initiation factors than in eubacteria we propose the existence of a common denominator initiation complex with structural and functional homology across all kingdoms of life.

    Title Mid-term Results After Thoracoscopic Transmyocardial Laser Revascularization.
    Date September 2006
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: Transmyocardial revascularization is a surgical therapy for the relief of severe angina in patients who are not suitable candidates for coronary artery bypass graft surgery or percutaneous coronary interventions. Historically, surgical techniques employed a left thoracotomy with or without thoracoscopic assist for visualization. This study evaluated the feasibility and midterm outcomes after transmyocardial laser revascularization performed using a completely thoracoscopic, closed chest approach. METHODS: Patients (9 men [90%] and 1 woman [10%]) at a mean age of 66 +/- 10 years who were ineligible for coronary artery bypass graft surgery or percutaneous coronary intervention underwent sole therapy transmyocardial laser revascularization using a completely thoracoscopic surgical approach using a holmium:yttrium-aluminum-garnet laser system. Preoperatively, patients had a mean ejection fraction of 0.51 +/- 0.09 and a mean angina class of 3.7 +/- 0.5. RESULTS: A mean of 30 +/- 2.4 channels were created during mean laser and operative procedure times of 14 +/- 2.9 and 133 +/- 32 minutes, respectively. Patients were extubated at a mean of 7.6 +/- 12 hours and were discharged from the hospital at a mean of 5.4 +/- 3.4 days. There were no hospital deaths or major complications. At a mean of 8.4 +/- 5.5 months postoperatively, all patients survived and significant clinical improvement with a mean angina class of 1.3 +/- 0.5 (p < 0.001). CONCLUSIONS: A completely thoracoscopic surgical approach is feasible for sole therapy transmyocardial revascularization that affords improved visualization over a limited thoracotomy approach. Limited complications and significant clinical improvement after the procedure were observed. With minimal port manipulation, there is an opportunity for decreased postoperative pain; however, larger studies are warranted to verify this hypothesis.

    Title Visualization of a Group Ii Intron in the 23s Rrna of a Stable Ribosome.
    Date August 2006
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Thousands of introns have been localized to rRNA genes throughout the three domains of life. The consequences of the presence of either a spliced or an unspliced intron in a rRNA for ribosome assembly and packaging are largely unknown. To help address these questions, and to begin an intron imaging study, we selected a member of the self-splicing group II intron family, which is hypothesized to be the progenitor not only of spliceosomal introns but also of non-LTR retrotransposons. We cloned the self-splicing group II Ll.LtrB intron from Lactococcus lactis into L. lactis 23S rRNA. The 2,492-nt Ll.LtrB intron comprises a catalytic core and an ORF, which encodes a protein, LtrA. LtrA forms a ribonucleoprotein (RNP) complex with the intron RNA to mediate splicing and mobility. The chimeric 23S-intron RNA was shown to be splicing proficient in its native host in the presence of LtrA. Furthermore, a low-resolution cryo-EM reconstruction of the L. lactis ribosome fused to the intron-LtrA RNP of a splicing-defective Ll.LtrB intron was obtained. The image revealed the intron as a large, well defined structure. The activity and structural integrity of the intron indicate not only that it can coexist with the ribosome but also that its presence permits the assembly of a stable ribosome. Additionally, we view our results as a proof of principle that ribosome chimeras may be generally useful for studying a wide variety of structured RNAs and RNP complexes that are not amenable to NMR, crystallographic, or single-particle cryo-EM methodologies.

    Title The Cryo-em Structure of a Translation Initiation Complex from Escherichia Coli.
    Date July 2005
    Journal Cell
    Excerpt

    The 70S ribosome and its complement of factors required for initiation of translation in E. coli were purified separately and reassembled in vitro with GDPNP, producing a stable initiation complex (IC) stalled after 70S assembly. We have obtained a cryo-EM reconstruction of the IC showing IF2*GDPNP at the intersubunit cleft of the 70S ribosome. IF2*GDPNP contacts the 30S and 50S subunits as well as fMet-tRNA(fMet). IF2 here adopts a conformation radically different from that seen in the recent crystal structure of IF2. The C-terminal domain of IF2 binds to the single-stranded portion of fMet-tRNA(fMet), thereby forcing the tRNA into a novel orientation at the P site. The GTP binding domain of IF2 binds to the GTPase-associated center of the 50S subunit in a manner similar to EF-G and EF-Tu. Additionally, we present evidence for the localization of IF1, IF3, one C-terminal domain of L7/L12, and the N-terminal domain of IF2 in the initiation complex.

    Title The Efficacy of Linear Accelerator Radiosurgery in the Management of Patients with Cushing's Disease.
    Date April 2005
    Journal Stereotactic and Functional Neurosurgery
    Excerpt

    We identified 35 patients who had undergone stereotactic radiosurgery (SRS) for their biochemically proven Cushing's disease in order to assess the efficacy of SRS with regard to control of hypercortisolism, improvement of clinical features and prevention of tumor progression, and subsequent incidence of hypopituitarism. Seventeen (49%) patients achieved control of their cortisol levels following SRS; the mean time to normalization was 7.5 months (range: 1-33). Four (19%) patients experienced recurrent hypercortisolism at a mean time of 35.5 months following therapy (range: 17-64). Control of tumor progression was achieved in 91% patients. Fourteen (40%) patients demonstrated a new pituitary deficiency following SRS. Our results suggest that cortisol levels are normalized more efficiently and with a lower recurrence rate with SRS than with conventional fractionated external beam radiotherapy (EBT). We have confirmed the near 100% tumor control rate reported with SRS. The percentage of patients developing pituitary insufficiency following SRS is less than that of patients having undergone EBT; however, deficits occurred up to 10 years posttreatment. We advocate the use of SRS as the primary therapeutic modality in those patients who are poor surgical candidates, or as the adjunct treatment to microsurgery in eliminating residual tumor cells or disease that is not easily amenable to resection.

    Title Structural Basis for Allosteric Control of the Transcription Regulator Ccpa by the Phosphoprotein Hpr-ser46-p.
    Date November 2004
    Journal Cell
    Excerpt

    Carbon catabolite repression (CCR) is one of the most fundamental environmental-sensing mechanisms in bacteria and imparts competitive advantage by establishing priorities in carbon metabolism. In gram-positive bacteria, the master transcription regulator of CCR is CcpA. CcpA is a LacI-GalR family member that employs, as an allosteric corepressor, the phosphoprotein HPr-Ser46-P, which is formed in glucose-replete conditions. Here we report structures of the Bacillus megaterium apoCcpA and a CcpA-(HPr-Ser46-P)-DNA complex. These structures reveal that HPr-Ser46-P mediates a novel two-component allosteric DNA binding activation mechanism that involves both rotation of the CcpA subdomains and relocation of pivot-point residue Thr61, which leads to juxtaposition of the DNA binding regions permitting "hinge" helix formation in the presence of cognate DNA. The structure of the CcpA-(HPr-Ser46-P)-cre complex also reveals the elegant mechanism by which CcpA family-specific interactions with HPr-Ser46-P residues Ser46-P and His15 partition the high-energy CCR and low-energy PTS pathways, the latter requiring HPr-His15-P.

    Title Crystal Structure of Hpr Kinase/phosphatase from Mycoplasma Pneumoniae.
    Date April 2003
    Journal Journal of Molecular Biology
    Excerpt

    HPr kinase/phosphatase (HPrK/P) modifies serine 46 of histidine-containing protein (HPr), the phosphorylation state of which is the control point of carbon catabolite repression in low G+C Gram-positive bacteria. To understand the structural mechanism by which HPrK/P carries out its dual, competing activities we determined the structure of full length HPrK/P from Mycoplasma pneumoniae (PD8 ID, 1KNX) to 2.5A resolution. The enzyme forms a homo-hexamer with each subunit containing two domains connected by a short loop. The C-terminal domain contains the well-described P-loop (Walker A box) ATP binding motif and takes a fold similar to phosphoenolpyruvate carboxykinase (PEPCK) from Escherichia coli as recently described in other HPrK/P structures. As expected, the C-terminal domain is very similar to the C-terminal fragment of Lactobacillus casei HPrK/P and the C-terminal domain of Staphylococcus xylosus HPrK/P; the N-terminal domain is very similar to the N-terminal domain of S.xylosus HPrK/P. Unexpectedly, the N-terminal domain resembles UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:meso-diaminopimelate ligase (MurE), yet the function of this domain is unclear. We discuss these observations as well as the structural significance of mutations in the P-loop and HPrK/P family sequence motif.

    Title Immunohistochemical Localization of Carboxypeptidases D, E, and Z in Pituitary Adenomas and Normal Human Pituitary.
    Date January 2003
    Journal The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society
    Excerpt

    Carboxypeptidases may play important role(s) in prohormone processing in normal and neoplastic adenohypophyseal cells of the pituitary. We have recently demonstrated carboxypeptidase E (CPE) and carboxypeptidase Z (CPZ) in the majority of adenohypophyseal cells with carboxypeptidase D (CPD) immunoreactivity largely confined to adrenocorticotrophs. This study evaluated the expression patterns of CPE, CPD, and CPZ immunoreactivity in 48 pituitary adenomas. Our immunohistochemistry demonstrated extensive intracytoplasmic immunoreactivity for CPE, CPD, and CPZ in adrenocorticotrophic hormone (ACTH)-producing adrenocorticotroph cells, prolactin-producing lactotroph cells, and growth hormone (GH)-producing somatotroph cell adenomas, all of which require carboxypeptide processing of prohormones to produce active endocrine hormones. In contrast to the restricted expression in the normal adenohypophysis, CPD appeared to be widespread in the majority of adenomas, suggesting that CPD levels are increased in adenomas. In luteinizing hormone/follicle-stimulating hormone (LH/FSH)-producing gonadotroph adenomas, which do not require carboxypeptidases to produce gonadotropins, only CPZ immunostaining was demonstrated. In null-cell adenomas, CPE immunoreactivity was detected in the majority of tumors, but CPD and CPZ were identified only in a minority of cases. CPE in these cells may process other peptides critical for pituitary cell function, such as chromogranin A or B. These findings suggest that CPs participate in the functioning of pituitary adenomas.

    Title Lovastatin is a Potent Inhibitor of Meningioma Cell Proliferation: Evidence for Inhibition of a Mitogen Associated Protein Kinase.
    Date October 2002
    Journal Journal of Neuro-oncology
    Excerpt

    Lovastatin inhibits 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase the rate limiting enzyme for synthesis of mevalonic acid, a precursor for cholesterol, farnesyl and geranylgeranyl pyrophosphate isoprenoids. Recent studies suggest it also has growth inhibitory properties. Posttranslational farnesyl or geranylgeranylation of low molecular weight GTP-binding proteins such as RAS and RHO are thought to be an essential step in activation of phosphorylation cascades such as the RAS-RAF-1-MEK-1-MAPK/ERK pathway which stimulate cell proliferation. In this study, we evaluated lovastatin effects on meningioma cell proliferation and activation of the MEK-1-MAPK/ERK pathway. The effect of lovastatin on cell proliferation was assessed in eight human meningioma cell cultures stimulated by platelet derived growth factor (PDGF)-BB, cerebrospinal fluid (CSF), and fetal bovine serum (FBS). Concomitant lovastatin effects on phosphorylation/activation of mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) kinase (MEK-1) and MAPK/ERK were assessed by Western blot. Whether lovastatin acts via a mevalonate-dependent mechanism was also evaluated. Coadministration of lovastatin completely blocked PDGF-BB, CSF, and FBS stimulation of [3H]-thymidine incorporation and cell proliferation. Lovastatin inhibited PDGF-BB's stimulatory effect in a dose dependent manner. Concomitant with its growth inhibitory effects, lovastatin reduced phosphorylation/activation of MEK-1/2 in five meningiomas and MAPK/ERK in seven. Coadministration of mevalonate with lovastatin partially restored PDGF's mitogenic effect. Lovastatin is a potent inhibitor of meningioma cell proliferation which may act in part by reducing activation of MEK-1-MAPK/ERK pathway. Additional studies are warranted to assess whether lovastatin and similar HMG-CoA reductase inhibitors represent a new adjunctive chemotherapy for recurrent meningiomas.

    Title Evidence for Phosphatidylinositol 3-kinase-akt-p7s6k Pathway Activation and Transduction of Mitogenic Signals by Platelet-derived Growth Factor in Meningioma Cells.
    Date October 2002
    Journal Journal of Neurosurgery
    Excerpt

    OBJECT: The intracellular events transducing mitogenic signals from platelet-derived growth factor-beta (PDGFbeta) receptor tyrosine kinases are not precisely known. In this study the authors evaluated whether the phosphatidylinositol 3-kinase (PI3-K)-Akt-p70S6K pathway is expressed in meningiomas, regulates their growth, and transduces mitogenic signals of PDGF-BB. METHODS: Nine meningioma tumors obtained in humans were evaluated using Western blot analysis for phosphorylated (activated) Akt and phosphorylated p70S6K. Cells cultured from seven of these meningiomas were also screened using Western blot analysis for Akt and for phosphorylated Akt and p70S6K. The authors also evaluated whether PDGF-BB stimulation of meningioma cells was associated with the phosphorylation of Akt and p70S6K known to activate these kinases. In addition, the effects of wortmannin, an inhibitor of P13-K, on proliferation and activation of Akt and p70S6K in meningioma cells stimulated with PDGF-BB were evaluated. Western blots of lysates from meningiomas demonstrated phosphorylated Akt and p70S6K. Treatment with PDGF-BB stimulated phosphorylation of Akt and p70S6K in each meningioma cell culture. Wortmannin (500 and 1000 nM) significantly decreased PDGF-BB stimulation of meningioma cells (p < 0.001) while it reduced Akt and p70S6K phosphorylation but not mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) phosphorylation. CONCLUSIONS: These findings indicate that Akt and p70S6K are constitutively expressed and activated in meningioma cells and that the PI3-K-Akt-p70S6K pathway may participate in transduction of mitogenic signals in meningiomas independent of the Raf-1-MEK-1-MAPK/ERK cascade.

    Title Crystallization, Preliminary X-ray Analysis and Biophysical Characterization of Hpr Kinase/phosphatase of Mycoplasma Pneumoniae.
    Date June 2002
    Journal Acta Crystallographica. Section D, Biological Crystallography
    Excerpt

    The Mycoplasma pneumoniae HPr kinase/phosphatase (HPrK/P) is a member of a large family of enzymes which are central to carbon regulation in Gram-positive bacteria. The full-length M. pneumonia HPrK/P was crystallized from solutions of polyethylene glycol 8000 and KCl or NaCl which also contained the non-hydrolysable ATP analog adenosine 5'-[beta, gamma-methylene]triphosphate (AMPPCP). The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 117.1, b = 127.7, c = 170.7 A. A complete X-ray intensity data set has been collected and processed to 2.50 A resolution. The slow self-rotation function revealed the presence of a sixfold axis. Dynamic light-scattering (DLS) experiments indicated a molecular weight of 197 kDa for HPrK/P in the absence of AMPPCP and of 217 kDa in the presence of the ATP analog. Thus, the biophysical and crystallographic data suggest that HPrK/P is a functional hexamer that undergoes an ATP-binding-induced conformational change.

    Title Blunt Versus Penetrating Subclavian Artery Injury: Presentation, Injury Pattern, and Outcome.
    Date April 1999
    Journal The Journal of Trauma
    Excerpt

    BACKGROUND: Subclavian artery (SCA) injuries are rare vascular injuries and may be difficult to manage. The majority of SCA injuries are secondary to penetrating trauma. The purpose of this report is to examine the injury patterns, diagnostic and therapeutic approaches, and outcome of patients with blunt and penetrating SCA injuries. METHODS: Retrospective review RESULTS: Fifty-six patients sustained SCA injuries (25 blunt, 31 penetrating). SCA injury location was evenly distributed between the proximal, middle, and distal SCA after penetrating trauma; proximal injuries were rare (2 of 25) with blunt mechanisms. A radial arterial pulse deficit was present in only 3 of 25 blunt injuries and 9 of 31 penetrating injuries. Complications occurred more commonly in both groups of patients with initial systolic blood pressures less than 90 mm Hg. Survival was 76% in blunt and 81% in penetrating groups; limb salvage was similar (92% in blunt and 97% in penetrating groups). Complete brachial plexus injuries were more common with blunt injuries. CONCLUSION: SCA injuries are rare vascular injuries with an associated high morbidity and mortality, regardless of mechanism. Blunt mechanisms result in more middle and distal injuries and more frequent complete brachial plexus injuries. Complications are related to the hemodynamic status of the patient upon presentation, and not to mechanism of injury.

    Title Pulmonary Contusion in Children: Diagnosis and Management.
    Date December 1998
    Journal Southern Medical Journal
    Excerpt

    BACKGROUND: Pulmonary contusion (PC) is the most common injury identified in pediatric blunt chest trauma. The disagreement over management principles of children with PC may complicate care of these patients. METHODS: We reviewed the literature and our institutional experience. RESULTS: Pulmonary contusion is most often diagnosed by chest roentgenogram, with computed tomography of the chest reserved for more precise evaluation of the mediastinum and aorta. Hypoxemia and respiratory mechanical insufficiency are the most common causes of morbidity from early chest injury. Complications include pneumonia and the adult respiratory distress syndrome, which together may occur in up to one half of all cases. CONCLUSIONS: Early diagnosis, maintaining euvolemia, and selective mechanical ventilation may help to limit morbidity. Management guidelines based on the available literature may improve the care of these patients.

    Title Delayed Diagnosis of Blunt Duodenal Injury: an Avoidable Complication.
    Date October 1998
    Journal Journal of the American College of Surgeons
    Excerpt

    BACKGROUND: There is controversy about the impact on morbidity from delayed diagnoses of blunt hollow viscus injuries. A recent study suggested that the increased morbidity was primarily from delayed diagnosis of blunt duodenal injury (BDI). STUDY DESIGN: We studied the medical records from a 10-year period from June 1987 to June 1997 examining the data on 22,163 cases of blunt trauma. We assessed the incidence and consequences of delayed diagnoses of BDI, and identified preoperative factors associated with these delayed diagnoses. RESULTS: Thirty-five patients (0.2%) were identified in the retrospective study of the records from 22,163 blunt trauma patients to have sustained BDI. Of these, 25 patients (71%) were male. Ages ranged from 1 to 58 years (mean 18.8 years), and the predominant mechanism was motor vehicle accident in 18 patients (51%). Seven patients (20%) (group I) had a diagnostic delay of > 6 hours; 28 patients (80%) (group II) were diagnosed in < 6 hours. Six of the seven group I patients (86%) were evaluated initially with CT scans, and five (83%) showed findings suggestive of BDI. Among the 28 group II patients, 14 (50%) underwent initial diagnostic peritoneal lavage (DPL), and 14 (50%) had a CT scan. In seven of the group II patients (50%) who were initially evaluated by CT scan, there were findings suggestive of BDI. Diagnostic peritoneal lavage was initially equivocal (red blood cell count=5,000 to 100,000) in the remaining one group I patient compared with three of the group II patients who had DPL. Deterioration found on physical examinations prompted followup CT scans in 6 group I patients (86%), and the scans were diagnostic for BDI in all cases. CONCLUSIONS: Blunt duodenal injury is an uncommon entity. Despite the presence of suggestive CT and DPL findings, the diagnosis was delayed in 20% of the 35 patients whose records were examined in the study; this delayed diagnosis was associated with increased abdominal complications. Patients with persistent abdominal complaints and equivocal CT or DPL findings should undergo laparotomy or repeat CT scan evaluations.

    Title Postoperative Respiratory Complications in Ex-premature Infants After Inguinal Herniorrhaphy.
    Date October 1998
    Journal Journal of Pediatric Surgery
    Excerpt

    BACKGROUND/PURPOSE: The duration of postoperative cardiorespiratory monitoring of premature infants after inguinal herniorrhaphy is uncertain. Prolonged observation requiring hospital admission may be unnecessary and increases costs. METHODS: This study was a retrospective review of 191 inguinal herniorrhaphies performed between 1993 and 1996 at the Hermann Children's Hospital. The authors reviewed their experience to identify factors associated with postoperative apnea and bradycardia and determine a safe period of observation. RESULTS: Among 191 elective inguinal herniorrhaphies performed, 57 (29.8%) were in expremature infants (< or =60 weeks postconception). Five (8.8%) infants either failed extubation or were unable to extubate (group 1). The average age for this group was 41.0 +/- 1.2 weeks compared with 47.2 +/- 1.0 (P = .06) for those who were successfully extubated (group II). Preoperative apnea-bradycardia was found in four (80%) infants in group I compared with 32 (61.5%) in group II (P = 0.67). All group I and 21 (40.4%, P = .09) group II infants with a history of preoperative apnea required intubation for an average of 24.4 +/- 7.8 days and 8.2 +/- 2.4 days, respectively (P = .04). American Society of Anesthesia (ASA) scores were 2.6 +/- 0.4 for group I compared with 1.8 +/- 0.1 for group 11 (P = .01). The use of both intraoperative narcotics (three [60%] in group I v six [12%] in group II, P = .01]) and vecuronium (four [80%] in group I v 16 [31%] in group II, P = .03) were significantly more common in group I infants. Operating room time was 46.4 +/- 4.1 minutes for group I compared with 60.6 +/- 3.9 minutes for group II (P = .27). Postoperative apnea-bradycardia occurred in all five group I infants and two (3.8%, P = .001) group II infants. Group II infants were treated successfully with supplemental oxygen. CONCLUSIONS: All instances of postoperative apnea-bradycardia and laryngospasm occurred within 4 hours after operation without significant differences between groups. The risk of postoperative cardiorespiratory distress requiring reintubation in premature infants who undergo inguinal herniorrhaphy is not insignificant (8.8%). The judicious use of narcotics and vecuronium, and limiting patient selection to those with ASA score of less than 3 may lessen the need for reintubation. When present cardiorespiratory distress occurs early; therefore we recommend outpatient inguinal herniorrhaphy as a safe and cost-effective choice.

    Title Hollow Visceral Injury and Blunt Trauma.
    Date August 1998
    Journal The Journal of Trauma
    Excerpt

    BACKGROUND: The incidence of hollow viscus injury (HVI) after blunt trauma (BT) is variable, and differences between children and adults have not been well described. The purpose of this study is to determine the age-group-related incidence and characteristics of BT-associated HVI as well as the clinical markers and consequences of delayed diagnosis. METHODS: A 9-year trauma registry review of all patients with HVI. RESULTS: A large sample of patients (19,621) with BT were evaluated (2,550 < or = 14 years old; 17,070 > 14 years old). One hundred thirty-nine of 17,070 (0.8%) adults had HVI compared with 27 of 2,550 (1%) children. HVI occurred more frequently in the duodenum in children (11 of 27) compared with adults (17 of 139) (p < 0.05). Among patients with abdominal wall ecchymosis, 13.5% of children had HVI compared with 10.6% of adults. Delays in diagnosis of HVI occurred in 9 of 27 children compared with 10 of 139 adults (p < 0.0 5). Delayed diagnosis was associated with increased abdominal septic complications in both children (4 of 9) and adults (2 of 10) compared with diagnosis at presentation (p < 0.05). CONCLUSION: HVI occurs with a similar low frequency in both children and adults. Duodenal injuries are more common in pediatric BT patients. Abdominal wall ecchymosis is associated with increased HVI but is less predictive of HVI than previously described. Contrary to previous reports, delays in diagnosis are associated with increased morbidity.

    Title Sublabial, Transseptal, Transsphenoidal Approach to the Pituitary Region Guided by the Acustar I System.
    Date March 1998
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVE: Advances in imaging resolution have resulted in superior visualization of intracranial anatomy. Because of the inherent complexity of the surgical exposure of these lesions, intraoperative localizing techniques are required. Currently, C-arm fluoroscopy provides only two-dimensional localization for these anatomic structures. The recently described ACUSTAR I system, developed in conjunction with Codman and Shurtleff, Inc. (Randolph, Mass.), is an interactive, image-guided device that allows three-dimensional localization with a degree of accuracy previously unattainable. We assessed the clinical utility of the ACUSTAR I system for intraoperative spatial confirmation during transsphenoidal approaches to pituitary lesions. METHODS: Eight patients underwent transsphenoidal approaches to pituitary lesions with the assistance of the ACUSTAR I system. The spatial relationships were clinically judged intraoperatively by the surgeon and by use of traditional C-arm fluoroscopy and then were compared with the ACUSTAR I system results. RESULTS: In all eight patients, the ACUSTAR I system correctly displayed the surgical orientation and provided localization to within less than 1 mm. In two patients, this facilitated the redirection of an errant approach. No complications were associated with the use of this image-guided device. CONCLUSIONS: The ACUSTAR I system is useful in displaying accurate, three-dimensional anatomic relationships during transsphenoidal approaches to pituitary lesions. This system provides critical information intraoperatively to redirect errant approaches and prevent significant morbidity.

    Title The Importance of Pulsatile and Nonpulsatile Flow in the Design of Blood Pumps.
    Date November 1997
    Journal Artificial Organs
    Excerpt

    The traditional approach of total artificial heart (TAH) and ventricular assist device (VAD) development has been the mimicking of the native heart. Nonpulsatile flow using cardiopulmonary bypass has provided evidence of short-term physiologic tolerances. The design of nonpulsatile TAHs and VADs has eliminated the need for valves, flexing diaphragms, and large ventricular volumes. However, these devices require high efficiency power sources and reliable bearing seals or electromagnetic bearings while simultaneously attempting to avoid thromboemboli. The physiologic response to nonpulsatile flow is complex and variable. When compared to a pulsatile device, a nonpulsatile TAH or VAD needs to produce increased flow and higher mean intravascular pressures to maintain normal organ function. Despite its maintaining normal organ function, nonpulsatile flow does cause alterations in biochemical functions and organ specific blood flow. The combination of bioengineering superiority and the maintenance of physiologic homeostasis has directed future TAH and VAD research towards nonpulsatile systems.

    Title Registration of Head Volume Images Using Implantable Fiducial Markers.
    Date October 1997
    Journal Ieee Transactions on Medical Imaging
    Excerpt

    In this paper, we describe an extrinsic-point-based, interactive image-guided neurosurgical system designed at Vanderbilt University, Nashville, TN, as part of a collaborative effort among the Departments of Neurological Surgery, Computer Science, and Biomedical Engineering. Multimodal image-to-image (II) and image-to-physical (IP) registration is accomplished using implantable markers. Physical space tracking is accomplished with optical triangulation. We investigate the theoretical accuracy of point-based registration using numerical simulations, the experimental accuracy of our system using data obtained with a phantom, and the clinical accuracy of our system using data acquired in a prospective clinical trial by six neurosurgeons at four medical centers from 158 patients undergoing craniotomies to resect cerebral lesions. We can determine the position of our markers with an error of approximately 0.4 mm in X-ray computed tomography (CT) and magnetic resonance (MR) images and 0.3 mm in physical space. The theoretical registration error using four such markers distributed around the head in a configuration that is clinically practical is approximately 0.5-0.6 mm. The mean CT-physical registration error for the phantom experiments is 0.5 mm and for the clinical data obtained with rigid head fixation during scanning is 0.7 mm. The mean CT-MR registration error for the clinical data obtained without rigid head fixation during scanning is 1.4 mm, which is the highest mean error that we observed. These theoretical and experimental findings indicate that this system is an accurate navigational aid that can provide real-time feedback to the surgeon about anatomical structures encountered in the surgical field.

    Title Pulmonary Contusion: Are Children Different?
    Date September 1997
    Journal Journal of the American College of Surgeons
    Excerpt

    BACKGROUND: Pulmonary contusion (PC) is a common sequelae of blunt trauma in adults and children; previous reports suggest that children have more favorable outcomes because of differences in mechanisms of injury, associated injury, and physiologic response. Our objective was to determine whether children who sustain PC have different outcomes compared with similarly injured adults. STUDY DESIGN: Our Level I Trauma Registry was reviewed for a 4-year period and identified 251 consecutive patients who sustained PC. Their charts were reviewed retrospectively for demographics, injury mechanism, injury severity scores, associated injuries, and outcomes (measured by the need for intubation, ventilation days, pneumonia, acute respiratory distress syndrome, and death). Data are expressed as the mean +/- SEM. The Student's t-test was used to compare the groups. A p value less than 0.05 was considered significant. RESULTS: Of the study patients, 41 (16%) were children (ages 2-16, mean 10 years) and 210 (84%) were adults (ages 17-80, mean 34 years). The most common injury mechanisms in children were motor vehicle accidents (56%) and auto-pedestrian accidents (39%), but in adults, motor vehicle accidents (80%, p = 0.02) predominated. Injury severity score was not significantly different between groups (children, 26 +/- 2 and adults 25 +/- 1). Similarly, the incidence of associated injuries was not different between children and adults: head 78% versus 62%, abdomen 59% versus 43%, and skeletal fractures 41% versus 29%, respectively. Neither need for intubation, ventilator days, pneumonia, acute respiratory distress syndrome, or death differed significantly between groups. CONCLUSIONS: Although children and adults differ in regard to injury mechanism, their overall injury severity, associated injuries, and outcomes are quite similar. Thus, contrary to previous reports, children do not have a more favorable outcome after PC.

    Title Traumatic Lung Herniation.
    Date May 1997
    Journal The Annals of Thoracic Surgery
    Excerpt

    Traumatic lung herniation is a poorly described entity. An important factor in the etiology of these lesions is the relative lack of muscular support afforded by the anterior thorax. We report a case of blunt thoracic trauma complicated by an incarcerated lung herniation.

    Title Subarachnoid Hemorrhage: Diagnosis and Treatment.
    Date May 1997
    Journal Tennessee Medicine : Journal of the Tennessee Medical Association
    Title Control of the Artificial Heart.
    Date March 1997
    Journal Asaio Journal (american Society for Artificial Internal Organs : 1992)
    Excerpt

    The artificial heart (AH) is devoid of physiologic connections to the recipient's native feedback control loops. Control of an AH can be either passive or dynamic. Passive intrinsic control provides limited AH response to physiologic demands. Dynamic control requires the sensing of metabolic and hemodynamic signals and their incorporation into self-adjusting AH function. A single metabolic or hemodynamic parameter cannot provide sufficient data accurately to adjust AH pumping in response to varying blood flow demands. A combination of input control signals is required for reliable and flexible AH function. The selection of appropriate input control parameters and their incorporation into AH controller designs remains a critical step in the achievement of a permanent, totally implantable AH.

    Title Pulmonary Contusion: a Collective Review.
    Date December 1996
    Journal The American Surgeon
    Excerpt

    Pulmonary contusion is the most common injury identified in blunt chest trauma. Despite improvements in diagnostic imaging and critical care, the associated mortality has not appreciably changed over the last three decades. Parenchymal injury ultimately manifests as alveolar collapse and lung consolidation. Early detection and intervention toward minimizing injury progression provides the greatest chance for survival. Avoiding fluid overload, oxygen therapy, and a low threshold for mechanical ventilation are useful therapeutic guidelines. Complications include pneumonia and adult respiratory distress syndrome, which may occur in up to one half of all cases. Pulmonary contusion is a serious injury that may complicate patient management as well as pose a vital threat.

    Title A Technique for Interactive Image-guided Neurosurgical Intervention in Primary Brain Tumors.
    Date October 1996
    Journal Neurosurgery Clinics of North America
    Excerpt

    Interactive image-guided neurosurgical techniques allow safer and more complete cytoreduction of gliomas. This is most significant for low-grade tumors, whose configurations and margins are perhaps better appreciated by reference to registered MR images rather than by reliance on direct visualization using microscopic illumination. Spatially registered electro-physiologic recordings of intraoperative cortical stimulation to map language and motor function can increase the margin of safety for performing radical resections. By individualizing approaches and optimizing results, these technologies promise a new degree of standardization of outcome after resective surgery for all glial tumors.

    Title Evaluating Contrast-enhancing Brain Lesions in Patients with Aids by Using Positron Emission Tomography.
    Date October 1995
    Journal Annals of Internal Medicine
    Excerpt

    OBJECTIVE: To determine whether a noninvasive method for evaluating contrast-enhancing brain lesions in patients with the acquired immunodeficiency syndrome (AIDS) can accurately differentiate between lymphoma and nonlymphoma diagnoses. This method is based on Toxoplasma serologic testing and positron emission tomography. DESIGN: Prospective, nonrandomized, criterion-standard clinical study. SETTING: An academic center in the mid-southeastern United States. PATIENTS: 20 patients with AIDS and contrast-enhancing brain lesions. INTERVENTIONS: Positron emission tomographic scanning and Toxoplasma serologic testing. MAIN OUTCOME MEASURE: Diagnoses were confirmed by clinical response, autopsy, or brain biopsy. RESULTS: Eight patients had a confirmed diagnosis of toxoplasmosis, six had lymphoma, four had other diagnoses, and two were not evaluable. Seven of eight patients with toxoplasmosis had positron emission tomographic scans; all of these scans showed hypometabolic lesions consistent with a nonlymphoma diagnosis. The six patients with lymphoma all had hypermetabolic lesions on positron emission tomographic scans. The difference between these two sets of results was statistically significant (P < 0.001, Fisher exact test, two-tailed). The anti-Toxoplasma titer was greater than or equal to 1:4 in all patients with confirmed toxoplasmosis who had serologic testing and in three of six patients with lymphoma. CONCLUSIONS: Evaluating contrast-enhancing brain lesions in patients with AIDS by using Toxoplasma serologic testing and positron emission tomography can accurately guide therapy and obviate the need for most brain biopsies in these patients. A larger, national, multicenter study is needed to confirm our findings and to determine the effect of earlier diagnosis and treatment on morbidity and mortality in patients with AIDS and primary central nervous system lymphoma.

    Title Viral Myocarditis Leading to Cardiomyopathy: Do Cytokines Contribute to Pathogenesis?
    Date September 1993
    Journal Clinical Immunology and Immunopathology
    Excerpt

    Cardiotropic virus infection of mice typically produces florid myocardial inflammation and, in certain strains, elicits a chronic postinfectious autoimmune myocarditis. In humans, myocarditis may progress into cardiomyopathy manifested by interstitial fibrosis and myocyte hypertrophy in the absence of myocardial inflammation. Because of their pleiotropic effects, cytokines may provide a common link between connective tissue changes, myocardial injury, and cardiac autoimmunity. To explore such possibilities, histopathological and serological studies were performed on virus-infected mice which were or were not subject to cytokine manipulation. Mice infected with low doses of encephalomyocarditis virus exhibited little myocardial inflammation although myocyte hypertrophy and reactive fibrosis were common. Profound ultrastructural changes in the interstitium were observed through much of the noninflamed myocardium. B10.A mice which are resistant to the development of postinfectious autoimmune myocarditis developed severe autoimmune myocarditis when infected with Coxsackie virus B3 (CB3) and treated with bacterial lipopolysaccharide (LPS), tumor necrosis factor (TNF), or interleukin 1 (IL-1). B10.A mice given CB3, LPS, TNF, or IL-1 alone did not develop myocarditis and there was no evidence of autoimmune recognition of the heart. When CB3-infected A/J mice, which typically develop autoimmune sequelae to the infection, were treated with an IL-1 receptor antagonist, myocardial injury was diminished and heart antibody activity was reduced. These results suggest that TNF, IL-1, and possibly other cytokines contribute to myocardial pathogenesis and the induction of heart-specific autoimmunity. Further studies may lead to the development of cytokine-based therapeutic approaches to treating myocarditis and cardiomyopathy.

    Title A Universal System for Interactive Image-directed Neurosurgery.
    Date December 1992
    Journal Stereotactic and Functional Neurosurgery
    Excerpt

    Stereotactic methods confer great accuracy to intracranial target localization, but require strict adherence to a complex program of mechanical and computational maneuvers. A computerized, articulated, localizing 'arm' has been developed that frees the neurosurgeon of these constraints and provides a completely intuitive, 'user-friendly' interface. This universal system is independent of whatever localizing fiducial system is selected. The arm may be sterilized for intracranial use. A variety of intraoperative end effectors may be selected. The patient's CT/MR/PET scans are loaded into computer memory and a three-dimensional shaded surface wireframe diagram of the patient's head is displayed simultaneously with up to 3 independent sets of cross-referenced CT/MR/PET scan images on the intraoperative video screen. The arm's endpoint location and the directional vector are shown as cursors on the relevant scan slices, and change continuously as the surgeon moves the arm. Because the information is continuously updated, an unlimited number of targets and trajectories may be displayed throughout the operation. The arm has an ultimate design accuracy for end-point localization to within 0.1 mm throughout a target volume of 40 x 40 x 40 cm. The tested application accuracy of the first prototype model is 0.31 mm. In clinical use during 30 surgeries, its real-world application accuracy is 0.9 mm. This system provides stereotactic accuracy and universally compatible, intuitive, interactive operation.

    Title In Vivo Deposition of Myosin-specific Autoantibodies in the Hearts of Mice with Experimental Autoimmune Myocarditis.
    Date July 1992
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    Experimental autoimmune myocarditis (EAM) is elicited in certain strains of mice by immunizing with mouse cardiac myosin. Concomitant with the onset of myocardial inflammation is the induction of circulating IgG antibodies to myosin. To further examine the role of myosin in disease, both EAM-susceptible (A/J) and EAM-resistant (B10.A) mice were immunized with myosin emulsified in CFA and examined for myocardial inflammation and IgG deposition. Myocarditis was common in susceptible, but not resistant strain mice. IgG deposition was extensive in A/J mice, but modest in B10.A mice, when compared to controls given adjuvant alone. Localization was independent of inflammatory or necrotic lesions. A spot ELISA indicated that antimyosin IgG antibody-secreting cells were present in the myocardial infiltrate and likely contributed to antibody localization. Antibody was eluted from the hearts of immunized animals and found to react strongly with normal heart tissue by indirect immunohistochemistry. This reactivity was not completely absorbed by skeletal muscle, indicating that some of the antibody was heart-specific. Western immunostaining demonstrated that eluates from immunized A/J and B10.A mice possessed anti-myosin antibody activity; similar reactivity was not observed in eluates from control mice of either strain. Comparison of heart reactivity with syngeneic and allogeneic tissue suggests that although myosin immunization elicits homologous antibody in both strains, each may recognize distinct epitopes. These findings strongly suggest that cardiac myosin or a myosin-like determinant is expressed on the surface of normal mouse myocytes.

    Title Heart-specific Autoantibodies Can Be Eluted from the Hearts of Coxsackievirus B3-infected Mice.
    Date January 1992
    Journal Clinical and Experimental Immunology
    Excerpt

    This study was undertaken to determine if immunoglobulin G (IgG) antibodies could be eluted from the hearts of mice with Coxsackievirus B3-induced autoimmune myocarditis and to characterize the immunoreactivity of any elutable autoantibodies. Susceptible (A/J) and resistant (B10.A) mice were administered the virus or the control treatment and killed at various times after treatment. Acid eluates from pooled heart tissue from each treatment group and each time were tested for IgG reactivity with normal heart tissue by immunohistochemistry and with normal heart extracts by Western immunostaining. Eluates from infected A/J mice reacted strongly with syngeneic heart and modestly with syngeneic skeletal muscle tissue. Eluates from infected B10.A or control mice of either strain exhibited little reactivity with either tissue. Tissue reactivity was similar when allogeneic tissue was used as the substrate. Eluates from infected A/J mice recognized the heavy chain of cardiac myosin and several other cardiac antigens by Western immunostaining while eluates from the other treatment groups exhibited little or no reactivity with any normal heart constituents. These results indicate that in vivo IgG deposition occurs in the hearts of mice with post-infectious autoimmune myocarditis and that the specificity of these antibodies is similar to that reported for serum from animals with this disease. The mechanism(s) leading to myocardial IgG deposition and its possible role in pathogenesis remain to be elucidated.

    Title Elution of Autoantibodies from the Hearts of Coxsackievirus-infected Mice.
    Date November 1991
    Journal European Heart Journal
    Excerpt

    Circulating heart-reactive antibodies are commonly reported in myocarditis and cardiomyopathy patients. While these observations support the hypothesis that autoimmune mechanisms may be involved in pathogenesis, such evidence is largely circumstantial. The current studies demonstrate that heart-reactive antibodies can be eluted from the hearts of infected Coxsackievirus B3-infected A/J mice with post-infectious autoimmune myocarditis, but not from the hearts of infected B10.A mice which are resistant to autoimmune myocarditis. The eluted antibodies recognize fewer cardiac antigens than are recognized by circulating antibodies. These results provide an opportunity to examine the role of autoantibodies in the pathogenesis of chronic myocarditis.

    Title Preliminary Report on Adrenal Medullary Grafting from the American Association of Neurological Surgeons Graft Project.
    Date April 1991
    Journal Progress in Brain Research
    Title Combined Chylothorax, Chylopericardium, and Cranial Vena Cava Syndrome in a Dog with Thymoma.
    Date February 1991
    Journal Journal of the American Veterinary Medical Association
    Excerpt

    A dog was examined because of anorexia and development of submandibular, sternal, and forelimb edema. Physical examination revealed engorged jugular veins and engorged blood vessels of the conjunctivae and nictitating membranes. Thoracic radiography revealed pleural and pericardial effusions, later identified as chyle. Contrast angiography revealed an intravascular mass, later identified as thymoma, in the cranial vena cava.

    Title Adrenal Medullary Tissue Transplantation in Parkinson's Disease: a Review.
    Date December 1990
    Journal Advances in Neurology
    Title Alterations in Prealbumin Concentration After Adrenal Autotransplantation for Parkinson's Disease.
    Date June 1990
    Journal Experimental Neurology
    Excerpt

    The cerebrospinal fluid of eight patients with Parkinson's disease who underwent adrenal medullary autotransplantation was analyzed using SDS-polyacrylamide gel electrophoresis. A protein, subsequently identified as prealbumin, was noted to change in concentration over the intraoperative to 18-month postoperative time course. The qualitative changes observed on visual inspection were confirmed and quantified using laser densitometry. The concentration of prealbumin increased by an average of 90% when the intraoperative and 12-month samples were compared. This increase persisted at 18 months. The ratio of prealbumin to albumin also increased from intraoperative to 12 months by an average of 56%. This suggests that the increases in PA are the result of choroid plexus activation rather than a nonspecific breakdown of the blood-brain barrier. Given the association of prealbumin with other nervous system diseases, as well as its known ability to bind multiple substances, these findings may have important implications. Alterations in prealbumin may be responsible for the improvement seen in some patients who receive adrenal medullary autotransplants. Alternatively, prealbumin may be implicated in the pathophysiology of Parkinson's disease.

    Title Long-term Prevention of Toxin-induced Damage by Neural Grafts.
    Date June 1989
    Journal Progress in Brain Research
    Title Adrenal Medullary Transplantation to the Caudate Nucleus in Parkinson's Disease. Initial Clinical Results in 18 Patients.
    Date June 1989
    Journal Archives of Neurology
    Excerpt

    Results from a pilot study of adrenal medullary autotransplantation for Parkinson's disease are presented. Eighteen patients were studied; 12 were followed up for 1 year, and 6 were followed up for 6 months. Four of 12 patients showed distinct improvement in the signs and symptoms of their disease, as assessed using the Columbia Rating Scale, at 1 year; none showed distinct deterioration. The 6 patients who were followed up for only 6 months were an average of 20 years older and generally more severely affected. None distinctly improved. Morbidity was considered to be minor and transient among the first 12 patients, while 4 of the last 6 patients experienced alteration in mental status lasting as long as several months. This problem has led us to conclude that older patients with preexisting cognitive impairment should not be included in future studies until the benefits are more clearly established. However, we believe that the distinct and persistent improvement seen in some of the younger patients warrants the initiation of a well-designed, randomized, and controlled trial of adrenal medullary autotransplantation for the purpose of confirming these results and assessing the effect of the procedure on the natural progression of Parkinson's disease.

    Title Alteration of Kainic Acid and Quinolinic Acid Toxicity by Neostriatal Transplants in Vitro.
    Date May 1989
    Journal Neuroscience Letters
    Excerpt

    Mature (greater than 21 days in vitro) organotypic corticostriatal cultures prepared from newborn rat brain were incubated in either kainic acid (KA) 10(-3) M or quinolinic acid (QUIN) 10(-3) M for up to 48 h. Other identical cultures were similarly incubated immediately after they had received one or two additional explants of neonatal striatal tissue placed beside each corticostriatal culture. The cultures incubated with either KA or QUIN in the presence of the neonatal striatal tissue showed better preservation than cultures incubated with KA or QUIN alone. Results suggest that the neonatal striatal explants or 'transplants' afford some protective effect against the toxicity or either KA or QUIN.

    Title Striatal Grafts Provide Sustained Protection from Kainic and Quinolinic Acid-induced Damage.
    Date January 1989
    Journal Experimental Neurology
    Excerpt

    Grafts of neonatal striatal tissue were placed into the striata of adult rats. When challenged immediately with intrastriatal injections of either kainic or quinolinic acid, excitotoxic damage was prevented. Thirty days later these same graft recipients received another injection of excitotoxin. The intrastriatal grafts continued to mitigate toxin-induced damage. It is hypothesized that the grafted cells not only survive, but that they may continue to elaborate some substance or substances that prevent excitotoxin-induced injury for at least 30 days. Previous investigations indicated that grafts of neonatal striatal tissue can protect the recipient striatum from kainic acid toxicity. In the following study it is demonstrated that such grafts also protect the striatum from quinolinic acid, an endogenous excitotoxin which induces kainate-like neuronal degeneration and has been implicated in the pathogenesis of Huntington's disease. It is postulated that the salutary effect of striatal grafting may be sufficiently long lasting to mitigate a chronic toxic insult. Such grafting may therefore represent a therapy for Huntington's disease and other neurodegenerative disorders in which an endogenous or exogenous toxin has been implicated as the pathogenetic agent.

    Title Perioperative Management for Transplant of Autologous Adrenal Medulla to the Brain for Parkinsonism.
    Date November 1988
    Journal Anesthesiology
    Title Neonatal Striatal Grafts Prevent Lethal Syndrome Produced by Bilateral Intrastriatal Injection of Kainic Acid.
    Date September 1986
    Journal Brain Research
    Excerpt

    It is reported that unilateral grafts of neonatal striatal tissue protect the recipient from the lethal aphagia and adipsia produced by bilateral intrastriatal injection of 10 nmol of kainic acid in rats. It is shown that neither adult striatum nor neonatal tissue from other sites have the same lifesaving effect and that the salutary effect of the graft is dependent upon graft survival. Grafts from a histoincompatible donor are apparently rejected, leading to the death of the recipient. Cyclosporine inhibits rejection thereby enabling recipient survival. It is postulated that the graft exerts a neurohumoral influence that protects the striatum from the toxic effect of kainate.

    Title Canine Basilar Artery Contractions Mediated by 5-hydroxytryptamine1a Receptors.
    Date July 1986
    Journal The Journal of Pharmacology and Experimental Therapeutics
    Excerpt

    A series of 11 agents was analyzed at both 5-hydroxytryptamine1A (5-HT1A) sites labeled by [3H]-8-hydroxy-2-(N,N-dipropylamino)tetralin and total 5-HT1 binding sites labeled by [3H]-5-HT in rat brain membranes. Three distinct patterns of relative inhibition were noted. First, drugs such as 8-hydroxy-2-(N,N-dipropylamino)tetralin n-(3-acetylaminophenyl)piperazine hydrochloride, 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]-1,2-benziso-thiazol-3 -(2H)one-1,1-dioxidehydrochloride] and buspirone display 1.0 to 15 nM potency for the 5-HT1A subpopulation of 5-HT1 binding sites but are more than two orders of magnitude less potent at total 5-HT1 sites. Secondly, 5-methoxy-N,N-dimethyltryptamine and methysergide are approximately one order of magnitude more potent at 5-HT1A than total 5-HT1 sites. In the third group, 5-HT, d-lysergic acid diethylamide, 1-(m-trifluoromethylphenyl)piperazine, 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyrimidinyl) 1H indole, quipazine and pirenperone are essentially equipotent at both 5-HT1A and 5-HT1 sites. Thus, the 5-HT1A binding site has a pharmacological profile which, depending on the agents studied, could be significantly different from the pharmacological profile derived from total 5-HT1 binding. Drug interactions were also analyzed with canine basilar artery segments using 5-HT, 10 putative serotonergic agonists and a selective 5-HT2 antagonist, pirenperone. The maximal contraction was obtained using 5-HT (Cmax = 6.6 +/- 0.6 g). However, each of the 10 other putative 5-HT agonists elicited a less forceful contraction of the canine basilar artery.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Pituitary Transplantation: Cyclosporine Enables Transplantation Across a Minor Histocompatibility Barrier.
    Date June 1986
    Journal Neurosurgery
    Excerpt

    Pituitary glands from neonatal donors were transplanted to the median eminence of hypophysectomized adult rats. Rats with transplants were then treated for 2 weeks with the immunosuppressive drug cyclosporine. For 5 weeks thereafter, blood was drawn at regular intervals for determination of serum thyroxine, prolactin, and luteinizing hormone. Cyclosporine-treated recipients of grafts with minor histocompatibility differences had normal levels of thyroxine and prolactin, whereas untreated animals did not. In addition, the treated animals responded to oophorectomy with a marked elevation in serum luteinizing hormone. This evidence indicates that cyclosporine enables successful transplantation across a minor histocompatibility barrier. It also suggests that these grafts interact with the hypothalamus. Transplantation across a major histocompatibility barrier was unsuccessful even in the presence of cyclosporine.

    Title Cerebral Arterial Spasm.
    Date January 1986
    Journal Clinical Neurosurgery
    Title Calcium Channel Antagonism by Pizotifen.
    Date July 1985
    Journal Journal of Neurology, Neurosurgery, and Psychiatry
    Excerpt

    Pizotifen is a clinically effective anti-migraine agent with potent anti-serotonin and anti-histamine properties. Pizotifen is equipotent in blocking contractions of the canine basilar artery induced by serotonin, norepinephrine or calcium chloride. As a result, the primary action of pizotifen in the canine basilar artery system appears to be calcium channel blockade and not selective antagonism of serotonin or norepinephrine. Calcium channel blocking ability may be related to the clinical efficacy of pizotifen in the treatment of migraine.

    Title Visual Function Following Optic Canal Decompression Via Craniotomy.
    Date June 1985
    Journal Journal of Neurosurgery
    Excerpt

    Visual function was assessed in 15 eyes of 11 patients who underwent unilateral (seven patients) or bilateral (four patients) optic canal decompression for presumed compressive optic neuropathies. Both immediate and long-term postoperative vision was evaluated in all eyes. Over 90% of the eyes that had undergone nerve decompression had either the same or improved visual acuity and visual field immediately following surgery. In this group of patients there were no deaths and there was only one postoperative complication, a transient dysphasia caused by an epidural hematoma that was evacuated. Long-term follow-up evaluations revealed that most of the eyes retained their immediate postoperative visual function or showed gradual visual improvement with time. The results of this series as well as a review of the available literature indicate that optic canal decompression via craniotomy can be a safe procedure and that it appears to have lasting visual benefit in many patients.

    Title Pituitary Transplantation: Part 1. Successful Reconstitution of Pituitary-dependent Hormone Levels.
    Date May 1985
    Journal Neurosurgery
    Excerpt

    Neonatal or adult pituitary glands were transplanted to the median eminence of adult rats of the same or a histoincompatible inbred strain. The hormonal status of 39 transplanted rats and of control animals was evaluated by serial determination of serum prolactin and thyroxine. Grafts of neonatal tissue to adults of the same strain resulted in normal postoperative hormone levels. This indicates not only that pituitary grafts had survived, but also that the transplants were under hypothalamic control. Grafts of adult tissue were less successful. The prolactin value was lower, but still within the normal range, whereas the thyroxine value was lower than normal, suggesting that viable pituitary tissue had survived but was not under hypothalamic control. Transplantation across a histocompatibility barrier was uniformly unsuccessful. Postoperative prolactin levels were low and thyroxine levels were not significantly different from those in hypophysectomized controls.

    Title Role of Calcium Antagonists in Cerebral Arterial Spasm.
    Date February 1985
    Journal The American Journal of Cardiology
    Excerpt

    Spasm of the large cerebral arteries at the base of the brain causes delayed ischemic neurologic deficits in approximately 30% of patients after a subarachnoid hemorrhage from an intracranial aneurysm. In vitro chamber studies have shown that both dog and human large cerebral artery segments contract to a variety of vasoactive agents, and the dog and human segments are remarkedly similar in their responses. The source of calcium necessary to initiate contraction was found to be extracellular for large cerebral arteries. In contrast, systemic arteries such as the femoral artery use a bound intracellular pool of calcium for contraction. The calcium antagonists nifedipine and nimodipine were found to selectively inhibit the contractions of large cerebral arteries but not the femoral artery. In vivo experiments demonstrated that both nifedipine and nimodipine, given sublingually, would prevent and reverse cerebral arterial spasm in the dog after a subarachnoid hemorrhage. Nimodipine was found to be more potent, both in the chamber and in the live dog experiments. Nimodipine significantly decreased the occurrence of severe neurologic deficits from spasm alone in a multi-institutional, prospective, double-blind, randomized, placebo-controlled trial.

    Title Relative Potency and Selectivity of Calcium Antagonists Used in the Treatment of Migraine.
    Date June 1984
    Journal Headache
    Title The Calcium Antagonist Properties of Cyproheptadine: Implications for Antimigraine Action.
    Date April 1984
    Journal Neurology
    Excerpt

    Cyproheptadine is equipotent (IC50 = 41 to 45 nM) in blocking contractions of canine basilar artery segments induced by serotonin, norepinephrine, potassium, or calcium. Methysergide and amitriptyline display variable potencies in inhibiting contractions depending on the initiating agent. Propranolol, at concentrations to 10 micromolar, had minimal effect on vessel contractions. We conclude that the primary action of cyproheptadine in preventing induced contractions of the canine basilar artery is antagonism of calcium channels. This action is unique among drugs used for migraine prophylaxis and may have important implications for the treatment of headache and other neurologic disorders.

    Title Calcium Channel Antagonist Binding Sites Labeled by 3h-nimodipine in Human Brain.
    Date December 1983
    Journal Journal of Neurosurgery
    Excerpt

    In vitro binding of 3H-nimodipine to human brain membranes is demonstrated in this study. This binding was specific and saturable, and had an apparent affinity constant (KD) of 0.27 nM. The maximal number of binding sites for 3H-nimodipine was 5.8 pmoles/gm wet weight of human frontal cortex. The binding was shown to be dependent on calcium, with half-maximal stimulation obtained at 3 X 10(-5) M CaCl2. Other 1,4-dihyropyridine calcium antagonists were shown to be competitive antagonists of 3H-nimodipine binding. In contrast, the calcium antagonists, verapamil and diltiazem, had complex interactions with 3H-nimodipine binding. These results represent the first identification of 3H-calcium antagonist binding sites in human brain, and they confirm that various calcium antagonist drugs may differ with respect to both their potency and their molecular site of action.

    Title Occluded but Nonthrombosed Internal Carotid Artery: an Indication for Endarterectomy.
    Date September 1983
    Journal Ajnr. American Journal of Neuroradiology
    Excerpt

    The indications for carotid endarterectomy are sometimes imprecise. Total occlusion of the internal carotid artery has often implied irreversibility. Carotid thromboendarterectomy was performed on eight patients who on angiography had a complete occlusion of proximal internal carotid artery but showed antegrade opacification of the infraophthalmic carotid siphon. Direct magnification, delayed radiography, and subtraction were used on all patients. In five of eight patients, normal antegrade cervical internal carotid blood flow was restored. The possible restoration of the occluded internal carotid artery lumen offers a viable alternative to bypass surgery in selected cases.

    Title Serotonin-induced Contraction of Canine Basilar Artery: Mediation by 5-ht1 Receptors.
    Date April 1983
    Journal Brain Research
    Excerpt

    Serotonin and related agonists cause a marked contraction of canine basilar artery segments. These contractions can be inhibited by a variety of serotonergic antagonists. Absolute potencies of both serotonin agonists and antagonists in chamber contraction studies significantly correlate (P less than 0.01) with their potencies for 5-HT1, but not 5-HT2, receptors as defined by central nervous system radioligand binding studies. Serotonin-induced contractions of canine basilar artery segments appear to be mediated by 5-HT1 receptors.

    Title Cerebral Arterial Spasm--a Controlled Trial of Nimodipine in Patients with Subarachnoid Hemorrhage.
    Date April 1983
    Journal The New England Journal of Medicine
    Excerpt

    We enrolled 125 neurologically normal patients with intracranial aneurysms in a multi-institution, prospective, double-blind, randomized, placebo-controlled trial within 96 hours of their subarachnoid hemorrhage, to determine whether treatment with the calcium blocker nimodipine would prevent or reduce the severity of ischemic neurologic deficits from arterial spasm. A deficit from cerebral arterial spasm that persisted and was severe or caused death by the end of the 21-day treatment period occurred in 8 of 60 patients given placebo and in 1 of 56 given nimodipine (P = 0.03, Fisher's exact test). Analysis of the amount of basal subarachnoid blood on pre-entry CAT scans in patients with deficits from spasm showed that an increase in subarachnoid blood was not associated with a worse neurologic outcome among patients who received nimodipine, unlike the situation in patients given a placebo. There were no side effects from nimodipine. We conclude that nimodipine should be given to patients who are neurologically normal after subarachnoid hemorrhage in order to reduce the occurrence of severe neurologic deficits due to cerebral arterial spasm.

    Title Carotid Endarterectomy in the Prevention of Stroke.
    Date December 1982
    Journal Comprehensive Therapy
    Title Carotid Endarterectomy: a Prospective Study of Its Efficacy and Safety.
    Date August 1981
    Journal Medicine
    Title Microsurgical Endarterectomy of the Intracranial Vertebral Artery for Vertebrobasilar Transient Ischemic Attacks.
    Date May 1981
    Journal Neurosurgery
    Excerpt

    Two patients who had typical vertebrobasilar transient ischemic attacks (TIAs) that were refractory to anticoagulation with dicumarol and to antiplatelet therapy with aspirin and/or dipyridamole are described. Angiography revealed in both patients a stenotic atherosclerotic plaque of the intracranial vertebral artery between the posterior and anterior inferior cerebellar arteries. At operation, the first patient had an atherosclerotic plaque extending into the basilar artery, and no endarterectomy was attempted. The second patient had a 1-cm localized plaque that was removed successfully from the vertebral artery. Neither patient sustained a neurological deficit as a result of the operation. The patient whose plaque was not removed at operation continues to have vertebrobasilar TIAs and suffered a brain stroke 2 weeks after operation. The patient whose plaque was removed at operation continues to be free of TIAs 8 months later, and angiography performed 3 months after operation showed a widely patent vertebral artery. A portion of the intracranial vertebral artery has now been shown to be accessible to endarterectomy using the operating microscope. Angiography is helpful in determining this accessibility preoperatively.

    Title Language Lateralization and Unilateral Ect.
    Date September 1980
    Journal The British Journal of Psychiatry : the Journal of Mental Science
    Title Sphenoidal Pneumosinus Dilatans with Bilateral Optic Nerve Meningiomas. Case Report.
    Date October 1979
    Journal Journal of Neurosurgery
    Excerpt

    The authors report a case of bilateral progressive visual loss in a patient with a radiological diagnosis of sphenoidal pneumosinus dilatans. At craniotomy, bilaterally symmetrical meningiomas of the optic nerve sheaths were found at the intracranial optic foramina. Reported cases of sphenoidal pneumosinus dilatans as well as bilateral meningiomas of the optic nerve sheaths are reviewed. The possible mechanisms of visual loss in pneumosinus dilatans and the management of nerve sheath and planum sphenoidale meningiomas are discussed.

    Title Cerebral Arterial Spasm: Part 9. In Vitro Effects of Nifedipine on Serotonin-, Phenylephrine-, and Potassium-induced Contractions of Canine Basilar and Femoral Arteries.
    Date August 1979
    Journal Neurosurgery
    Excerpt

    We performed in vitro experiments with a small volume chamber to determine the inhibitory effect of nifedipine on serotonin-, phenylephrine-, and potassium-induced contractions of canine basilar and femoral arteries. Nifedipine, an inhibitor of the influx of extracellular calcium into smooth muscle cells, was found to be a sensitive inhibitor of contractions of the basilar artery induced by all three agents. In contrast, nifedipine did not significantly inhibit the serotonin- and phenylephrine-induced contractions of the femoral artery but did inhibit potassium-induced contractions of the femoral artery. Calcium-induced contractions of the basilar artery were also inhibited by nifedipine. These experiments demonstrate a relatively selective effect of nifedipine on the basilar artery, and a mechanism to explain this selective effect is postulated.

    Title Cerebral Arterial Spasm: Part 10. Reversal of Acute and Chronic Spasm in Dogs with Orally Administered Nifedipine.
    Date August 1979
    Journal Neurosurgery
    Excerpt

    In vivo experiments in dogs demonstrated angiographically that the subarachnoid injection of blood produced cerebral arterial apasm both immediately after the injection of blood and 2 days later. The sublingual adminstration of nifedipine reversed both the acute and the delayed cerebral arterial spasm. In addition, sublingual administration of nifedipine 20 minutes before the subarachnoid injection of blood prevented the acute spasm.

    Title Effects of Nifedipine on Artificially Induced Femoral and Basilar Artery Contraction in Vitro and Reversal of Acute and Chronic Vertebral Basilar Spasm by Orally Administered Nifedipine in Dogs.
    Date May 1979
    Journal Neuroradiology
    Title Cerebral Arterial Spasm: A Discussion of Present and Future Research.
    Date October 1978
    Journal Neurosurgery
    Excerpt

    The author presents a discussion of research on cerebral arterial spasm. Arterial smooth muscle contraction, receptor and relaxation mechanisms are presented in the context of what is known about cerebral arterial spasm and the biochemistry of vascular smooth muscle. Several new experimental approaches are suggested and a theoretical biochemical basis for the idea that damage to the artery alone could cause cerebral arterial spasm is postulated. Methods of determining cerebral arterial spasm and the need for a quantitative, in vivo method are discussed and the question of an irreversible stage of cerebral arterial spasm is considered. Finally, the problems associated with the delivery of a potentially successful treatment to the cerebral arterial smooth muscle cells are examined.

    Title Cerebral Arterial Spasm. Part 7: In Vitro Effects of Alpha Adrenergic Agents on Canine Arteries from Six Anatomical Sites and Six Blocking Agents on Serotonin-induced Contractions of the Canine Basilar Artery.
    Date October 1976
    Journal Surgical Neurology
    Excerpt

    In vitro experiments were performed using a small volume chamber to determine the contractile activity of several adrenergic agents on arteries from six locations of the canine vascular bed. Cumulative log-dose response curves were obtained for epinephrine, norepinephrine, phenylephrine and dopamine. It was found that the basilar and internal carotid arteries responded much less to these agents than did the mesenteric, renal and femoral arteries. Six blocking agents including nitroprusside were tested to determine their effect on the response of the canine basilar artery to log-dose additions of serotonin, prostaglandin F2alpha and KC1. Another chamber was developed to study the differential effect of nitroprusside and papaverine when placed on the luminal side versus the adventitial (cerebrospinal fluid) side of the basilar artery during a sustained contraction with serotonin. A theoretical treatment of cerebral arterial spasm following a subarachnoid hemorrhage is presented.

    Title Cerebral Arterial Spasm. Part 8: The Treatment of Delayed Cerebral Arterial Spasm in Human Beings.
    Date October 1976
    Journal Surgical Neurology
    Excerpt

    Three patients who had neurological deficits from delayed cerebral arterial spasm following rupture of posterior communicating artery aneurysms were treated with continuous, simultaneous, intravenous injections of phenylephrine and nitroprusside. The results were determined by cerebral angiography before and after treatment. A dramatic increase in the cross-sectional area of the large cerebral arteries was found after treatment. The clinical implications of this treatment are discussed.

    Title Cerebral Arterial Spasm. Part 4: in Vitro Effects of Temperature, Serotonin Analogues, Large Nonphysiological Concentrations of Serotonin, and Extracellular Calcium and Magnesium on Serotonin-induced Contractions of the Canine Basilar Artery.
    Date July 1976
    Journal Journal of Neurosurgery
    Excerpt

    In vitro experiments were performed using a small volume chamber to study serotonin-induced contractions of the canine basilar artery. Temperature was found to have a profound effect on the artery's response to serotonin. Raising the temperature to 40 degrees C (104 degrees F) increased the maximum response by 20% and lowering the temperature by 10 degrees C caused a 40% reduction in the maximum contraction. Cumulative log-dose response curves for analogues of serotonin demonstrated a high degree of specificity for the serotonin receptor and large nonphysiological concentrations of serotonin caused relaxation of the contracted artery. Extracellular calcium was shown to be an absolute requirement for serotonin-induced contractions. Extracellular magnesium, in contrast, was shown to inhibit serotonin-induced contractions.

    Title Cerebral Arterial Spasm. Part 5: in Vitro Contractile Activity of Vasoactive Agents Including Human Csf on Human Basilar and Anterior Cerebral Arteries.
    Date July 1976
    Journal Journal of Neurosurgery
    Excerpt

    In vitro experiments were performed with a small volume chamber to determine the contractile activity of various vasoactive agents on human basilar and anterior cerebral arteries. Cumulative log-dose response curves were obtained for most of the agents tested including serotonin and three different prostaglandins; many of these curves were found to be similar to curves previously obtained with canine cerebral arteries. It was concluded from these similarities that canine cerebral arteries are a good in vitro model for studying human cerebral arterial spasm. It was also demonstrated that human cerebrospinal fluid, collected up to 17 days after a subarachnoid hemorrhage from patients with clinical and angiographic evidence of cerebral arterial spasm, would cause large, dose-dependent contractions in human anterior cerebral arteries.

    Title Modulation of Adrenergic Transmission by Acetylcholine.
    Date January 1976
    Journal Clinical and Experimental Pharmacology & Physiology
    Title Proceedings: Study of Cerebral Arterial Spasm. In Vitro Contractile Activity of Various Vasoactive Agents on the Human Basilar and Anterior Cerebral Arteries.
    Date October 1975
    Journal Journal of Neurology, Neurosurgery, and Psychiatry
    Title Modulation by Acetylcholine of Adrenergic Transmission in the Rabbit Ear Artery.
    Date October 1975
    Journal British Journal of Pharmacology
    Excerpt

    1. Low concentrations of acetylcholine (4 times 10(-11) and 1 times 10(-10) M) increase the vasoconstrictor response of the isolated ear artery of the rabbit to stimulation of the periarterial sympathetic nerves. Higher concentrations (4 times 10(-8) M and greater) decrease the response. 2. Low concentrations of acetylcholine (1 times 10(-11) and 1 times 10(-10) M) increase the stimulation-induced efflux of radioactivity from artery segments previously incubated with [3H]-noradrenaline. Higher ocncentrations (3 times 10(-8) M and greater) decrease the efflux. 3. Neither atropine nor hexamethonium affects the facilitatory action of low concentrations of acetylcholine on adrenergic transmission in the rabbit ear artery. 4. Atropine antagonizes the inhibitory effect of higher concentrations of acetylcholine on adrenergic transmission.

    Title Effects of the Muscarinic Agonist Mcn-a-343 on the Release by Sympathetic Nerve Stimulation of (3h)-noradrenaline from Rabbit Isolated Ear Arteries and Guinea-pig Atria.
    Date April 1975
    Journal British Journal of Pharmacology
    Title Acidic Proteins in Cerebral and Hepatic Microsomes: Isolation of a Protein (agl-40) Compounds Primarily of Glutamyl, Aspartyl and Lysyl Residues with Hematin-binding Properties.
    Date December 1974
    Journal Voprosy Biokhimii Mozga
    Title Cerebral Arterial Spasm. 1. In Vitro Contractile Activity of Vasoactive Agents on Canine Basilar and Middle Cerebral Arteries.
    Date April 1974
    Journal Journal of Neurosurgery
    Title Cerebral Arterial Spasm. 2. In Vitro Contractile Activity of Serotonin in Human Serum and Csf on the Canine Basilar Artery, and Its Blockage by Methylsergide and Phenoxybenzamine.
    Date April 1974
    Journal Journal of Neurosurgery
    Title Cerebral Arterial Spasm. 3. In Vivo Intracisternal Production of Spasm by Serotonin and Blood and Its Reversal by Phenoxybenzamine.
    Date April 1974
    Journal Journal of Neurosurgery
    Title Techniques for Studying Adrenergic Transmitter Release in an Isolated Perfused Artery.
    Date October 1973
    Journal Cardiovascular Research
    Title Comparison of Effects of Six Cholinomimetic Drugs on Inhibition of Uptake of 3 H-( )-noradrenaline by Guinea-pig Atria.
    Date September 1973
    Journal British Journal of Pharmacology
    Title Effects of Acetylcholine on Vasoconstriction and Release of 3 H-noradrenaline in Response to Sympathetic Nerve Stimulation in the Isolated Artery of the Rabbit Ear.
    Date May 1973
    Journal British Journal of Pharmacology
    Title Effects of Cholinomimetics on Adrenergic Transmission.
    Date November 1972
    Journal Japanese Journal of Pharmacology
    Title Effects of Mcn-a-343 and Dmpp on the Uptake and Release of 3 H-noradrenaline by Guinea-pig Atria.
    Date November 1972
    Journal British Journal of Pharmacology
    Title The Dextro-isomer of Noradrenaline As a False Transmitter.
    Date September 1972
    Journal The Journal of Pharmacy and Pharmacology
    Title The Shades of Green.
    Date September 1970
    Journal The Journal of the Indiana State Medical Association
    Title Interaction Between Histamine and Monoamine Oxidase Inhibitors.
    Date October 1969
    Journal The Journal of Pharmacy and Pharmacology
    Title Effective Office Management of Obesity.
    Date October 1968
    Journal The Journal of the Indiana State Medical Association

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