Intercellular adhesion molecule-1 inhibition attenuates neurologic and hepatic damage after resuscitation in mice

BACKGROUND: Cardiac arrest and cardiopulmonary resuscitation may result in multiorgan damage after global hypoxia due to neutrophil recruitment. Patients display all signs of a systemic inflammatory response syndrome. Reducing neutrophil recruitment may thus preserve organ function. METHODS: Mice were subjected to cardiac arrest and resuscitation. CD18/CD11b expression on circulating neutrophils was assessed by flow cytometry. Intercellular adhesion molecule-1 expression was analyzed by Western blot and immunofluorescence. Neutrophil recruitment was quantified by immunohistochemistry. Neurologic function was assessed by a balance test. For liver and kidney function, plasma alanine aminotransferase activity and creatinine concentrations were determined. To reduce neutrophil recruitment, mice received 100 microg anti-intercellular adhesion molecule-1 antibody intraperitoneally. RESULTS: Resuscitation led to severe hypoxia, acidosis, and hypercarbia. Adhesion molecule expression and neutrophil recruitment were increased in the liver, kidney, and brain. Neurologic performance was impaired 24 h after cardiac arrest. Creatinine and alanine aminotransferase concentrations were significantly increased. Immunoneutralization of intercellular adhesion molecule-1 attenuated neutrophil influx in the liver along with alanine aminotransferase activity, whereas creatinine concentrations and neutrophil influx in the kidney remained unchanged. Neurologic function was improved in the treatment group. CONCLUSIONS: Global hypoxia induces activation of the endothelium in the brain, liver, and kidney. The resulting damage to the brain and liver are due to infiltration of neutrophils, whereas kidney damage is not, because reduction of neutrophil recruitment after cardiopulmonary resuscitation improves recovery of neurologic and hepatic but not renal function. Inhibition of intercellular adhesion molecule-1 after global hypoxia may be beneficial in patients experiencing cardiac arrest and resuscitation.     

PAX5/IGH rearrangement is a recurrent finding in a subset of aggressive B-NHL with complex chromosomal rearrangements

We present an extensive characterization of 10 B-cell lymphomas with a t(9;14)(p13;q32). The presence of the PAX5/IGH gene rearrangement was demonstrated by fluorescence in situ hybridization (FISH) using a validated probe set, whereas complex karyotypic changes were reassessed by multiplex-FISH (M-FISH). Pathologic and clinical review revealed the presence of this rearrangement in 4 histiocyte-rich, T-cell-rich B-cell lymphomas (HRTR-BCLs) and 2 posttransplantation diffuse large B-cell lymphomas (PTLD-DLBCLs). In contrast to initial observations describing this translocation in lymphoplasmacytic lymphoma (LPL) and LPL-derived large B-cell lymphoma, our data showed a wide morphologic and clinical spectrum associated with the PAX5/IGH rearrangement, pointing to an association between this aberration and a subset of de novo DLBCLs presenting with advanced disease and adverse prognosis. In addition, the recurrent incidence of this rearrangement in both HRTR-BCL (4 cases) and PTLD-DLBCL (2 cases) was previously unrecognized and is intriguing.     

Medication patterns for attention-deficit/hyperactivity disorder and comorbid psychiatric conditions in a low-income population

The aims of this study were two-fold: (1) to describe the patterns of comorbid psychiatric diagnosis and psychotropic drug therapy for children enrolled in a Medicaid-managed care program and diagnosed with attention-deficit/hyperactivity disorder (ADHD) in 2000 and (2) to examine child and provider characteristics associated with psychotropic medication patterns for this population. Multivariate logistic regression models were used to examine correlates of stimulant and seven nonstimulant psychotropic medication classes (alpha-agonists, mood stabilizer/anticonvulsant, antianxiety, standard antipsychotic, atypical antipsychotic, and tricyclic antidepressant (TCA)/other antidepressant and selective serotonin reuptake inhibitor (SSRI) antidepressant). With the exception of conduct disorders (odds ratio, 1.22; 95% confidence interval, 1.06-1.40), comorbid disorders had a significant protective effect (odds ratio less than 1) on dispensing stimulants. After adjusting for covariates, stimulant dispensing was strongly correlated with the interactions of geographic region with race/ethnicity and provider type. Children residing in the upstate New York region had an approximately ten-fold greater chance of being dispensed a stimulant compared to similar children in New York City. Utilizing a mental health provider increased the chance of being dispensed a stimulant by factor of two for children from New York City of any race/ethnicity group. Models predicting nonstimulant drug dispensing were distinct from the stimulant model. After adjusting for covariates, nonstimulant psychotropic medication dispensing was correlated with clinical factors, including comorbid disorder category and use of a mental health provider, as well as notable sociodemographic factors. Complex psychotropic medication and comorbid psychiatric disorder patterns were evident for this low-income population of children with ADHD. The roles of clinical, patient, and provider factors need to be better understood to explain these patterns of stimulant and nonstimulant psychotropic medications dispensed.     

Initial experience with an endoscopic radial artery harvesting technique

OBJECTIVE: The purpose of the study was to investigate the feasibility of an endoscopic radial artery harvesting technique to improve esthetic results and possibly reduce the incidence of neurologic complications observed with the open method. METHODS: Between July 1, 2002, and October 1, 2003, a total of 54 patients underwent endoscopic radial artery harvesting at our institution. Standard endoscopic equipment and a Harmonic Scalpel (Ethicon Endo-Surgery, Inc, Cincinnati, Ohio) were used. Mean age of the patients was 63 +/- 8.1 years, and 16% were female. All patients underwent a preoperative Allen test and duplex ultrasonography to demonstrate adequate ulnar collateral flow. The nondominant arm was used for radial artery harvesting. Mean clinical follow-up was 13 +/- 4.6 months. RESULTS: The artery was harvested through a 3-cm incision at the wrist and was divided at the elbow either through a small counterincision (n = 16) or endoscopically with the use of clips, Endoloop, and endoscopic scissors (n = 38). Mean harvest time was 42.2 +/- 16.9 minutes but decreased from 85 minutes for the first cases to 25 minutes for the last 5 cases. Mean harvested length was 19.6 +/- 1.7 cm. Harvesting complications included 1 conversion, 2 postoperative hematomas, 1 injury, 8 endoscopically controlled bleedings, and 15 cases of at least some superficial radial nerve paresthesia at 6 weeks (clinically relevant in 4 cases). Selective postoperative angiography revealed 1 occluded graft and 1 stenotic graft requiring percutaneous transluminal coronary angioplasty of the native vessel. Eighty-seven percent of the patients were enthusiastic about this new procedure. CONCLUSIONS: Endoscopic radial artery harvesting is a feasible procedure that requires a definite learning curve. Although nerve paresthesias were not completely eliminated in our experience, the technique provided ample patient satisfaction. Further clinical follow-up is required to determine long-term patency rates.     

Prenatal ultrasound and magnetic resonance imaging in fetal varicella syndrome: correlation with pathology findings

OBJECTIVES: To assess the diagnostic value of prenatal magnetic resonance imaging (MRI) in addition to prenatal ultrasound in a case of fetal varicella syndrome. METHODS: Comparison of prenatal ultrasound and MRI features obtained at 26 and 32 weeks, respectively, with neonatal imaging (ultrasound, MRI and CT) and macroscopic and microscopic pathology findings in a fatal case of varicella embryopathy. RESULTS: Prenatal ultrasound correlated fairly well with neonatal imaging and pathology findings. Most lesions of thoracic, abdominal and retroperitoneal viscera, limb involvement and even dermatologic features were apparent on ultrasonography. Involvement of the CNS, including cerebellar hypoplasia, was not apparent on ultrasound examination, but was clearly demonstrated by prenatal MRI. CONCLUSION: If maternal seroconversion for the varicella-zoster virus is suspected, combining prenatal ultrasound and magnetic resonance imaging may document the extent of tissue damage in fetal varicella syndrome to a larger extent than has been reported until now and therefore contribute to due counselling following maternal varicella exposure.