Factors affecting mortality and morbidity in patients with abdominal gunshot wounds

Risk factors that may independently predict mortality and morbidity in patients with abdominal gunshot wounds have not been fully elucidated. We prospectively studied the effects of 12 potential risk factors on mortality and morbidity in 82 patients with abdominal gunshot wounds who required laparotomy. Univariate analysis of these factors revealed that shock on admission, presence of penetrating colon injury and number of intra-abdominal organs injured (NOI)>2 were associated with greater than threefold increased incidence of death (p<0.05). Penetrating abdominal trauma index (PATI) score>15 was associated with twentyfold increased incidence of death (P<0.0001). Multivariate analysis showed that only PATI (P=0.001), number of postoperative complications per patient (N(comp)) (P=0.023) and presence of shock on admission (P=0. 028) were independently significant in predicting mortality. PATI was the only risk factor that independently predicted the development of postoperative infectious complications and N(comp) (P<0.0001). The type of gun used was not a significant risk factor (P>0.05). The 15 (18.3%) non-survivors were significantly older than survivors (P=0.02), had longer operations (P=0.004) and their NOI, PATI and N(comp) were significantly higher (P<0.001). The uniformly prolonged injury to surgery time in all patients contributed to the high incidence of infectious complications (62.2%) and mortality. PATI score was the most important factor found to be independently associated with mortality and morbidity in our subset of patients with prolonged injury to surgery time and high rate of colon injury.     

Variable compensation technique for digital radiography of the chest

The authors describe a new technique, variable compensation (VC) radiography, for digital radiography of the chest. It permits retrospective adjustment of image display while maintaining improved mediastinal signal-to-noise ratio (S/N) from aggressive x-ray equalization. A fraction of a logarithmic image representing the profile of the beam intensity incident on the patient is subtracted from a logarithmic equalized image. VC images of a chest phantom were generated with various weightings of the beam-profile image. Edge artifacts were substantially reduced with a weighting of greater than 0.5 and eliminated with a weighting of 1.0. The S/N properties of VC images were measured with a series of plastic squares placed over various regions of the chest phantom. The S/N of the squares in the dense sub-diaphragm were improved twofold compared with the S/N on unequalized radiographs, whereas the S/N in the lung was reduced by 30%. Studies of a volunteer revealed the ability to render images with aggressive equalization (for improved mediastinal visualization) and images with the appearance of traditional chest radiographs.     

Induction of tumor-specific T cell response by cognating tumor cells with foreign antigen-primed Th cells

Sufficient CD4+ T cell help is very important in generating specific cytotoxic T cell responses. The inadequate activation of tumor-specific Th cells leads to failure of antitumor immunity. In general, each individual consists of some primed Th cells responding to certain antigens. If these tumor non-specific pre-primed Th cells can provide sufficient help, the generation of tumor-specific T cells may be enhanced. In the present study, we tested this hypothesis by cognating and reactivating pre-primed ovalbumin (OVA)-specific Th cells with OVA- pulsed tumor cells which could simultaneously present both OVA and tumor-associated antigen on the same cell. We clearly demonstrated that immunization of OVA-sensitized mice with OVA-pulsed P388 cells, but not unpulsed P388 cells, led to the induction of P388-specific cytotoxicity and tumor resistance. Both CD4+ and CD8+ tumor-specific cytotoxic T cells were detected in vitro, but only CD8+ T cells played the major effector role in preventing the growth of challenged tumor in vivo. Taken together, our study demonstrated that the immunogenicity of tumor cells can be enhanced effectively by cognating pre-primed foreign antigen-specific Th cells with tumor cells. These findings have potential implications in developing methods to control tumor growth.      

Hepatic metastasis detection: comparison of three CT contrast enhancement methods

A prospective, blinded comparison of three methods of hepatic contrast enhancement in computed tomography (CT) was conducted in 15 patients with colorectal carcinoma metastatic to the liver. Arterial portography (AP-CT) was performed with injection of contrast material into the superior mesenteric artery during CT. Delayed scanning (DS-CT) was performed 4 hours after intravascular administration of contrast material (mean dose, 280 mL). CT with an ethiodized oil emulsion (EOE-CT) was performed 1 hour after slow intravenous infusion of the emulsion. All patients underwent laparotomy following imaging studies. A lesion-by-lesion analysis of 56 metastases showed no significant differences in sensitivity (AP-CT, 77%; DS-CT, 83%; EOE-CT, 82%), but the false-positive rate for AP-CT was significantly higher than that for DS-CT (P less than .001) or EOE-CT (P less than .01). False-positive rates for EOE-CT and DS-CT were not significantly different. The predictive value of a positive test was 63% for AP-CT, 90% for DS-CT, and 81% for EOE-CT. AP-CT does not appear to be clinically useful for detection of hepatic metastases because of the high false-positive rate. No difference could be demonstrated between DS-CT and EOE-CT. DS-CT is a valuable method for hepatic contrast enhancement.     

Amebic liver abscess: diagnosis and treatment evaluation with MR imaging

Magnetic resonance images were obtained before and after treatment in 17 patients with 29 amebic liver abscesses. Pretreatment T1-weighted images showed a sharply circumscribed, heterogeneous, low-signal-intensity mass, devoid of normal hepatic tissue and corresponding to the abscess cavity as measured sonographically. T2-weighted images showed the abscess cavity as a hyperintense region and also showed a larger region of hyperintensity extending from the cavity margins to the liver surface, corresponding to edematous but morphologically normal liver tissue. After treatment, the abscess cavity became homogeneously hypointense on T1-weighted images, corresponding to liquefaction of the abscess center. With successful treatment, concentric rings corresponding to (a) an inner margin of inflamed granulation tissue, (b) bands of type I collagen, and (c) the outer margin of atrophic and/or mildly inflamed liver tissue became prominent on T1- and T2-weighted images. T2-weighted images showed rapid resolution of the perifocal hepatic edema.     

Increased microvessel density in involved organs from patients with HTLV-I associated adult T cell leukemia lymphoma

Adult T-cell leukemia-lymphoma (ATLL) is a rapidly progressive lymphoproliferative disorder secondary to infection with the human T cell lymphotropic virus type I (HTLV-I). The role of angiogenesis in the development and prognosis of many hematologic malignancies is established. We have previously shown that ATLL derived cells secrete high levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), induce endothelial tube formation in vitro and establish functional gap junction-mediated communication with endothelial cells. We also demonstrated that plasma from ATLL and tropical spastic paraparesis/HTLV-I associated myelopathy patients exhibit very high levels of VEGF and b-FGF. Recently, we showed that treatment with the combination of zidovudine and interferon alpha reduced both HTLV-I proviral load and importantly VEGF plasma levels suggesting a potential anti-angiogenic effect of this therapy. In this report, we evaluated microvessel density (MVD) in involved organs from 20 patients with ATLL, as compared to normal organs from matched controls. We show evidence of significantly increased MVD in all tested involved organs from ATLL patients, suggesting that angiogenesis plays an important role in the development or organ invasion of ATLL, and could represent a potentially interesting target for anti-angiogenic therapy of ATLL.     

��-Arrestin 1 and 2 stabilize the angiotensin II type I receptor in distinct high-affinity conformations

BACKGROUND AND PURPOSE

The angiotensin II type 1 (AT₁) receptor belongs to family A of 7 transmembrane (7TM) receptors. The receptor has important roles in the cardiovascular system and is commonly used as a drug target in cardiovascular diseases. Interaction of 7TM receptors with G proteins or β-arrestins often induces higher binding affinity for agonists. Here, we examined interactions between AT_1A receptors and β-arrestins to look for differences between the AT_1A receptor interaction with β-arrestin1 and β-arrestin2.

EXPERIMENTAL APPROACH

Ligand-induced interaction between AT_1A receptors and β-arrestins was measured by Bioluminescence Resonance Energy Transfer 2. AT_1A-β-arrestin1 and AT_1A-β-arrestin2 fusion proteins were cloned and tested for differences using immunocytochemistry, inositol phosphate hydrolysis and competition radioligand binding.

KEY RESULTS

Bioluminescence Resonance Energy Transfer 2 analysis showed that β-arrestin1 and 2 were recruited to AT_1A receptors with similar ligand potencies and efficacies. The AT_1A-β-arrestin fusion proteins showed attenuated G protein signalling and increased agonist binding affinity, while antagonist affinity was unchanged. Importantly, larger agonist affinity shifts were observed for AT_1A-β-arrestin2 than for AT_1A-β-arrestin1.

CONCLUSION AND IMPLICATIONS

β-Arrestin1 and 2 are recruited to AT_1A receptors with similar ligand pharmacology and stabilize AT_1A receptors in distinct high-affinity conformations. However, β-arrestin2 induces a receptor conformation with a higher agonist-binding affinity than β-arrestin1. Thus, this study demonstrates that β-arrestins interact with AT_1A receptors in different ways and suggest that AT₁ receptor biased agonists with the ability to recruit either of the β-arrestins selectively, would be possible to design.