Biomedical subjects

Gregory Hale

Publications and source records attributed to Gregory Hale.

8 recordsLinked to original sources

PubMed2006

Exploration in outbred mice covaries with general learning abilities irrespective of stress reactivity, emotionality, and physical attributes.

Across multiple learning tasks (that place different sensory, motor, and information processing demands on the animals), we have found that the performance of mice is commonly regulated by a single factor ("general learning") that accounts for 30-40% of the variance across individuals and tasks. Furthermore, individuals' general learning abilities were highly correlated with their propensity to engage in exploration in an open field, a behavior that is potentially stress-inducing. This relationship between exploration in the open field and general learning abilities suggests the possibility that variations in stress sensitivity/responsivity or related emotional responses might directly influence individuals' general learning abilities. Here, the relationship of sensory/motor skills and stress sensitivity/emotionality to animals' general learning abilities were assessed. Outbred (CD-1) mice were tested in a battery of six learning tasks as well as 21 tests of exploratory behavior, sensory/motor function and fitness, emotionality, and stress reactivity. The performances of individual mice were correlated across six learning tasks, and the performance measures of all learning tasks loaded heavily on a single factor (principal component analysis), accounting for 32% of the variability between animals and tasks. Open field exploration and seven additional exploratory behaviors (including those exhibited in an elevated plus maze) also loaded heavily on this same factor, although general activity, sensory/motor responses, physical characteristics, and direct measures of fear did not. In a separate experiment, serum corticosterone levels of mice were elevated in response to a mild environmental stressor (confinement on an elevated platform). Stress-induced corticosterone levels were correlated with behavioral fear responses, but were unsystematically related to individuals' propensity for exploration. In total, these results suggest that although general learning abilities are strongly related to individuals' propensity for exploration, this relationship is not attributable to variations in sensory/motor function or the individuals' physiological or behavioral sensitivity to conditions that promote stress or fear.

Animals↗

PubMed2006

Allogeneic graft-versus-hepatoblastoma effect.

Although the survival rate for pediatric patients with hepatoblastoma has improved, prognosis is still poor when the disease is unresectable and refractory to chemotherapy. Therefore, novel approaches are warranted. Herein, we describe a patient with recurrent metastatic hepatoblastoma who received a non-myeloablative hematopoietic stem cell transplantation from an HLA-matched unrelated donor. After withdrawal of immunosuppressant and establishment of full donor T-cell engraftment, the tumor regressed and serum alpha-fetoprotein level decreased in concurrence with the onset of graft-versus-host disease (GVHD). Her disease recurred when GVHD resolved. This patient's clinical course provides evidence for the probable existence of allogeneic graft-versus-hepatoblastoma effect.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Outcome of hematopoietic stem cell transplantation for pediatric patients with therapy-related acute myeloid leukemia or myelodysplastic syndrome.

BACKGROUND: Therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) carry a poor prognosis. We analyzed the results of allogeneic HSCT in 38 children to determine which factors, if any, affected outcome. PROCEDURE: The effects of demographic, donor, and disease-related factors were analyzed to determine their effects on overall and disease-free survival (OS, DFS), relapse, and non-relapse mortality (NRM). RESULTS: OS and DFS for t-AML and t-MDS were similar. Three-year OS and EFS were the same (15.4 +/- 5.8%) and the 3-year NRM was 59.6 +/- 8.4%. The 1-year cumulative risk of grade III-IV acute graft-versus-host disease (GVHD) and relapse were 23.7 +/- 7.0% and 18.7 +/- 6.5%, respectively. The percentage of pre-transplant bone marrow (BM) blasts was positively associated with relapse (P = 0.05), while the percentage of BM blasts at diagnosis of therapy-related disease tended to associate with NRM (P = 0.07). Alternative donor and matched sibling donor grafts had similar outcomes. NRM was higher among patients who did not develop acute GVHD as compared to those with grade 1-2 acute GVHD (69.2 +/- 14.2% vs. +/- 12.7%, respectively), while NRM was 100% in patients with grade III-IV acute GVHD (P = 0.007). CONCLUSIONS: The percentage of BM blasts is associated with relapse in these disorders. High rates of NRM negatively impact the outcome of allogeneic HSCT for children with t-AML and t-MDS. Future studies should focus on reducing NRM.

Adolescent↗

PubMed2006

Diagnostic challenge in recurrent skin rash after autologous bone marrow transplantation.

Engraftment syndrome, autologous graft-versus-host disease (GVHD), and infection after autologous hematopoietic cell transplantation can have similar clinical presentations. Here, we describe a patient with refractory Ewing sarcoma who had recurrent skin rash after autologous hematopoietic cell transplantation. Although the rash was diagnosed as GVHD histologically, this case illustrates the diagnostic dilemma of distinguishing engraftment syndrome, autologous GVHD, or concomitant viral infection. Because therapy for these entities is different, distinguishing them is important. Establishment of diagnostic criteria and understanding of the pathophysiology of these entities may lead to better management and to improved therapy of refractory cancer.

Adolescent↗

PubMed2005

Variations in working memory capacity predict individual differences in general learning abilities among genetically diverse mice.

Up to 50% of an individuals' performance across a wide variety of distinct cognitive tests can be accounted for by a single factor (i.e., "general intelligence"). Despite its ubiquity, the processes or mechanisms regulating this factor are a matter of considerable debate. Although it has been hypothesized that working memory may impact cognitive performance across various domains, tests have been inconclusive due to the difficulty in isolating working memory from its overlapping operations, such as verbal ability. We address this problem using genetically diverse mice, which exhibit a trait analogous to general intelligence. The general cognitive abilities of CD-1 mice were found to covary with individuals' working memory capacity, but not with variations in long-term retention. These results provide evidence that independent of verbal abilities, variations in working memory are associated with general cognitive abilities, and further, suggest a conservation across species of mechanisms and/or processes that regulate cognitive abilities.

Animals↗

PubMed2005

Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy.

PURPOSE: To describe clinical features, therapeutic approaches, and prognostic factors in pediatric patients with atypical teratoid/rhabdoid tumors (ATRT) treated at St Jude Children's Research Hospital (SJCRH). PATIENTS AND METHODS: Primary tumor samples from patients diagnosed with ATRT at SJCRH between July 1984 and June 2003 were identified. Pathology review included histologic, immunohistochemical analysis, and fluorescence in situ hybridization for SMARCB1 (also known as hSNF5/INI1) deletion. Clinical records of patients with pathologic confirmation of ATRT were reviewed. RESULTS: Thirty-seven patients were diagnosed with ATRT at SJCRH during the 19-year study interval. Six patients were excluded from this clinical review based on pathologic or clinical criteria. Of the remaining 31 patients, 22 were younger than 3 years. Posterior fossa primary lesions and metastatic disease at diagnosis were more common in younger patients with ATRT. All patients underwent surgical resection; 30 received subsequent chemotherapy. The majority of patients aged 3 years or older received postoperative craniospinal radiation. Two-year event-free (EFS) and overall survival (OS) of children aged 3 years or older (EFS, 78% + 14%; OS, 89% +/- 11%) were significantly better than those for younger patients (EFS, 11% +/- 6%; OS, 17% +/- 8%); EFS, P = .009 and OS, P = .0001. No other clinical characteristics were predictive of survival. Three of four patients 3 years or older with progressive disease were successfully rescued with ifosfamide, carboplatin, and etoposide therapy. CONCLUSION: Children presenting with ATRT before the age of 3 years have a dismal prognosis. ATRT presenting in older patients can be cured using a combination of radiation and high-dose alkylating therapy. Older patients with relapsed ATRT can have salvage treatment using ICE chemotherapy.

Central Nervous System Neoplasms↗

PubMed2003

Etiology and outcome of graft failure in pediatric hematopoietic stem cell transplant recipients.

PURPOSE: To determine the incidence, etiology and outcome of graft failure in pediatric allogeneic bone marrow transplant (BMT) recipients. PATIENTS AND METHODS: Patients with primary or secondary graft failure were identified by database review. A retrospective chart review was performed. Etiologic factors were identified and assessed for statistical significance. RESULTS: 309 children underwent allogeneic BMT during the time interval studied. Four cases of primary graft failure and 7 cases of secondary graft failure occurred. Nonmalignant diagnosis, lower total nucleated cell (TNC) dose, and conditioning without total body irradiation were associated with a higher incidence of graft failure. Donor source, donor/recipient CMV status, CD34+ cell dose, and alloimmunization were not associated with graft failure. CONCLUSIONS: Graft failure is a relatively uncommon occurrence in pediatric patients. Autologous reinfusion may allow time to prepare the patient for a second transplant and decrease complications associated with aplasia. More immunosuppressive conditioning regimens may decrease the incidence of graft failure, particularly in patients with non-malignant diseases or those with lower stem cell doses. More frequent monitoring of chimerism by VNTR analysis may detect late graft failure earlier and allow for more rapid intervention.

Bone Marrow Transplantation↗

PubMed2002

Human leucocyte antigen alloimmunization after bone marrow transplantation: an association with chronic myelogenous leukaemia.

Platelet refractoriness due to human leucocyte antigen (HLA) alloimmunization is a significant risk to allogeneic bone marrow transplant recipients. To identify factors contributing to this risk, we reviewed the records of 317 consecutive, paediatric, allogeneic bone marrow transplant recipients at a single institution. The 6-year estimated cumulative incidence of platelet refractoriness due to HLA alloimmunization was 2.6% +/- 0.9%. The incidence among patients with chronic myelogenous leukaemia (CML) 12.5% +/- 5.3% was significantly greater than that of other patients (1.1% +/- 0.6%, P < 0.001). Graft rejection (P = 0.003) and the number of platelet transfusions during the first 90 d after bone marrow transplantation (BMT) (P = 0.0025) were also significantly associated with alloimmunization. The association with CML and with graft rejection was not seen among patients alloimmunized before transplantation. Eight patients developed alloimmunization, of whom three had mismatched grafts and four had unrelated grafts. Alloantibody specificities, identified in seven patients, were unrelated to host or graft major histocompatibility complex (MHC). Host recognition of alloantigens in transfused blood products, not graft-host recognition, therefore seems predominantly responsible for the alloimmunization. These results show that paediatric CML patients have a significantly increased risk of platelet refractoriness due to HLA alloimmunization after BMT. Identifying the mechanism for the increased alloimmunization risk may assist in the development of therapies to prevent platelet refractoriness.

Adolescent↗