19 results on '"Christopher M. McKinney"'
Search Results
2. Total Lightning Observations of Supercells over North Central Texas
- Author
-
Christopher M. McKinney, Lawence D. Carey, and Gregory R. Patrick
- Abstract
s part of a collaborative research project between Texas A&M; University and the NOAA/NWS Fort Worth/Dallas Weather Forecast Office, total lightning observations from Vaisala’s Dallas-Fort Worth (DFW) Lightning Detection and Ranging (LDAR II) network have been used to supplement Doppler radar measurements in the diagnosis of thunderstorm updraft strength and analysis of severe weather potential. More specifically, initial observations of severe convection over north-central Texas for three case dates have shown that total lightning flash extent density (FED) and gridded source density peaked prior to, or increased during reported severe weather events. Two lightning holes were observed with one supercell, and numerous FED notches were noted with other cells that likely indicated the updraft region of the thunderstorms. These signatures in the FED corresponded to weak echo regions on the KFWS WSR-88D radar reflectivity data. Additionally, lightning appendages developed for both right- and left- deviant cells prior to shifts in radar-inferred cell track, indicating a possible method for prediction of right or left hand deflections in supercell motion. A cell embedded within a linear MCS also developed a large notch in the FED data on its rear flank that persisted for over 25 min and preceded a severe wind report, indicating another potential forecasting application of total lightning data.
- Published
- 2021
3. Incorporating genetic counseling into the evaluation of pediatric bone marrow failure
- Author
-
Christopher M. McKinney, Taizo A Nakano, Roger Giller, Kaylee Dollerschell, Kami Wolfe Schneider, and Alexandra Suttman
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Genetic counseling ,Molecular genetic testing ,Bone marrow failure ,Anemia, Aplastic ,Genetic Counseling ,Hematopoietic stem cell transplantation ,Bone Marrow Failure Disorders ,medicine.disease ,Leukemia, Myeloid, Acute ,Myelodysplastic Syndromes ,Etiology ,medicine ,Humans ,Aplastic anemia ,Child ,Intensive care medicine ,business ,Genetics (clinical) ,Exome sequencing ,Genetic testing - Abstract
The timely identification of germline genetic causes of pediatric bone marrow failure (BMF) impacts medical screening practices, family counseling, therapeutic decision-making, and risk of progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). At diagnosis, treatment decisions need to be made quickly to mitigate risks associated with profound cytopenias. As genetic testing options are rapidly evolving, an efficient multi-disciplinary approach and algorithm, including early involvement of a genetics team, is needed to expedite diagnosis and therapeutic decision-making. This process aids in the identification of appropriate candidates for molecular genetic testing. We present our single center experience reviewing the implementation of genetic counseling and a diagnostic and therapeutic algorithm used to guide genetic evaluation of pediatric BMF. Disease-specific next-generation sequencing (NGS) panels were most often pursued in patients who presented with a clinical phenotype consistent with a known inherited BMF syndrome and when trying to reduce incidental or uninformative results. Broader BMF NGS panels were most often utilized when unable to narrow the suspected etiology to a single disorder. Whole exome sequencing helped with optimizing treatment decision-making in higher risk children with BMF who required expedited hematopoietic stem cell transplantation. The experience has led to improvements to our process for evaluating patients with BMF.
- Published
- 2021
4. Metabolic abnormalities in G6PC3-deficient human neutrophils result in severe functional defects
- Author
-
John Murphy, Daniel R. Ambruso, Angelina Baroffio, Alexander D. Tran, Michael Ellison, Julie A. Reisz, Christopher M. McKinney, Natalie J. Briones, and Angelo D'Alessandro
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Neutropenia ,Neutrophils ,G6PC3 ,Granulocyte ,Compound heterozygosity ,medicine.disease_cause ,Phagocytes, Granulocytes, and Myelopoiesis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,medicine ,Congenital Bone Marrow Failure Syndromes ,Humans ,Missense mutation ,Child ,Congenital Neutropenia ,Mutation ,biology ,business.industry ,Hematology ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Glucose-6-Phosphatase ,biology.protein ,business ,030217 neurology & neurosurgery ,Glucose 6-phosphatase - Abstract
Severe congenital neutropenia type 4 (SCN-4) is an autosomal recessive condition in which mutations in the G6PC3 gene encoding for the catalytic 3 subunit of glucose-6-phosphatase-β result in neutropenia, neutrophil dysfunction, and other syndromic features. We report a child with SCN-4 caused by compound heterozygous mutations in G6PC3, a previously identified missense mutation in exon 6 (c.758G>A[p.R235H]), and a novel missense mutation in exon 2 (c.325G>A[p.G109S]). The patient had recurrent bacterial infections, inflammatory bowel disease, neutropenia, and intermittent thrombocytopenia. Administration of granulocyte colony–stimulating factor (G-CSF) resolved the neutropenia and allowed for detailed evaluation of human neutrophil function. Random and directed migration by the patient’s neutrophils was severely diminished. Associated with this were defects in CD11b expression and F-actin assembly. Bactericidal activity at bacteria/neutrophil ratios >1:1 was also diminished and was associated with attenuated ingestion. Superoxide anion generation was
- Published
- 2020
5. Hematopoietic Cell Transplantation for Congenital Dyserythropoietic Anemia: A Report from the Pediatric Transplant and Cellular Therapy Consortium
- Author
-
Hemalatha G. Rangarajan, Joseph R. Stanek, Hisham Abdel-Azim, Arunkumar Modi, Ann Haight, Christopher M. McKinney, Daniel J. McKeone, David K. Buchbinder, Emmanuel Katsanis, Ghada A. Abusin, Ibrahim Ahmed, Jason Law, Jorge Galvez Silva, Kanwaldeep K. Mallhi, Lauri M. Burroughs, Niketa Shah, Peter J. Shaw, Robert Greiner, Shalini Shenoy, Michael A. Pulsipher, and Rolla Abu-Arja
- Subjects
Transplantation ,Transplantation Conditioning ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology ,Child ,Anemia, Dyserythropoietic, Congenital ,Retrospective Studies - Abstract
Hematopoietic cell transplantation (HCT) is the sole curative option for congenital dyserythropoietic anemia (CDA), a rare type of hemolytic anemia characterized by anemia, ineffective erythropoiesis, and secondary hemochromatosis. In this retrospective multicenter study, we report the outcomes of children with CDA who underwent HCT at participating Pediatric Transplantation and Cellular Therapy Consortium centers. Clinical information on HCT and associated outcomes was collected retrospectively using a common questionnaire. Data were analyzed using descriptive statistics and appropriate analysis. Eighteen patients with CDA who underwent allogeneic HCT between 2002 and 2020 were identified. The majority of patients (n = 13) had CDA type II, and the remainder had either CDA type I (n = 2) or CDA of unknown type (n = 3). Mutations were identified in 7 patients (39%), including SEC23B in 5, GATA1 in 1, and abnormality of chromosome 20 in 1. Thirteen patients had evidence of iron overload pre-HCT and received chelation therapy for a median duration of 10 months (range, 2 months to 17 years) pre-HCT. The median age at the time of HCT was 5.5 years (range, 0.7 to 26 years). Donors were HLA-matched (sibling, 4; unrelated, 10) and mismatched (haploidentical, 1; unrelated, 3). Graft sources were bone marrow in 15 patients, umbilical cord blood in 2 patients, or both in 1 patient. Conditioning included busulfan-based myeloablative (67%), fludarabine-based reduced-intensity (27%), or nonmyeloablative (6%) regimens. Five patients developed veno-occlusive disease, and 4 had viral reactivation. The cumulative incidence of acute graft-versus-host disease (GVHD) was 33%, and that of chronic GVHD was 22%. Four patients (22%) experienced graft failure; all engrafted following either a second HCT (n = 2) or third HCT (n = 2) but sustained considerable morbidities (3 GVHD, 1 death, 2 viral reactivation). With a median follow-up of 3.2 years (range, 0.6 to 14 years)), the 2-year overall survival, event-free survival (EFS), and GVHD-free EFS were 88% (95% confidence interval [CI], 73% to 100%), 65% (95% CI, 45% to 92%), and 60% (95% CI, 40% to 88%), respectively. Univariate analysis did not identify any patient- or transplantation-related variables impacting outcomes. Our study indicates that HCT can be curative for patients with CDA. Strategies such as aggressive chelation, use of preconditioning therapy, and early HCT in the presence of a suitable donor before comorbidities occur are needed to improve engraftment without increasing the risk for toxicity and mortality.
- Published
- 2022
6. Autoimmune cytopenias following allogeneic hematopoietic stem cell transplant in pediatric patients: Response to therapy and late effects
- Author
-
Roger Giller, Jessica Knight-Perry, Michael R. Verneris, Christopher M. McKinney, Ralph Quinones, and Jane Koo
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Graft vs Host Disease ,Gastroenterology ,Hypogammaglobulinemia ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Refractory ,Internal medicine ,ABO blood group system ,medicine ,Humans ,Child ,Retrospective Studies ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Daratumumab ,Infant ,Hematology ,medicine.disease ,Prognosis ,Transplantation ,Survival Rate ,Oncology ,030220 oncology & carcinogenesis ,Case-Control Studies ,Child, Preschool ,Hematologic Neoplasms ,Pediatrics, Perinatology and Child Health ,Rituximab ,Female ,Anemia, Hemolytic, Autoimmune ,Autoimmune hemolytic anemia ,business ,030215 immunology ,medicine.drug ,Follow-Up Studies - Abstract
BACKGROUND Autoimmune cytopenias (AICs) are rare, but serious complications of allogeneic hematopoietic cell transplantation (allo-HSCT). PROCEDURE We performed a case-control study using 20 pediatric AIC cases and 40 controls, matched by stem cell source and primary indication comparing clinical and transplant characteristics, treatment, outcomes, and late effects. RESULTS Cases were more likely to be human leukocyte antigen mismatched (P = 0.04). There was no difference in conditioning regimen, serotherapy use, graft-versus-host disease (GVHD) prophylaxis, incidence of acute or chronic GVHD, ABO compatibility, infections, and donor engraftment. The median time to AIC onset was 219 days (range, 97-1205 days) and AIC resolution was 365 days (range, 10 days to 2737.5 days). First-line therapies for AIC patients most commonly included corticosteroids (75%) and rituximab (55%). Only 25% of patients responded to first-line treatment. At a median of 611.5 days from last rituximab dose, 82.5% patients were still receiving intravenous immune globulin for hypogammaglobulinemia compared with 2.5% of controls (P
- Published
- 2020
7. A Quality Initiative to Decrease Time to Antibiotics in Children with Sickle Cell Disease and Fever
- Author
-
Anne Gillespie, Christopher M. McKinney, Rebecca Coughlin, Joanne M. Hilden, Rachelle Nuss, Dawn Law, Kathleen Montgomery, Amy Caruso-Brown, Lauren Tytler, and Anna Brouwer
- Subjects
medicine.medical_specialty ,business.industry ,medicine.drug_class ,Antibiotics ,MEDLINE ,Process improvement ,Psychological intervention ,Building and Construction ,Disease ,Triage ,Functional asplenia ,Individual QI Projects from Single Institutions ,Emergency medicine ,medicine ,Outpatient clinic ,business - Abstract
Introduction: Children with sickle cell disease (SCD) are at increased risk for sepsis secondary to functional asplenia. Timely administration of antibiotics, within 60 minutes of triage, is a national indicator of quality SCD care in the United States. However, there are no reports demonstrating the feasibility of doing so in the outpatient hematology–oncology clinic setting. Local Problem: At baseline, in our pediatric hematology–oncology outpatient center, just 10% of children with SCD and fever received timely antibiotics. Methods: We implemented a process improvement initiative for children with SCD and fever with the aim of ≥90% receiving timely antibiotics. We enacted interventions focused on general clinic processes from check-in to antibiotics and population-specific interventions, including an intravenous access protocol, notification/communication among staff members, and design of an electronic order set. Results: The percentage of children receiving timely antibiotics improved from 10% to 77% with successful maintenance following the interventions. Residual delays are due to nonexpeditious order placement and difficult intravenous access. Conclusion: Improving the timely administration of antibiotics in the outpatient hematology–oncology clinic setting for children with SCD and fever is possible. Achieving at least 90% timely antibiotics for children with SCD and fever in the outpatient clinic setting will require ongoing efforts at expeditious order placement and intravenous access.
- Published
- 2020
8. Hematopoietic Cell Transplantation for Congenital Dyserythropoietic Anemia: A Report from the Pediatric Transplant and Cellular Therapy Consortium (PTCTC)
- Author
-
Emmanuel Katsanis, Arunkumar Modi, Hemalatha G. Rangarajan, Kanwaldeep K. Mallhi, Ibrahim Ahmed, Joseph Stanek, Daniel J. McKeone, Ghada Abusin, Robert J. Greiner, Ann E. Haight, Shalini Shenoy, Lauri S Burroughs, Jorge Galvez Silva, David Buchbinder, Jason Law, Rolla Abu-Arja, Peter J. Shaw, Christopher M. McKinney, Michael A. Pulsipher, and Hisham Abdel-Azim
- Subjects
Oncology ,medicine.medical_specialty ,Pediatric transplant ,Hematopoietic cell ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Transplantation ,Cell therapy ,Internal medicine ,medicine ,business ,Congenital dyserythropoietic anemia - Abstract
Introduction Congenital dyserythropoietic anemias (CDA) are a rare group of hereditary disorders characterized by anemia, ineffective erythropoiesis, and secondary hemochromatosis. While some CDA patients respond to interferon α therapy (type I CDA) or splenectomy (type II CDA), others are dependent on chronic red cell transfusions lifelong. Hematopoietic cell transplant (HCT), remains the only curative option for this disease. In 39 patients reviewed by the European Society for Blood and Marrow Transplant (EBMT), graft rejection (GR) was 12% (1-23%), the 3-year overall survival (OS) and event free survival (EFS) were 71% (55-87%) and 45% (45-63%) respectively1. A trend towards higher incidence of GR and severe (Grade III-IV) acute graft versus host disease (GvHD) was observed in patients with iron overload and unrelated donor HCT but these risk factors were not statistically significant1. We report the outcomes in 17 children with CDA who underwent HCT at participating Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) centers. Methods Clinical information on transplant and associated outcomes were collected retrospectively after IRB approval using a common questionnaire. Data were analyzed using descriptive statistics. Comparisons between groups were made using Fisher's exact tests. Survival estimates and corresponding 95% confidence intervals were performed using the Kaplan-Meier method. Results Seventeen patients (11 males) with CDA were eligible by diagnosis and underwent HCT from 2002-2019. The median age at diagnosis was 0.7 (range: 0.2 - 14) years. A majority (n=12) of patients had CDA type II while the remainder either had CDA type I (n=2) or were unknown (n=3). Twelve (71%) patients had evidence of iron overload by biopsy or imaging and 11 received pre-HCT chelation. Three of the 12 patients had liver fibrosis confirmed by biopsy. Thirteen patients had splenomegaly and four underwent splenectomy prior to HCT. Three patients received pre-HCT immunosuppressive therapy (PTIS). Median age at the time of HCT was 5.5 (range: 0.7 - 15) years. The median interval between diagnosis and HCT was 3.8 (range 0 - 12.3) years. Most patients received myeloablative busulfan-based conditioning (n=12); however, 5 patients received nonmyeloablative (n=1) or reduced intensity (n=4) fludarabine-based conditioning regimens. Donor sources included HLA matched sibling (n=3), matched unrelated (n=9), haploidentical (n=1) and mismatched unrelated (n=4) donors. Graft source was bone marrow in all but 2 patients who received umbilical cord blood. The median total nucleated cell (TNC) dose for bone marrow grafts was 6.0 (range: 3.4- 20.6) x 108/kg. Cord blood recipients received a TNC dose of 3.8 x 107 and 4.8 x 107/kg. Five (29%) patients developed acute GvHD grade II-IV, with one patient with grade III-IV acute GvHD (5.8%). Post-HCT complications included veno-occlusive disease (n=3), acute kidney injury (n=1), congestive cardiac failure (n=1), thrombotic microangiopathy (n=1), CMV viremia requiring therapy (n=2), mucormycosis (n=1), streptococcal pneumonia (n=1), recurrent clostridium difficle colitis (n=1), and parvovirus infection (n=1). Four patients developed chronic GvHD (23.5%; 2 limited and 2 extensive). Characteristics and outcomes of the four patients (23.5%) who developed GR are shown in Table 1. With a median follow-up of 3.4 (range: 0.08 - 14) years; fourteen patients are alive. Three patients died from respiratory failure due to adenovirus, congestive cardiac failure and extensive chronic GvHD post 2nd HCT. The 2-year OS, EFS and GvHD-free-rejection-free survival of the entire cohort (95% confidence interval) were 87% (72-100%), 64% (44 -92%), and 58% (39- 88%), respectively (Figure 1). Due to limited sample size, we did not find any patient or HCT-related factors that were associated with GR, OS or GvHD. Conclusion HCT can be curative for patients with CDA. The incidence of GR and GvHD in our CDA cohort was comparable to the recent EBMT report1. Strategies such as aggressive chelation, use of PTIS and perhaps early HCT in the presence of a suitable donor before co-morbidities occur are needed to improve engraftment without increasing risk for toxicities and mortality. Not unexpectedly we observed considerable morbidities in patients who had GR and required a 2nd HCT. Disclosures Pulsipher: Novartis: Honoraria; Bellicum: Honoraria; Jasper: Honoraria; Mesoblast: Honoraria; Miltenyi: Honoraria, Research Funding; Adaptive: Research Funding.
- Published
- 2020
9. Autoimmune Cytopenias Following Allogeneic Hematopoietic Stem Cell Transplant in Pediatric Patients: A Case-Control Cohort Study
- Author
-
Ralph Quinones, Michael R. Verneris, Christopher M. McKinney, Jane Koo, Roger Giller, and Jessica Knight-Perry
- Subjects
Transplantation ,medicine.medical_specialty ,Evans syndrome ,business.industry ,Hematology ,Total body irradiation ,medicine.disease ,Gastroenterology ,Hypogammaglobulinemia ,hemic and lymphatic diseases ,Internal medicine ,Autoimmune neutropenia ,Cohort ,medicine ,Rituximab ,business ,Cohort study ,medicine.drug - Abstract
Introduction Autoimmune cytopenia (AIC) is a rare, but serious complication of allogeneic hematopoietic cell transplantation (HCT), and treatment for post-HCT AIC can have severe short- and long-term consequences. We sought to identify AIC risk factors and evaluate treatment-related late effects, in order to better guide management. Methods We performed a retrospective case-control study of pediatric patients who underwent HCT at Children's Hospital Colorado from June 2005 to March 2019. We compared clinical and transplant-related characteristics, chimerism, immune reconstitution, outcomes and late effects between patients who developed AICs (n=20) and a control group (n=40) matched by primary disease category and donor source. Results The incidence of AIC was 5.6% amongst all patients who received allogeneic HCT in the study timeframe (n=354). Of these, 75% had non-malignant disease (n=15). Thirteen developed autoimmune hemolytic anemia (65%), 5 had immune thrombocytopenia (25%), 1 had Evans syndrome (5%) and 1 had autoimmune neutropenia (5%). Median time to AIC was 219 days (range 97-1205 days). There was no difference between AIC patients and controls in gender, age at HCT, conditioning regimen, serotherapy, total body irradiation (TBI), GVHD prophylaxis, chronic GVHD, or time to neutrophil and platelet recovery. Compared to controls, more AIC patients had ABO mismatch (50% vs. 40%, p=0.07), and a higher proportion of grade I-II acute GVHD (93.9% vs. 50%, p=0.06), but was not statistically significant. Seventeen patients (85%), had >95% donor chimerism immediately prior to development of AIC. Fifteen patients (75%) received steroids as part of first-line therapy for AIC and 17 patients (85%) received rituximab as part of all therapy. Eleven patients (64.7%) received rituximab as part of first-line therapy. Only 25% of patients (n=5) responded to initial therapy. Median time to resolution of AIC was 12.0 months (range 10 days to 90 months). Strikingly, 12 patients (70.6%) are still receiving intravenous immune globulin (IVIG) replacement for hypogammaglobulinemia at least 1-year after HCT at a median time of 597.5 days (range 83-3715 days) from last rituximab dose. Iron overload was more prevalent in AIC patients compared to controls (n=8 vs n=1, p=0.0004, median of 2.3 years after HCT). The overall survival (OS) of the AIC cohort was similar to the control group (85% vs 82.5%). No patients in the AIC cohort died from AIC-related complications. In the AIC cohort, 2 patients died from sepsis and 1 patient died from relapsed disease. Conclusions In this case-control study of pediatric HCT patients, AIC was not associated with mixed chimerism or GVHD. The majority of AIC cases did not respond to first-line therapy and required multiple treatment modalities to achieve a complete response. Late effects from AIC-directed therapies include prolonged hypogammaglobulinemia and iron overload.
- Published
- 2020
10. What Is the Optimal Post-Transplant Cardiac Screening for Transplant Recipients with a Non-Malignant Disease?
- Author
-
Christopher M. McKinney, Michael R. Verneris, Hesham Eissa, Brandon Nuechterlein, and Melissa Croskell
- Subjects
Cardiac function curve ,Transplantation ,medicine.medical_specialty ,business.industry ,Hematology ,Right bundle branch block ,medicine.disease ,Pulmonary hypertension ,Pericardial effusion ,surgical procedures, operative ,Internal medicine ,medicine ,business ,Prospective cohort study ,Aortic valve regurgitation ,Preparative Regimen - Abstract
Introduction There are no published cardiac screening guidelines specific to nonmalignant hematopoietic cell transplant (HCT) recipients. Historically, our program has performed cardiac screening on all transplant recipients, regardless of transplant indication. We performed a quality improvement audit to determine the utility of this practice. Objective Assess the utility of routine cardiac screening post HCT for nonmalignant patients. Methods We performed a retrospective chart review to determine the new pathologies detected by post-HCT ECHO and EKG performed on patients with nonmalignant disorders who underwent HCT at our center from January 1, 2008 – December 31, 2016. Patients were included if they had a nonmalignant disease and an electrocardiogram (EKG) and echocardiogram (ECHO) prior to transplant and at either three months post-transplant, one year and/or yearly thereafter. Results The mean follow-up for the cohort (n=88) was 25 months (range 3-93 mo). Average age was 97 months and transplant indications included: 37% bone marrow failure, 5% metabolic, 22% immune deficiency and 36% other. For these patients, a total of 632 EKGs and 501 ECHOs were reviewed. On average each patient received 2 screening ECHO's and EKGs, post-transplant. Only 1 patient had new cardiac finding on post-transplant cardiac screening. Prior to HCT, this patient, with I cell disease, had right bundle branch block. On post-transplant screening, he was noted to develop mild aortic valve regurgitation, with normal systolic function. Three patients developed new cardiac dysfunction detected on additional screening due to clinical symptoms. One patient developed pericardial effusion and ultimately required the placement of a window. Subsequently, his pericardial effusion resolved, and his cardiac function was normal at last check two years post HCT. Another developed left ventricle enlargement and decreased function secondary to a fungemia. This subsequently resolved following resolution of her infection and cardiac function was normal on her last evaluation. The third died of pulmonary hypertension and decreased ventricular function 22 months post HCT. His Day 100- and 1-year screenings were normal. His dysfunction was detected on additional scans due to clinical symptoms. Conclusion In patients with nonmalignant disorders and a normal pre-transplant cardiac evaluation, the development of post-transplant cardiac complications is rare. This is likely explained by the lack of cardiac toxic medications prior to transplantation or high dose cardiac irradiation during the preparative regimen. Disease specific prospective studies including assessing individual risk factors are needed to guide post-transplant cardiac screening in this widely diverse patient population.
- Published
- 2020
11. Red cell exchange transfusion halts progressive proliferative sickle cell retinopathy in a teenaged patient with hemoglobin SC disease
- Author
-
Jeffrey L. Olson, Christopher M. McKinney, Kelly E. Capocelli, Rachelle Nuss, Daniel R. Ambruso, and Frank S Siringo
- Subjects
Pars plana ,medicine.medical_specialty ,genetic structures ,Hemoglobin SC Disease ,business.industry ,medicine.medical_treatment ,Vitrectomy ,Hematology ,Red cell exchange transfusion ,medicine.disease ,eye diseases ,Surgery ,medicine.anatomical_structure ,Oncology ,Pediatrics, Perinatology and Child Health ,Vitreous hemorrhage ,medicine ,Sickle cell retinopathy ,business ,Retinopathy - Abstract
A male with sickle SC disease presented at age 8 years with proliferative sickle cell retinopathy (PSCR) and bilateral vitreous hemorrhage which spontaneously resolved, then recurred at 13 years of age. Despite conventional therapy with repeated pan-retinal photocoagulation and pars plana vitrectomy, he developed progressive PSCR and recurrent vitreous hemorrhage over the next 30 months. We describe the successful use of chronic red cell exchange transfusion (RCE) to preserve his vision and stabilize the retinopathy.
- Published
- 2015
12. Shared Brain Areas But Not Functional Connections Controlling Movement Timing and Order
- Author
-
Christopher M. Mckinney, Tao Wu, Kenji Kansaku, Guido Nolte, Mark Hallett, and Gaëtan Garraux
- Subjects
Adult ,Male ,Movement ,Context (language use) ,Behavioral/Systems/Cognitive ,Human behavior ,Cerebellum ,medicine ,Humans ,Associative property ,Brain Mapping ,Resting state fMRI ,medicine.diagnostic_test ,General Neuroscience ,Putamen ,Brain ,Motor control ,Cognition ,Middle Aged ,Magnetic Resonance Imaging ,Order (biology) ,Time Perception ,Female ,Psychology ,Functional magnetic resonance imaging ,Neuroscience ,Photic Stimulation ,Psychomotor Performance - Abstract
Virtually every aspect of the enormous repertoire of human behaviors is embedded in a sequential context, but brain mechanisms underlying the adjustment of two fundamental dimensions defining a motor sequence (order of a series of movements and intervals separating them) as a function of a given goal are poorly understood. Using functional magnetic resonance imaging, we demonstrate that, at the neuronal level, these tasks can only be distinguished by differences in functional interactions between associative areas of common activation, which included bilateral subcortico-parieto-frontal regions, and two subcortical structures. Activity in these shared associative areas was preferentially coupled with that in right putamen during manipulation of timing and with that in right posterior cerebellum during manipulation of serial order. This finding is important because it provides evidence for an efficient organization of the brain during cognitive control of motor sequences and supports a recently proposed principle according to which the role of brain regions involved in different behavioral tasks without differential alterations in their measured activity depends on changes in their interactions with other connected areas as a function of the tasks.
- Published
- 2005
13. Red cell exchange transfusion halts progressive proliferative sickle cell retinopathy in a teenaged patient with hemoglobin SC disease
- Author
-
Christopher M, McKinney, Frank, Siringo, Jeffrey L, Olson, Kelly E, Capocelli, Daniel R, Ambruso, and Rachelle, Nuss
- Subjects
Male ,Adolescent ,Retinal Diseases ,Humans ,Hemoglobin SC Disease ,Child ,Erythrocyte Transfusion ,Vitreous Hemorrhage - Abstract
A male with sickle SC disease presented at age 8 years with proliferative sickle cell retinopathy (PSCR) and bilateral vitreous hemorrhage which spontaneously resolved, then recurred at 13 years of age. Despite conventional therapy with repeated pan-retinal photocoagulation and pars plana vitrectomy, he developed progressive PSCR and recurrent vitreous hemorrhage over the next 30 months. We describe the successful use of chronic red cell exchange transfusion (RCE) to preserve his vision and stabilize the retinopathy.
- Published
- 2014
14. Livedoid Dermatitis (Nicolau Syndrome) Following Intra-Articular Glucocorticoid Injection
- Author
-
Nirupma Sharma, Rita S. Jerath, and Christopher M. McKinney
- Subjects
medicine.medical_specialty ,Intra articular ,Rheumatology ,business.industry ,medicine ,Nicolau Syndrome ,Livedoid dermatitis ,business ,medicine.disease ,Dermatology ,Glucocorticoid ,medicine.drug - Published
- 2014
15. Frontal cortex functional connectivity changes during sound categorization
- Author
-
Barry Horwitz, Christopher M. Mckinney, and Fatima T. Husain
- Subjects
Adult ,Male ,Inferior frontal gyrus ,behavioral disciplines and activities ,Functional Laterality ,Superior temporal gyrus ,Discrimination, Psychological ,otorhinolaryngologic diseases ,medicine ,Image Processing, Computer-Assisted ,Temporal dynamics of music and language ,Humans ,Temporal cortex ,Brain Mapping ,medicine.diagnostic_test ,General Neuroscience ,Magnetic Resonance Imaging ,Frontal Lobe ,Oxygen ,Emotional lateralization ,Sound ,Categorization ,Frontal lobe ,Acoustic Stimulation ,Auditory Perception ,Female ,Functional magnetic resonance imaging ,Psychology ,Neuroscience - Abstract
Using functional connectivity analysis of functional magnetic resonance imaging data, we investigated the role of the inferior frontal gyrus in categorization of simple sounds. We found stronger functional connectivity between left inferior frontal gyrus and auditory processing areas in the temporal cortex during categorization of speech (vowels, syllables) and nonspeech (tones, combinations of tones and sweeps) sounds relative to an auditory discrimination task; the hemispheric lateralization varied depending on the speech-like properties of the sounds. Our results attest to the importance of interactions between temporal cortex and left inferior frontal gyrus in sound categorization. Further, we found different functional connectivity patterns between left inferior frontal gyrus and other brain regions implicated in categorization of syllables compared with other stimuli, reflecting the greater facility for categorization of syllables.
- Published
- 2006
16. Complication Rates in Patients with Sickle Cell Disease Living Chronically at Moderate Altitude
- Author
-
Christopher M. McKinney, Claire L. Stokes, and Christopher C. Silliman
- Subjects
medicine.medical_specialty ,Pediatrics ,Hemoglobin SC Disease ,business.industry ,Immunology ,Blood viscosity ,Cell Biology ,Hematology ,medicine.disease ,Rate ratio ,Biochemistry ,Acute chest syndrome ,Sickle cell anemia ,Oxygen tension ,Internal medicine ,Splenic infarction ,medicine ,Cardiology ,business ,Vaso-occlusive crisis - Abstract
Background: The increased risk of acute vaso-occlusive pain crisis and splenic infarction in children with sickle cell disease (SCD) acutely exposed to altitude has been well documented. However, little is known about complication rates in children chronically living at moderate altitude. We hypothesize that children with SCD experience more complications than children with SCD living at sea level. Methods: A retrospective chart review of all patients with sickle cell disease followed at the Children's Hospital Colorado between January 2001 and December 2010 was completed. Patients observed for less than one year were excluded from analysis. Incidence rates for vaso-occlusive crisis (VOC), acute chest syndrome (ACS), splenic sequestration, and stroke were calculated. Rate ratios and 95% confidence intervals were determined comparing to children with SCD from institutions located near sea level. Secondary measures looked at baseline hematologic indices collected at annual comprehensive care visits and percentage of patients with abnormal tricuspid regurgitation jet velocity (TRV). Two-tailed Student's t-tests were used to compare means of continuous variables. Results: 179 children were observed for a total of 1032.37 patient-years with demographics (Table 1). . At moderate altitude, patients with Hgb SS experienced about a 20% higher rate of VOC compared to historic controls with a rate ratio of 1.19 (1.03-1.39) (Table 2). Patients with Hgb SC had almost 3 times the number of admissions for splenic sequestration than those at sea level with a rate ratio of 2.93 (1.05-8.02). Incidence rates for ACS and stroke appeared to have been higher at moderate altitude than sea level, but did not reach statistical significance. There was also no difference in the percentage of patients with abnormal TRV. Baseline lab values were less than the 95%ile except for the hemoglobin of 11.7 for SC patients (Brown et al 1994). Discussion: The oxygen tension at an elevation of 5,280 feet (1,609 m) is 20% lower than at sea level due to the reduction in barometric pressure. Reduced oxygen tension may lead to increased hemoglobin S polymerization and red cell sickling. Hemoglobin SC patients have higher baseline hemoglobins, and their increase in splenic sequestration may be due to increased blood viscosity. Interestingly, the rate of ACS and pulmonary hypertension did not seem to be significantly elevated in our patients living at moderate altitude. This may be due to a lack of statistical power given the small size of this single institution study. Another limitation of this study is the comparison to data from multiple institutions near sea level which does not necessarily control for other possible contributing factors, e.g. climate. Also, VOC events were defined as hospitalizations requiring parenteral opioid administration, which is a stricter definition than used in the sea-level data. Thus, the risk ratio may be underestimated. Nevertheless, the data supports the anecdotal experience that patients living chronically at moderate altitude have increased sickle cell-related complication rates. Table 1 Table 1. Demographics Table 2 Table 2. Complication Incidence Rates 1 -compared to Gill et. al, Blood, 1995 2 - compared to Vichinsky et. al, Blood, 2012 3- compared to Brousse et. al, BJH, 1997 4- compared to Pashankar et. al, Pediatrics, 2007 5- compared to Quinn et. al, Blood, 2008 Disclosures No relevant conflicts of interest to declare.
- Published
- 2014
17. fMRI language task panel improves determination of language dominance
- Author
-
Phillip L. Pearl, Bonnie C. Sachs, William D. Gaillard, Lyn Balsamo, L. G. Vezina, Benjamin Xu, P. H. Papero, C. Frattali, Steven L. Weinstein, Joan A. Conry, Susumu Sato, William H. Theodore, and Christopher M. Mckinney
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Audiology ,behavioral disciplines and activities ,Temporal lobe ,Developmental psychology ,Task (project management) ,Epilepsy ,Predictive Value of Tests ,Preoperative Care ,medicine ,Verbal fluency test ,Humans ,Child ,Dominance, Cerebral ,Language ,Cerebral Cortex ,Brain Mapping ,Language Tests ,Verbal Behavior ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Temporal Lobe ,Inter-rater reliability ,Dominance (ethology) ,Reading comprehension ,Cerebrovascular Circulation ,Laterality ,Speech Perception ,Female ,Neurology (clinical) ,Psychology ,psychological phenomena and processes - Abstract
Background: fMRI language tasks reliably identify language areas in presurgical epilepsy patients, but activation using single paradigms may disagree with the intracarotid amobarbital test (IAT). Objective: To determine whether a panel of fMRI tasks targeting different aspects of language processing increases accuracy in determining hemisphere language dominance. Methods: Twenty-six patients age 12 to 56 years, predominantly with temporal lobe epilepsy, were studied using whole-brain 1.5 T fMRI (echo planar imaging, blood oxygenation level–dependent) with three task categories using a block design: verbal fluency, reading comprehension, and auditory comprehension. fMRI t maps were visually rated at three thresholds. All patients had assessment of language lateralization by IAT. Results: fMRI showed left dominance in 21 patients, right dominance in 2, and bilateral activation in 2; raters disagreed over a left vs right bilateral rating in 1 patient. There was full agreement between IAT and fMRI in 21 of 25 patients (IAT failed in 1). In three instances of partial disparity with IAT, the fMRI panel showed consistent findings across raters. Agreement between raters was excellent (partial disagreement in only one patient); the panel of tasks was superior to any single task for interrater agreement (Cramer V 0.93 [range 0.91 to 1.0] vs 0.72 [range 0.60 to 0.86]). Conclusions: A panel of fMRI language paradigms may be more accurate for evaluating partial epilepsy patients than a single task. A panel of tasks reduces the likelihood of nondiagnostic findings, improves interrater reliability, and helps confirm language laterality.
- Published
- 2004
18. Developmental aspects of language processing: fMRI of verbal fluency in children and adults
- Author
-
Ben Xu, Joseph R. Whitnah, K.E. Hunter, Zaaira Ahmad, S.H. Braniecki, William D. Gaillard, C.B. Grandin, Bonnie C. Sachs, Lyn Balsamo, Christopher M. Mckinney, and Jeffrey R. Petrella
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Audiology ,Left inferior frontal gyrus ,Brain mapping ,behavioral disciplines and activities ,Functional Laterality ,Developmental psychology ,Region of interest ,Left middle frontal gyrus ,medicine ,Image Processing, Computer-Assisted ,Verbal fluency test ,Humans ,Radiology, Nuclear Medicine and imaging ,Child ,Research Articles ,Language ,Brain Mapping ,Radiological and Ultrasound Technology ,Age Factors ,Semantic fluency ,Brain ,Magnetic Resonance Imaging ,Neurology ,El Niño ,Laterality ,Visual Perception ,Female ,Neurology (clinical) ,Anatomy ,Psychology - Abstract
We examined developmental differences, in location and extent of fMRI language activation maps, between adults and children while performing a semantic fluency task. We studied 29 adults and 16 children with echo planar imaging BOLD fMRI at 1.5 T using covert semantic verbal fluency (generation of words to categories compared to rest) using a block design. Post task testing was administered to assess performance. Individual data were analyzed with an a priori region of interest approach from t maps (t = 4) and asymmetry indices (AI). Group studies were analyzed using SPM 99 (Wellcome, UK; fixed effect, corrected P < 0.0001). We found no significant differences in location or laterality of activation between adults and children for a semantic verbal fluency task. Adults activated more pixels than children in left inferior frontal gyrus and left middle frontal gyrus, but AIs were the similar across ages (r(2) < 0.09). Extent or laterality of activation was not affected by performance (r(2) < 0.15). The brain areas that process semantic verbal fluency are similar in children and adults. The laterality of activation does not change appreciably with age and appears to be strongly lateralized by age 7 years. Hum. Brain Mapping 18:176–185, 2003. © 2003 Wiley‐Liss, Inc. Published 2003 Wiley‐Liss, Inc.
- Published
- 2003
19. Changes In Cell-Derived Plasma Microparticles During The Acute Chest Syndrome In Children With Sickle Cell Disease
- Author
-
Marguerite R. Kelher, Christopher C. Silliman, and Christopher M McKinney
- Subjects
medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Systemic inflammation ,Biochemistry ,Gastroenterology ,Sickle cell anemia ,Pathophysiology ,Acute chest syndrome ,Hemoglobinopathy ,Internal medicine ,medicine ,Platelet ,medicine.symptom ,business ,Prospective cohort study ,Whole blood - Abstract
Introduction Microparticles (MP) are small (less than 1 µm), membrane-derived extracellular vesicles produced following cellular activation or apoptosis. They have been implicated as causative in a wide variety of pro-inflammatory diseases. Sickle cell disease is a hemoglobinopathy characterized by chronic hemolysis and systemic inflammation which can be complicated by vaso-occlusive pain crises (VOC) or the acute chest syndrome (ACS). Increasingly there is evidence that microparticles may play an important role in the pathophysiology of sickle cell disease. We hypothesize that plasma microparticles are elevated during ACS compared to VOC and baseline (resting). Methods Whole blood was obtained under an approved consent from the Colorado Multiple Institution Review Board at the University of Colorado Denver, from three subjects with homozygous sickle cell disease (ages 4-18) at three distinct time points: baseline (resting) at routine clinic visits and upon hospitalization for VOC and ACS. The samples underwent differential centrifugation: plasma was isolated (5,000xg for 7 min at RT) and then cell free supernatant was separated (12,500xg for 6 min at 4°C). MPs were isolated by centrifugation at 17,000xg for 60 minutes at 4°C, and the MP pellet was resuspended in an equal volume of 1.25% human serum albumin. The samples were incubated with CD41 (PE)-, CD45 (PerCP-Cy5)-, and CD235 (FITC)-antibodies that are specific for MPs derived from platelets, leukocytes, and erythrocytes, respectively, and analyzed by flow cytometry. Statistics were performed using ANOVA with post-hoc Newman-Keuls test. Results The amount of leukocyte-derived MP (WBC) measured during ACS was significantly higher (almost two-fold) than levels measured during baseline (resting) (p < 0.05), but not VOC. The erythrocyte (RBC) MP levels were also significantly elevated during ACS, compared to resting and VOC (p Discussion Microparticles may play a significant role in the pathophysiology of ACS in sickle cell disease. Leukocyte-derived MPs are elevated in ACS at higher levels than baseline. This likely reflects the important role of white blood cells (WBCs) in systemic inflammation and the importance of WBC-endothelial interactions in ACS. While platelet- and erythrocyte-derived MPs may be involved in ACS, a larger sample size will be needed to detect this effect. In addition, while hospitalized, two patients who had a similar magnitude increase in WBC MPs during VOC eventually progressed to ACS; thus, serial MP measurements could potentially serve as a biomarker to identify patients at risk for imminent development of ACS. Further prospective studies with larger sample sizes will be needed for validation. Future directions of study should also evaluate the role of endothelial-derived MPs and the role of ICAM-1. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2013
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.