Image formation in vibro-acoustography with depth-of-field effects.

We study the image formation of vibro-acoustography systems based on a concave sector array transducer taking into account depth-of-field effects. The system point-spread function (PSF) is defined in terms of the acoustic emission of a point-target in response to the dynamic radiation stress of ultrasound. The PSF on the focal plane and the axis of the transducer are presented. To extend the obtained PSF to the 3D-space, we assume it is a separable function in the axial direction and the focal plane of the transducer. In this model, an image is formed through the 3D convolution of the PSF with an object function. Experimental vibro-acoustography images of a breast phantom with lesion-like inclusions were compared with simulated images. Results show that the experimental images are in good agreement with the proposed model.     

Effect of sequential administration of an opioid and cholecystokinin on gallbladder ejection fraction: brief communication.

This study was undertaken to test the effect of sequential administration of an opioid and intravenous cholecystokinin (CCK) on gallbladder ejection fraction. METHODS: Forty-nine patients who had received an opioid underwent quantitative cholescintigraphy with octapeptide of CCK (CCK-8). Gallbladder ejection fraction and CCK-8-induced paradoxical filling were calculated. RESULTS: In the basal state, more of the hepatic bile entered the gallbladder (67%) than the small intestine (33%). After CCK-8 infusion, gallbladder ejection fraction was low in 37 (76%) of 49 patients and normal in 12 (24%). All 5 types of opioids lowered ejection fraction. CCK-induced paradoxical filling of the gallbladder was noted in 7 patients, but only one showed paradoxical filling of greater than 20% and none had a normal gallbladder ejection fraction. The lowering effect of opioids on gallbladder ejection fraction may last as long as 18 h after intake. CONCLUSION: CCK-8 produced a normal gallbladder ejection fraction in 24% of patients who had received an opioid and thus could exclude both acute and chronic cholecystitis during a single hepatobiliary study.     

An update on the overnight dexamethasone suppression test for the diagnosis of Cushing's syndrome: limitations in patients with mild and/or episodic hypercortisolism.

The overnight one-mg dexamethasone suppression test has been used for many years to screen for Cushing's syndrome. This test has usually been evaluated in controls versus patients with severe hypercortisolism. Under these conditions, the overnight dexamethasone suppression test has been reported to have high sensitivity and specificity. The objective of this study was to determine the sensitivity of the one mg overnight dexamethasone suppression test in patients with mild and/or periodic Cushing's syndrome. Therefore, an overnight dexamethasone suppression test was performed in 17 consecutive patients presenting to an endocrinology clinic with signs and symptoms of hypercortisolemia who were later proven to have Cushing's syndrome. The majority of patients were found to have both mild and periodic hypercortisolism. One mg of dexamethasone was given at midnight and a plasma cortisol was measured by radioimmunoassay at 08:00 the following morning. Using a cut-off for a morning cortisol following overnight dexamethasone of > 5 microg/dL, only three of 17 patients failed to suppress to a value less than this cut-off (sensitivity 18 %). A cut-off of > 2 microg/dL gave similar sensitivity. Even with a stringent cut-off point of > 1.8 microg/dL, only seven of 17 patients failed to suppress to a value less than this cut-off point (sensitivity of 41 %). These results demonstrate that the great majority of patients with mild and/or periodic Cushing's syndrome suppress to overnight dexamethasone. Since patients with mild and/or periodic Cushing's syndrome are the patients in whom the identification of hypercortisolism is difficult, our results from this relatively small study suggest that this test should no longer be used to exclude these patients from further workup for Cushing's syndrome.     

Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

Isolated Donor Specific Alloantibody-Mediated Rejection after ABO Compatible Liver Transplantation

Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d.     

Costimulation and Autoimmune Diabetes in BB Rats

Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55–120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb) with different functional activities completely prevented diabetes in BBDP rats. Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes resistant BB (BBDR) rats are disease-free, but >95% of them develop diabetes after treatment with polyinosinic-polycytidylic acid and an mAb that depletes Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes, whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no effect. In contrast, blockade of the CD134-CD134L pathway was highly effective for preventing autoimmune recurrence against syngeneic islet grafts in diabetic BBDR hosts. Blockade of the CD40-CD154 pathway was also effective, but less so. These data suggest that the effectiveness of costimulation blockade in the treatment of type 1 diabetes is dependent on both the costimulatory pathway targeted and the mechanism of induction, stage, intensity and duration of the pathogenic process.     

Refractory Ascites After Liver Transplantation: An Analysis of 1058 Liver Transplant Patients at a Single Center

A retrospective study of 1058 liver transplant recipients was performed to determine: (i) the incidence, etiology, timing, clinical features and treatment of refractory ascites (RA), (ii) risk factors for RA development, (iii) predictors of RA disappearance, (iv) predictors of survival following RA and (v) the impact of RA on patient survival. Sixty-two patients (5.9%) developed RA and its disappearance occurred in 27/62 cases. Patients having hepatitis C virus (HCV) had a significantly higher hazard rate of developing RA (p < 0.00001). No other baseline characteristic was associated with RA. Cox stepwise regression analysis of the hazard rate of RA disappearance found two significant factors: HCV recurrence as the reason for developing RA implied a poorer outcome (p = 0.006), whereas an unknown reason implied a favorable outcome (p = 0.02). In addition, survival following RA was significantly poorer among patients having bacterial peritonitis or HCV recurrence. Finally, the mortality rate was significantly (nearly 8.6 times) higher in patients following RA development while it was ongoing (p < 0.00001); however, if the RA disappeared, then the additional risk of death also disappeared. This study illustrates the importance of developing an optimal treatment strategy to (i) effectively treat RA if it develops and (ii) prevent hepatitis C recurrence.     

Case Report: Second case of a successful pregnancy in maternal isovaleric acidaemia

Summary: A female patient with isovaleric acidaemia had a successful outcome from pregnancy.