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Biomedical subjects

James Black

Publications and source records attributed to James Black.

11 recordsLinked to original sources
PubMed2005

Models developed by three techniques did not achieve acceptable prediction of binary trauma outcomes.

BACKGROUND AND OBJECTIVES: To develop prediction models for outcomes following trauma that met prespecified performance criteria. To compare three methods of developing prediction models: logistic regression, classification trees, and artificial neural networks. METHODS: Models were developed using a 1996-2001 dataset from a major trauma center in Victoria, Australia. Developed models were subjected to external validation using the first year of data collection, 2001-2002, from a state-wide trauma registry for Victoria. Different authors developed models for each method. All authors were blinded to the validation dataset when developing models. RESULTS: Prediction models were developed for an intensive care unit stay following trauma (prevalence 23%) using information collected at the scene of the injury. None of the three methods gave a model that satisfied the performance criteria of sensitivity >80%, positive predictive value >50% in the validation dataset. Prediction models were also developed for death (prevalence 2.9%) using hospital-collected information. The performance criteria of sensitivity >95%, specificity >20% in the validation dataset were not satisfied by any model. CONCLUSION: No statistical method of model development was optimal. Prespecified performance criteria provide useful guides to interpreting the performance of developed models.

Adult↗
PubMed2005

Serum parathyroid hormone-related peptide is associated with systemic inflammation and adverse prognosis in gastroesophageal carcinoma.

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) is a tumor-derived circulating factor that has been associated with hypercalcemia of malignancy. The role of PTHrP as a prognostic indicator remains unclear. Studies suggest that it may function as a growth factor; and, recently, the ability of PTHrP to induce cytokine expression has been described. PTHrP also has been proposed as a procachectic factor. In this study, the authors investigated the prognostic value of PTHrP in patients who had gastroesophageal carcinoma without hypercalcemia and determined whether PTHrP was associated with systemic inflammation and adverse nutritional status. METHODS: Patients were recruited at the time of diagnosis. Serum was collected for determination of c-terminal fragment PTHrP (cPTHrP) levels (by radioimmunoassay) and calcium levels as well as levels of serum cytokines and acute-phase proteins (with an enzyme-linked immunosorbent assay). Nutritional assessment of patients was undertaken at the same time as serum collection. Patients underwent routine staging, and survival duration was recorded. RESULTS: One hundred fifty-one patients with esophagogastric carcinoma were recruited. Six of 151 patients (4.0%) patients were hypercalcemic, and 26 patients (17.2%) had elevated serum cPTHrP levels. There was no association between the cPTHrP level and either serum calcium concentrations (P = 0.72) or adverse nutritional status. Elevated cPTHrP, however, was associated with significantly higher serum levels of soluble tumor necrosis factor receptor (P = 0.008) and with significantly lower levels of transferrin (P = 0.009) and albumin (P = 0.02). There was also a weak association with C-related protein levels (P = 0.06). Elevated cPTHrP levels also were associated with an adverse prognosis, as determined by reduced survival duration, on univariate analysis (P = 0.038), but not on multivariate analysis (P = 0.15). CONCLUSIONS: Elevated serum cPTHrP levels were present in approximately 17% of patients with gastroesophageal carcinoma in the absence of hypercalcemia and was associated with markers of systemic inflammation and with an adverse prognosis.

Adenocarcinoma↗
PubMed2005

Pim-1 ligand-bound structures reveal the mechanism of serine/threonine kinase inhibition by LY294002.

Pim-1 is an oncogene-encoded serine/threonine kinase primarily expressed in hematopoietic and germ cell lines. Pim-1 kinase was originally identified in Maloney murine leukemia virus-induced T-cell lymphomas and is associated with multiple cellular functions such as proliferation, survival, differentiation, apoptosis, and tumorigenesis (Wang, Z., Bhattacharya, N., Weaver, M., Petersen, K., Meyer, M., Gapter, L., and Magnuson, N. S. (2001) J. Vet. Sci. 2, 167-179). The crystal structures of Pim-1 complexed with staurosporine and adenosine were determined. Although a typical two-domain serine/threonine protein kinase fold is observed, the inter-domain hinge region is unusual in both sequence and conformation; a two-residue insertion causes the hinge to bulge away from the ATP-binding pocket, and a proline residue in the hinge removes a conserved main chain hydrogen bond donor. Without this hydrogen bond, van der Waals interactions with the hinge serve to position the ligand. The hinge region of Pim-1 resembles that of phosphatidylinositol 3-kinase more closely than it does other protein kinases. Although the phosphatidylinositol 3-kinase inhibitor LY294002 also inhibits Pim-1, the structure of the LY294002.Pim-1 complex reveals a new binding mode that may be general for Ser/Thr kinases.

Adenosine↗
PubMed2004

The structural basis for autoinhibition of FLT3 by the juxtamembrane domain.

FLT3 is a type III receptor tyrosine kinase that is thought to play a key role in hematopoiesis. Certain classes of FLT3 mutations cause constitutively activated forms of the receptor that are found in significant numbers of patients with acute myelogenous leukemia (AML). The mutations occur either in the activation loop, for example, as point mutations of Asp835 or as internal tandem duplication (ITD) sequences in the juxtamembrane (JM) domain. To further understand the nature of FLT3 autoinhibition and regulation, we have determined the crystal structure of the autoinhibited form of FLT3. This structure shows the autoinhibitory conformation of a complete JM domain in this class of receptor tyrosine kinases. The detailed inhibitory mechanism of the JM domain is revealed, which is likely utilized by other members of type III receptor tyrosine kinases.

Amino Acid Sequence↗
PubMedDate not supplied

Psychotropic discontinuation symptoms: a case of withdrawal neuroleptic malignant syndrome.

INTRODUCTION: Although recent publications have focused on discontinuation symptoms of antidepressant medications, most classes of psychotropic drugs have been reported to have withdrawal symptoms. In light of the increased rate of psychotropic prescribing by primary care physicians, it is important for all physicians to be aware of psychotropic withdrawal symptoms. CASE REPORT: We report on a patient who developed symptoms consistent with neuroleptic malignant syndrome after abrupt discontinuation of a variety of psychotropic medications. METHODS: A MEDLINE search including both articles and letters to the editor was performed to identify symptoms reported in association with the discontinuation of psychotropic medications.

Adult↗
PubMedDate not supplied

Integrated decision-making in response to weapons of mass destruction incidents: development and initial evaluation of a course for healthcare professionals.

INTRODUCTION: Standardized, validated training programs for teaching administrative decision-making to healthcare professionals responding to weapons of mass destruction (WMD) incidents have not been available. Therefore, a multidisciplinary team designed, developed, and offered a four-day, functional exercise, competency-based course at a national training center. OBJECTIVE: This report provides a description of the development and initial evaluation of the course in changing participants' perceptions of their capabilities to respond to WMD events. METHODS: Course participants were healthcare professionals, including physicians, nurses, emergency medical services administrators, hospital administrators, and public health officials. Each course included three modified tabletop and/or real-time functional exercises. A total of 441 participants attended one of the eight course offerings between March and August 2003. An intervention group only, pre-post design was used to evaluate change in perceived capabilities related to administrative decision-making for WMD incidents. Paired evaluation data were available on 339 participants (81.9%). Self-ratings for each of 21 capability statements were compared before and after the course. A 19-item total scale score for each participant was calculated from the pre-course and post-course evaluations. Paired t-tests on pre- and post-course total scores were conducted separately for each course. RESULTS: There was consistent improvement in self-rated capabilities after course completion for all 21 capability statements. Paired t-tests of pre- and post-course total scale scores indicated a significant increase in mean ratings for each course (all p < 0.001). CONCLUSION: The tabletop/real-time-exercise format was effective in increasing healthcare administrators' self-rated capabilities related to WMD disaster management and response. Integrating the competencies into training interventions designed for a specific target audience and deploying them into an interactive learning environment allowed the competency-based training objectives to be accomplished.

Bioterrorism↗
PubMedDate not supplied

Gallbladder carcinoma: findings at MR imaging with MR cholangiopancreatography.

PURPOSE: To describe magnetic resonance (MR) imaging and MR cholangiopancreatography (MRCP) findings in gallbladder carcinoma, and to correlate these findings with available surgical and biopsy information. METHODS: Preoperative MR images (T1-weighted spin-echo, T2-weighted fast spin-echo, single shot fast spin-echo, and dynamic gadolinium-enhanced gradient echo) in 34 patients with gallbladder carcinoma were retrospectively reviewed for appearance of the primary neoplasm and for demonstration of hepatic, peritoneal, duodenal, and nodal involvement. Imaging findings were then compared with surgical findings (n = 19 patients) and histologic findings (n = 15 patients). RESULTS: Gallbladder carcinoma manifested at MR imaging as focal gallbladder wall thickening with an eccentric mass in 76% (26/34) of cases. The most common types of regional spread demonstrated were direct liver invasion in 91% (31/34), lymphadenopathy in 76% (26/34), and biliary tract invasion in 62% (21/34). Sensitivity for direct hepatic invasion was 100%, and was 92% for lymph node metastasis. CONCLUSION: MRI and MRCP can provide information relevant to preoperative staging of gallbladder carcinoma.

Gallbladder↗
PubMedDate not supplied

Enhancing parent-child interaction during foster care visits: experimental assessment of an intervention.

Mothers of young children recently placed in foster care participated in an intervention to enhance parent-child interaction during visits. The mothers all reported substantial loss and trauma histories. Immediately prior to the visits, the mothers were coached on strategies for separating from their children at the visit's end. The mothers displayed more behavioral strategies for supporting their children when the visit was over, but were less engaged with their children during the leave-taking sequence and displayed fewer ways of maintaining the child's involvement in mother-child interaction during leave-taking than those in a comparison group. This article discusses consideration of parents' trauma history in designing interventions to enhance parent-child interaction.

Adolescent↗