STUDIES ON THE PATHOGENESIS OF FEVER : XV. THE PRODUCTION OF ENDOGENOUS PYROGEN BY PERITONEAL MACROPHAGES

Macrophages from oil-induced peritoneal exudates in rabbits produce endogenous pyrogen when first activated by incubation in 4 hr exudate fluid and then stimulated by incubation in potassium-free isotonic sodium chloride solution. The failure of earlier investigators to obtain pyrogen from macrophages is explained, and the relevance of macrophage pyrogen to fevers of agranulocytosis and other diseases, in which mononuclear rather than granulocytic exudates predominate, is discussed.     

Role of 16-multidetector computed tomography in the assessment of coronary artery stenoses: A prospective study of consecutive patients

BACKGROUND: Recent studies have demonstrated a high sensitivity (S) of 16-multidetector computed tomography (16-MDCT) for the detection of significant coronary artery stenoses. Whether these results are applicable to clinical practice is unclear. Therefore, the aim of the present study was to compare 16-MDCT angiography with conventional coronary angiography (CCA) for the detection of significant coronary artery stenoses in a consecutive series of patients. METHOD: A total of 93 consecutive patients (mean [+/- SD] age 59+/-9 years), in whom CCA was performed for stable angina pectoris, underwent 16-MDCT angiography (16x0.75 mm, table feed 6.5 mm/s, rotation time 0.42 s; Sensation 16, Siemens Medical Solutions, Germany) the day before performing CCA. Patients with diabetes mellitus, serum creatinine level higher than 132.6 mumol/L and/or acute coronary syndromes were excluded. Two observers blinded to CCA results evaluated MDCT angiograms according to standard criteria. Segment-based (13 segments per patient) and patient-based (at least one stenosis greater than 50% lumen diameter reduction) analyses were performed. RESULTS: A total of 1209 segments were analyzed. Of these segments, 173 (14%) were excluded due to poor image quality or massive calcification. In 86 segments, CCA revealed significant coronary artery stenosis (greater than 50% diameter reduction). However, 16-MDCT detected only 47 of these, resulting in a S of 55% and a specificity (SP) of 97% (positive predictive value 64%; negative predictive value 96%). On a patient-based analysis, the S increased to 89%, whereas the SP still remained high (87%). CONCLUSION: In this relatively large consecutive cohort, S for the detection of significant coronary artery stenoses was moderate on a segment-based analysis but increased on a patient-based analysis using 16-MDCT. In contrast, SP was high in both analyses, supporting the use of 16-MDCT for the exclusion of significant coronary artery stenoses. Further improvement of spatial and temporal resolution in MDCT technology may lead to a lower exclusion rate and higher S.     

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

We describe that galectin-1 (gal-1) is a receptor for the angiogenesis inhibitor anginex, and that the protein is crucial for tumor angiogenesis. gal-1 is overexpressed in endothelial cells of different human tumors. Expression knockdown in cultured endothelial cells inhibits cell proliferation and migration. The importance of gal-1 in angiogenesis is illustrated in the zebrafish model, where expression knockdown results in impaired vascular guidance and growth of dysfunctional vessels. The role of gal-1 in tumor angiogenesis is demonstrated in gal-1-null mice, in which tumor growth is markedly impaired because of insufficient tumor angiogenesis. Furthermore, tumor growth in gal-1-null mice no longer responds to antiangiogenesis treatment by anginex. Thus, gal-1 regulates tumor angiogenesis and is a target for angiostatic cancer therapy.     

Targeted deletion of Nm23/nucleoside diphosphate kinase A and B reveals their requirement for definitive erythropoiesis in the mouse embryo

The ubiquitously expressed nucleoside diphosphate kinases (Nm23/NDPK/Awd) are a large family of multifunctional enzymes implicated in nucleic acid metabolism and in normal and abnormal development. Here, we describe the generation and characterization of NDPK A‐ and B‐deficient (Nme1^?/?/Nme2^?/?) mice in which >95% of the enzyme activity is eliminated. These mice are undersized, die perinatally, and exhibit a spectrum of hematological phenotypes including severe anemia, impaired maturation of erythrocytes, and abnormal hematopoiesis in the liver and bone marrow. Flow cytometric analysis of developing Nme1^?/?/Nme2^?/? erythroid cells indicated that the major iron transport receptor molecule TfR1 is attenuated concomitant with a reduction of intracellular iron, suggesting that TfR1 is a downstream target of NDPKs and that reduced iron in Nme1^?/?/Nme2^?/? erythroblasts is inhibiting their development. We conclude that Nm23/NDPKs play critical roles in definitive erythroid development. Our novel mouse model also links erythropoiesis and nucleotide metabolism. Developmental Dynamics 238:775–787, 2009. © 2009 Wiley‐Liss, Inc.     

Interhospital transfer of blunt multiply injured patients to a level 1 trauma center does not adversely affect outcome

Background

Stops at nontrauma centers for severely injured patients are thought to increase deaths and costs, potentially because of unnecessary imaging and indecisive/delayed care of traumatic brain injuries (TBIs).

Methods

We studied 754 consecutive blunt trauma patients with an Injury Severity Score greater than 20 with an emphasis on 212 patients who received care at other sites en route to our level 1 trauma center.

Results

Referred patients were older, more often women, and had more severe TBI (all P < .05). After correction for age, sex, and injury pattern, there was no difference in the type of TBI, Glasgow Coma Scale (GCS) upon arrival at the trauma center, or overall mortality between referred and directly admitted patients. GCS at the outside institution did not influence promptness of transfer.

Conclusions

Interhospital transfer does not affect the outcome of blunt trauma patients. However, the unnecessarily prolonged stay of low GCS patients in hospitals lacking neurosurgical care is inappropriate.     

Identifying viable theoretical frameworks with essential parameters for real-time and real world alcohol craving research: a systematic review of craving models

Background: Substance use is known to be episodic, dynamic, complex, and highly influenced by the environment, therefore a situational and momentary focus to alcohol craving research is appropriate. Current advances in mobile and wearable technology provide novel opportunities for craving research. However, the lack of consensus within craving theory impedes the identification and prioritization of parameters to be monitored. The aim of this study is to critically review current craving models in order to determine viable theoretical frameworks of alcohol craving and its essential parameters.

Methods: Eighteen models of craving were reviewed by applying a literature search with a five-step strategy that accounted for the momentary nature of craving and included a snowballing search and a key term extraction algorithm. Based on this review, multiple decision criteria were defined upon which to evaluate the models.

Results: Six models for alcohol craving were supported by sufficient empirical research to be eligible. The inferences drawn on these six models resulted in three decision criteria: the model should (1) incorporate negative affect as a predictor of relapse; (2) explain that dependent drinkers have a higher attentional bias towards alcohol cues than nondependent drinkers; (3) incorporate increased risk of relapse with heightened stress levels.

Conclusions: The affective processing model of negative reinforcement, the cognitive processing model, the incentive sensitization theory of addiction and the theory of neural opponent motivation are classified as viable theoretical frameworks, resulting in negative affect and stress as relevant parameters to include in real-time craving monitoring research.