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  1. Article: Stage of infection with

    Wherry, Taylor L T / Heggen, Mark / Shircliff, Adrienne L / Mooyottu, Shankumar / Stabel, Judith R

    Frontiers in veterinary science

    2023  Volume 10, Page(s) 1117591

    Abstract: Introduction: Macrophages are the preferential target of : Methods: This study aimed to characterize expression of early and late endosomal markers Rab5 and Rab7, respectively, within CD68+ macrophages in frozen mid-ileum sections harvested from cows ...

    Abstract Introduction: Macrophages are the preferential target of
    Methods: This study aimed to characterize expression of early and late endosomal markers Rab5 and Rab7, respectively, within CD68+ macrophages in frozen mid-ileum sections harvested from cows at different stages of natural paratuberculosis infection. Additionally, factors of vitamin D
    Results and discussion: Cows with clinical paratuberculosis had significantly greater macrophage and MAP burden overall, as well as intracellular MAP. Total expression of Rab5 within macrophages was reduced in clinical cows; however, Rab5 and MAP colocalization was significantly greater in this group. Intracellular Rab7 colocalization with MAP was not detected in subclinical or Johne's Disease negative (JD-) control cows but was present in clinical cows. Additionally, macrophage CYP27B1 expression was significantly reduced in clinical cows. Taken together, the results from this study show disparate patterns of expression for key mediators in intracellular MAP trafficking and vitamin D metabolism for cows at different stages of paratuberculosis.
    Language English
    Publishing date 2023-02-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2834243-4
    ISSN 2297-1769
    ISSN 2297-1769
    DOI 10.3389/fvets.2023.1117591
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Stage of infection with Mycobacterium avium subsp. paratuberculosis impacts expression of Rab5, Rab7, and CYP27B1 in macrophages within the ileum of naturally infected cows

    Taylor L. T. Wherry / Mark Heggen / Adrienne L. Shircliff / Shankumar Mooyottu / Judith R. Stabel

    Frontiers in Veterinary Science, Vol

    2023  Volume 10

    Abstract: IntroductionMacrophages are the preferential target of Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of ruminant paratuberculosis. Uptake of pathogens by intestinal macrophages results in their trafficking through endosomal ... ...

    Abstract IntroductionMacrophages are the preferential target of Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of ruminant paratuberculosis. Uptake of pathogens by intestinal macrophages results in their trafficking through endosomal compartments, ultimately leading to fusion with an acidic lysosome to destroy the pathogen. MAP possesses virulence factors which disrupt these endosomal pathways. Additionally, levels of serum vitamin D3 have proven relevant to host immunity. Dynamics of endosomal trafficking and vitamin D3 metabolism have been largely unexplored in bovine paratuberculosis.MethodsThis study aimed to characterize expression of early and late endosomal markers Rab5 and Rab7, respectively, within CD68+ macrophages in frozen mid-ileum sections harvested from cows at different stages of natural paratuberculosis infection. Additionally, factors of vitamin D3 signaling and metabolism were characterized through expression of vitamin D3 activating enzyme 1α-hydroxylase (CYP27B1), vitamin D3 inactivating enzyme 24-hydroxylase (CYP24A1), and vitamin D3 receptor (VDR) within CD68+ ileal macrophages.Results and discussionCows with clinical paratuberculosis had significantly greater macrophage and MAP burden overall, as well as intracellular MAP. Total expression of Rab5 within macrophages was reduced in clinical cows; however, Rab5 and MAP colocalization was significantly greater in this group. Intracellular Rab7 colocalization with MAP was not detected in subclinical or Johne's Disease negative (JD-) control cows but was present in clinical cows. Additionally, macrophage CYP27B1 expression was significantly reduced in clinical cows. Taken together, the results from this study show disparate patterns of expression for key mediators in intracellular MAP trafficking and vitamin D metabolism for cows at different stages of paratuberculosis.
    Keywords Mycobacterium avium subsp. paratuberculosis ; macrophage ; Rab5 ; Rab7 ; vitamin D ; CYP27B1 ; Veterinary medicine ; SF600-1100
    Subject code 630
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: The assessment and management of chronic pain in children.

    Chambliss, C Robert / Heggen, Judith / Copelan, David N / Pettignano, Robert

    Paediatric drugs

    2002  Volume 4, Issue 11, Page(s) 737–746

    Abstract: Chronic pain in children and adolescents is frequently misdiagnosed by caregivers. It is not treated until it results in the loss of routine ability and function. Chronic pain is often associated with underlying diseases commonly seen in childhood, ... ...

    Abstract Chronic pain in children and adolescents is frequently misdiagnosed by caregivers. It is not treated until it results in the loss of routine ability and function. Chronic pain is often associated with underlying diseases commonly seen in childhood, including sickle cell disease, malignancy, rheumatologic disorders, inflammatory bowel disease, trauma, and states where there is no identifiable etiology. Chronic pain differs from acute pain in that it serves no useful function. Untreated or under-treated chronic pain will result in the unnecessary suffering of the patient, disruption of family routine, and cohesiveness and restriction of the child's daily activities, thereby increasing long-term disability. Accurate and repeated assessment of chronic pain is required for therapy to be effective. Assessment of chronic pain in children is difficult due to their developing cognitive abilities. The assessment of childhood pain varies with the child's age, type of pain, situation, and prior painful experiences. Assessment tools such as the Varni-Thompson Pediatric Pain Questionnaire and the Visual Analog Scale are helpful for both the patient and physician in helping to identify situations that precipitate pain, to rate the level of pain and determine if therapy has been effective. Documentation of pain assessments and the effectiveness of interventions in the medical record should be included as a routine part of all patient records. Most caregivers have extensive experience in the treatment of acute pain in children but are often not comfortable with the management of complicated and chronic pain states. The therapy for chronic pain in children is multifactorial. It can include agents from multiple classes of pharmacologic agents (nonsteroidal anti-inflammatory drugs, opioids, tricyclic antidepressants, and antineuroleptics) nonconventional therapies (acupuncture and pressure and aromatherapy), as well as herbal and homeopathic remedies.
    MeSH term(s) Acute Disease ; Adolescent ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antidepressive Agents/therapeutic use ; Chemotherapy, Adjuvant ; Child ; Chronic Disease ; Complementary Therapies ; Depression/drug therapy ; Depression/etiology ; Humans ; Narcotics/therapeutic use ; Pain/complications ; Pain/drug therapy ; Pain Measurement
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal ; Antidepressive Agents ; Narcotics
    Language English
    Publishing date 2002-07-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1492748-2
    ISSN 1179-2019 ; 1174-5878
    ISSN (online) 1179-2019
    ISSN 1174-5878
    DOI 10.2165/00128072-200204110-00005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5205: Show issues Location:
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  4. Article ; Online: Systemic hypertension associated with venovenous extracorporeal membrane oxygenation for pediatric respiratory failure.

    Heggen, Judith A / Fortenberry, James D / Tanner, April J / Reid, Christopher A / Mizzell, Dana W / Pettignano, Robert

    Journal of pediatric surgery

    2004  Volume 39, Issue 11, Page(s) 1626–1631

    Abstract: Background/purpose: Arterial hypertension (HTN) is common in neonates on venoarterial (VA) extracorporeal membrane oxygenation (ECMO), but HTN in pediatric venovenous (VV) ECMO has not been well described. The authors noted HTN in their VV ECMO ... ...

    Abstract Background/purpose: Arterial hypertension (HTN) is common in neonates on venoarterial (VA) extracorporeal membrane oxygenation (ECMO), but HTN in pediatric venovenous (VV) ECMO has not been well described. The authors noted HTN in their VV ECMO experience and hypothesized that HTN was associated with fluid status, steroid use, and renal insufficiency.
    Methods: Records of 50 patients receiving VV ECMO for respiratory failure were reviewed. HTN was defined as systolic blood pressure greater than 95th percentile for age for > or =1 hour, unresponsive to sedation/analgesia. Hypertensive index (HI) is defined as total hypertensive hours per total ECMO hours. Fluid status was estimated by a fluid index (FI = total fluid balance during ECMO per ECMO hours per weight).
    Results: Forty-seven of 50 patients (94%) had HTN. Median HI was 0.21 (range, 0.01 to 1.0). Thirteen patients had renal insufficiency, 39 received steroids, and 23 received continuous venovenous hemofiltration (CVVH). There was no association between HI and FI, steroid use, or renal insufficiency. Thirty-three patients were treated for HTN, often requiring multiple agents. Bleeding complicated the course of 18 patients, and HI was significantly higher in those patients (P = .03). HI was not different between survivors (37 of 39 with HTN) and nonsurvivors (10 of 11 with HTN).
    Conclusions: Hypertension is a common complication associated with VV ECMO with unclear etiology. HTN was frequently difficult to control. This study emphasizes the need for the development of treatment protocols to decrease the incidence, severity, and associated morbidity. Improved insight into the etiology of HTN associated with pediatric VV ECMO, including evaluation of the renin-angiotensin system, would help guide therapy.
    MeSH term(s) Adolescent ; Child ; Child, Preschool ; Extracorporeal Membrane Oxygenation/adverse effects ; Extracorporeal Membrane Oxygenation/methods ; Humans ; Hypertension/etiology ; Hypertension/prevention & control ; Infant ; Respiratory Insufficiency/therapy
    Language English
    Publishing date 2004-06-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80165-3
    ISSN 1531-5037 ; 0022-3468
    ISSN (online) 1531-5037
    ISSN 0022-3468
    DOI 10.1016/j.jpedsurg.2004.07.007
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    Zs.A 607: Show issues Location:
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  5. Article: Primary use of the venovenous approach for extracorporeal membrane oxygenation in pediatric acute respiratory failure.

    Pettignano, Robert / Fortenberry, James D / Heard, Micheal L / Labuz, Michele D / Kesser, Kenneth C / Tanner, April J / Wagoner, Scott F / Heggen, Judith

    Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

    2003  Volume 4, Issue 3, Page(s) 291–298

    Abstract: Objectives: To describe a single center's experience with the primary use of venovenous cannulation for supporting pediatric acute respiratory failure patients with extracorporeal membrane oxygenation (ECMO).: Design: Retrospective chart review of ... ...

    Abstract Objectives: To describe a single center's experience with the primary use of venovenous cannulation for supporting pediatric acute respiratory failure patients with extracorporeal membrane oxygenation (ECMO).
    Design: Retrospective chart review of all patients receiving extracorporeal life support at a single institution.
    Setting: Pediatric intensive care unit at a tertiary care children's hospital.
    Patients: Eighty-two patients between the ages of 2 wks and 18 yrs with severe acute respiratory failure.
    Interventions: ECMO for acute respiratory failure.
    Measurements and main results: From January 1991 until April 2002, 82 pediatric patients with acute respiratory failure were cannulated for ECMO support. Median duration of ventilation before ECMO was 5 days (range, 1-17 days). Sixty-eight of these patients (82%) initially were placed on venovenous ECMO. Fourteen patients were initiated and remained on venoarterial support, including six in whom venovenous cannulae could not be placed. One patient was converted from venovenous to venoarterial support due to inadequate oxygenation. Venoarterial patients had significantly greater alveolar-arterial oxygen gradients and lower PaO(2)/FIO(2) ratios than venovenous patients (p <.03). Fifty-five of 81 venovenous patients received additional drainage cannulae (46 of 55 with an internal jugular cephalad catheter). Thirty-five percent of venovenous patients and 36% of venoarterial patients required at least one vasopressor infusion at time of cannulation (p = nonsignificant); vasopressor dependence decreased over the course of ECMO in both groups. Median duration on venovenous ECMO for acute hypoxemic respiratory failure was 218 hrs (range, 24-921). Venovenous ECMO survivors remained cannulated for significantly shorter time than nonsurvivors did (median, 212 vs. 350 hrs; p =.04). Sixty-three of 82 ECMO (77%) patients survived to discharge-56 of 68 venovenous ECMO (81%) and nine of 14 venoarterial ECMO (64%).
    Conclusions: Venovenous ECMO can effectively provide adequate oxygenation for pediatric patients with severe acute respiratory failure receiving ECMO support. Additional cannulae placed at the initiation of venovenous ECMO could be beneficial in achieving flow rates necessary for adequate oxygenation and lung rest.
    MeSH term(s) Acute Disease ; Adolescent ; Age Factors ; Child ; Child, Preschool ; Data Interpretation, Statistical ; Extracorporeal Membrane Oxygenation/adverse effects ; Extracorporeal Membrane Oxygenation/methods ; Female ; Humans ; Infant ; Infant, Newborn ; Intensive Care Units, Pediatric ; Male ; Respiratory Distress Syndrome, Newborn/mortality ; Respiratory Distress Syndrome, Newborn/therapy ; Respiratory Insufficiency/mortality ; Respiratory Insufficiency/therapy ; Retrospective Studies ; Time Factors
    Language English
    Publishing date 2003-07
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2052349-X
    ISSN 1947-3893 ; 1529-7535
    ISSN (online) 1947-3893
    ISSN 1529-7535
    DOI 10.1097/01.PCC.0000074261.09027.E1
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    Zs.A 5600: Show issues Location:
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  6. Article ; Online: Diffuse alveolar hemorrhage in pediatric hematopoietic cell transplant patients.

    Heggen, Judith / West, Carla / Olson, Ellen / Olson, Thomas / Teague, Gerald / Fortenberry, James / Yeager, Andrew M

    Pediatrics

    2002  Volume 109, Issue 5, Page(s) 965–971

    Abstract: Objective: Diffuse alveolar hemorrhage (DAH) is defined as a syndrome of hypoxia, dyspnea, infiltrates on chest radiograph, and bloody fluid on successive bronchoalveolar lavages without apparent infection. Minimal experience has been reported with DAH ... ...

    Abstract Objective: Diffuse alveolar hemorrhage (DAH) is defined as a syndrome of hypoxia, dyspnea, infiltrates on chest radiograph, and bloody fluid on successive bronchoalveolar lavages without apparent infection. Minimal experience has been reported with DAH after hematopoietic cell transplant (HCT) in children. We reviewed the incidence, management and outcome of DAH in a pediatric HCT population.
    Methods: Retrospective review of 138 patients undergoing allogeneic (n = 89) or autologous (n = 49) HCT at a referral children's medical center between January 1996 and April 2000.
    Results: Seven (5.1%) of 138 patients met criteria for DAH; all were allogeneic recipients. Mean age of DAH patients was 11 years (range: 1.4-15.2). Median onset of DAH following HCT was day 24 (range: 10-50), median day of engraftment day 20 and white blood cell count 0.54 x 10(9)/L (range: < 0.1-7.03), with no difference between survivors and nonsurvivors. All patients developed clinical respiratory failure and 6 required intubation, with PaO(2)/fraction of inspired oxygen <200. Patients were intubated a median of 12 days (range: 1-75). All patients experienced >1 episode of bleeding and 3 patients required reintubation after successful extubation resulting from recurrent DAH. Bronchoalveolar lavage fluid cultures were negative for viruses, bacteria and fungi. All DAH patients received steroids. Three patients died with progressive pulmonary failure and other organ system involvement. Four of 7 DAH patients (57%) survived to discharge, but 3 died from disease relapse at days 116, 138, and 273 post-HCT.
    Conclusion: DAH occurred more frequently in allogeneic HCT recipients compared with autologous recipients. Onset of DAH coincided closely with white blood cell engraftment. Although associated with significant respiratory failure and need for mechanical ventilation, HCT patients can survive DAH.
    MeSH term(s) Adolescent ; Bronchoalveolar Lavage ; Burkitt Lymphoma/therapy ; Child ; Child, Preschool ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hemoptysis/diagnosis ; Hemoptysis/etiology ; Hemorrhage/diagnosis ; Hemorrhage/etiology ; Humans ; Infant ; Lung Diseases/diagnosis ; Lung Diseases/etiology ; Male ; Pneumonia/diagnosis ; Pneumonia/etiology ; Pulmonary Alveoli ; Retrospective Studies ; Transplantation, Autologous ; Transplantation, Homologous
    Language English
    Publishing date 2002-04-30
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 207677-9
    ISSN 1098-4275 ; 0031-4005
    ISSN (online) 1098-4275
    ISSN 0031-4005
    DOI 10.1542/peds.109.5.965
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