Pediatric spontaneous tension pneumothorax in Langerhans cell histiocytosis.

Langerhans cell histiocytosis is a rare hematologic disorder caused by the proliferation of specialized dendritic cells. Pulmonary manifestations occur in 20% to 50% of multisystem disease, but isolated pulmonary disease is rare. Spontaneous pneumothorax occurs in up to 10% of pediatric pulmonary cases.

An experimental study of factors associated with driver frustration and overtaking intentions.

This study examined directly the impact of various factors associated with driving on 'A-class' roads in the United Kingdom (specifically length of platoon, proportion of heavy goods vehicles (HGVs), speed and opportunities for overtaking) on self-reported frustration and overtaking intentions. The impact of situational variables (being under time pressure, and time behind a slower moving platoon) were also examined, as was the association between frustration and self-reported overtaking intentions. 183 members of the public from the areas around Perth and Inverness, Scotland took part in the study.

Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia.

Background: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults.

Methods: We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL.

Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB₂ receptor agonists for pain management.

SAR studies on a series of thiophene amide derivatives provided CB(2) receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A representative compound with selectivity for CB(2) over CB(1) effectively produced analgesia in behavioral models of neuropathic, inflammatory, and postsurgical pain.

Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity.

Several 3-acylindoles with high affinity for the CB(2) cannabinoid receptor and selectivity over the CB(1) receptor have been prepared. A variety of 3-acyl substituents were investigated, and the tetramethylcyclopropyl group was found to lead to high affinity CB(2) agonists (5, 16). Substitution at the N1-indole position was then examined.

A study of the adhesion between dental cement and dentin using a nondestructive acoustic microscopy approach.

Objectives: The goal of the present study was to investigate the potential for acoustic microscopy techniques to characterize the cement-dentin interface in restored teeth.

Methods: Special flat-parallel specimens and whole extracted teeth with restorations were scanned using a high-frequency (50 MHz) focused ultrasonic transducer. Visual acoustic images (B- and C-scans) of the cement-dentin interface were obtained nondestructively, analyzed and compared with optical images taken after the samples were cut along the scanning axis.

Characterization of human cannabinoid CB2 receptor coupled to chimeric Galpha(qi5) and Galpha(qo5) proteins.

Cannabinoid CB(2) receptors may couple to a variety of G proteins and intracellular effector systems to regulate physiological and pathophysiological processes involved in inflammatory and neuropathic pain. In this study, the coupling of cannabinoid hCB(2) receptors to Galpha(qo5) and Galpha(qi5) proteins was studied and compared by investigating the pharmacological properties of HEK-293 cells co-expressing cannabinoid hCB(2) with chimeric Galpha(qo5) (HEK-hCB(2)-G(qo5)) or Galpha(qi5) (HEK-hCB(2)-G(qi5)). Both cell lines were found to be amendable for measuring cannabinoid CB(2) receptor agonist evoked Ca(2+) mobilization in a high-throughput manner.

Characterization of a cannabinoid CB2 receptor-selective agonist, A-836339 [2,2,3,3-tetramethyl-cyclopropanecarboxylic acid [3-(2-methoxy-ethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide], using in vitro pharmacological assays, in vivo pain models, and pharmacological magnetic resonance imaging.

Studies demonstrating the antihyperalgesic and antiallodynic effects of cannabinoid CB(2) receptor activation have been largely derived from the use of receptor-selective ligands. Here, we report the identification of A-836339 [2,2,3,3-tetramethyl-cyclopropanecarboxylic acid [3-(2-methoxy-ethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide], a potent and selective CB(2) agonist as characterized in in vitro pharmacological assays and in in vivo models of pain and central nervous system (CNS) behavior models. In radioligand binding assays, A-836339 displays high affinities at CB(2) receptors and selectivity over CB(1) receptors in both human and rat.

Unrelated cord blood transplantation in children with idiopathic severe aplastic anemia.

Early results of unrelated cord blood transplantation (UCBT) for severe aplastic anemia (SAA) were poor with a high rate of engraftment failure. This was attributed to the combination of lower graft cell dose and intact host immune system. We performed UCBT in nine children (median age 9 years) with refractory SAA using increasingly immunosuppressive preparative regimens.

Structure-activity relationship studies on N'-aryl carbohydrazide P2X7 antagonists.

N'-aryl acyl hydrazides were identified as P2X7 receptor antagonists. Structure-activity relationship (SAR) studies evaluated functional activity by monitoring calcium flux inhibition in cell lines expressing recombinant human and rat P2X7 receptors. Selected analogs were assayed in vitro for their capacity to inhibit release of cytokine IL-1beta.

Indol-3-yl-tetramethylcyclopropyl ketones: effects of indole ring substitution on CB2 cannabinoid receptor activity.

A series of potent indol-3-yl-tetramethylcyclopropyl ketones have been prepared as CB 2 cannabinoid receptor ligands. Two unsubstituted indoles ( 5, 32) were the starting points for an investigation of the effect of indole ring substitutions on CB 2 and CB 1 binding affinities and activity in a CB 2 in vitro functional assay. Indole ring substitutions had varying effects on CB 2 and CB 1 binding, but were generally detrimental to agonist activity.

Synthesis and in vitro activity of 1-(2,3-dichlorophenyl)-N-(pyridin-3-ylmethyl)-1H-1,2,4-triazol-5-amine and 4-(2,3-dichlorophenyl)-N-(pyridin-3-ylmethyl)-4H-1,2,4-triazol-3-amine P2X7 antagonists.

A novel series of aminotriazole-based P2X(7) antagonists was synthesized, and their structure-activity relationships (SAR) were investigated for activity at both human and rat P2X(7) receptors. Most compounds showed greater potency at the human receptor although several analogs were discovered with potent activity (pIC(50) > or = 7.5) at both human and rat P2X(7).

In vitro and in vivo characterization of A-796260: a selective cannabinoid CB2 receptor agonist exhibiting analgesic activity in rodent pain models.

Background And Purpose: Selective cannabinoid CB2 receptor agonists have demonstrated analgesic activity across multiple preclinical pain models. AM1241 is an indole derivative that exhibits high affinity and selectivity for the CB2 binding site and broad spectrum analgesic activity in rodent models, but is not an antagonist of CB2 in vitro functional assays. Additionally, its analgesic effects are mu-opioid receptor-dependent.

Novel and potent 3-(2,3-dichlorophenyl)-4-(benzyl)-4H-1,2,4-triazole P2X7 antagonists.

Structure-activity relationship (SAR) studies were conducted around early tetrazole-based leads 3 and 4. Replacements for the tetrazole core were investigated and the pendant benzyl substitution was reoptimized with a triazole isostere. Triazole-based P2X(7) antagonists were identified with similar potency to the lead compound 4 but with improved physiochemical properties.

In vitro pharmacological characterization of AM1241: a protean agonist at the cannabinoid CB2 receptor?

Background And Purpose: The CB2 receptor has been proposed as a novel target for the treatment of pain, and CB2 receptor agonists defined in in vitro assays have demonstrated analgesic activity in animal models. Based on its in vivo analgesic efficacy, AM1241 has been classified as a CB2-selective agonist. However, in vitro characterization of AM1241 in functional assays has not been reported.

Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists.

1-Benzyl-5-aryltetrazoles were discovered to be novel antagonists for the P2X(7) receptor. Structure-activity relationship (SAR) studies were conducted around both the benzyl and phenyl moieties. In addition, the importance of the regiochemical substitution on the tetrazole was examined.

Preclinical profiling and safety studies of ABT-769: a compound with potential for broad-spectrum antiepileptic activity.

Purpose: The objective of this study was to characterize the antiseizure and safety profiles of ABT-769 [(R)-N-(2 amino-2-oxoethyl)spiro[2,5]octane-1-carboxamide].

Methods: ABT-769 was tested for protection against maximal electroshock and pentylenetetrazol-induced seizures in the mouse and for suppression of electrically kindled amygdala seizures and spontaneous absence-like seizures in the rat. The central nervous system safety profile was evaluated by using tests of motor coordination and inhibitory avoidance.

ABT-963 [2-(3,4-difluoro-phenyl)-4-(3-hydroxy-3-methyl-butoxy)-5-(4-methanesulfonyl-phenyl)-2H-pyridazin-3-one], a highly potent and selective disubstituted pyridazinone cyclooxgenase-2 inhibitor.

Nonsteriodal anti-inflammatory drugs (NSAIDs) are efficacious for the treatment of pain associated with inflammatory disease. Clinical experience with marketed selective cyclooxygenase-2 (COX-2) inhibitors (celecoxib, rofecoxib, and valdecoxib) has confirmed the utility of these agents in the treatment of inflammatory pain with an improved gastrointestinal safety profile relative to NSAID comparators. These COX-2 inhibitors belong to the same structural class.

Identification and characterization of novel antagonists of the CCR3 receptor.

Eotaxin, an inducer of eosinophil migration and activation, exerts its activity by binding to CCR3, the C-C chemokine receptor 3. An inhibitor of the eotaxin-CCR3 binding interaction may have potential as an anti-inflammatory drug for treatment of asthma, parasitic infections, and allergic disorders. A radioligand binding assay was developed using HEK cells transfected with CCR3, with (125)I eotaxin as the ligand.

Effects of plate location and selection on the stability of midshaft clavicle osteotomies: a biomechanical study.

Operative fixation of midshaft clavicle fractures is controversial with few biomechanical data to assist surgical decision making. The purpose of this 2-phase biomechanical investigation is to report on the effects of plate location and selection on the stability of midshaft clavicle fractures. Thirty matched pairs of human adult formalin-fixed clavicles were used.

Unrelated cord blood transplant experience by the pediatric blood and marrow transplant consortium.

Cord blood (CB) has emerged as a potential source of hematopoietic stem cells for patients who are in need of hematopoietic stem cell transplant (HSCT). The authors analyzed the Pediatric Blood and Marrow Transplant Consortium's (PBMTC) data of consecutive unrelated CB transplants performed during the initial 2 years of using placental blood grafts. From January 1995 to December 1996 PBMTC performed a total of 44 unrelated CB transplant for a variety of diseases consisting of acute leukemias (n = 29), congenital conditions (n = 9), and bone marrow failure (n = 6).

Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group.

Untreated patients with Hurler syndrome (MPSIH) experience progressive neurologic deterioration and early death. Allogeneic bone marrow transplantation (BMT) ameliorates or halts this course. The Storage Disease Collaborative Study Group was formed to evaluate the effectiveness and toxicity of BMT.

Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome.

Long-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bone marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.

The effects of California Proposition 187 on ophthalmology clinic utilization at an inner-city urban hospital.

Purpose: To determine the effect on ophthalmology clinic utilization at a major public inner-city hospital of California Proposition 187 and the debate surrounding its passage. Proposition 187 was a statewide referendum passed by 63% of the electorate in the November 1994 election that would restrict social services to undocumented immigrants and require providers to report them to immigration authorities.

Methods: The ophthalmology clinic volume at the Los Angeles County/ University of Southern California Medical Center was analyzed from October 1 to December 31, 1993 and 1994.