Temporal Changes in Innate and Adaptive Immunity During Sepsis as Determined by ELISpot.

Background: The inability to evaluate host immunity in a rapid quantitative manner in patients with sepsis has severely hampered development of novel immune therapies. The ELISpot assay is a functional bioassay that measures the number of cytokine-secreting cells and the relative amount of cytokine produced at the single-cell level. A key advantage of ELISpot is its excellent dynamic range enabling a more precise quantifiable assessment of host immunity. Herein, we tested the hypothesis on whether the ELISpot assay can detect dynamic changes in both innate and adaptive immunity as they often occur during sepsis. We also tested whether ELISpot could detect the effect of immune drug therapies to modulate innate and adaptive immunity. Methods: Mice were made septic using sublethal cecal ligation and puncture (CLP). Blood and spleens were harvested serially and ex vivo IFN-γ and TNF-α production were compared by ELISpot and ELISA. The capability of ELISpot to detect changes in innate and adaptive immunity due to in vivo immune therapy with dexamethasone, IL-7, and arginine was also evaluated. Results: ELISpot confirmed a decreased innate and adaptive immunity responsiveness during sepsis progression. More importantly, ELISpot was also able to detect changes in adaptive and innate immunity in response to immune-modulatory reagents, for example dexamethasone, arginine, and IL-7 in a readily quantifiable manner, as predicted by the reagents known mechanisms of action. ELISpot and ELISA results tended to parallel one another although some differences were noted. Conclusion: ELISpot offers a unique capability to assess the functional status of both adaptive and innate immunity over time. The results presented herein demonstrate that ELISpot can also be used to detect and follow the in vivo effects of drugs to ameliorate sepsis-induced immune dysfunction. This capability would be a major advance in guiding new immune therapies in sepsis.

Children with atopic histories exhibit impaired lipopolysaccharide-induced Toll-like receptor-4 signalling in peripheral monocytes.

BACKGROUND: The hygiene hypothesis states that early exposure to bacterial products such as lipopolysaccharide (LPS) may be protective against the development of allergic diseases. Whether atopic disease affects the ability of immune cells to respond to LPS is unclear. Our laboratory has demonstrated previously that children express high levels of Toll-like receptor (TLR)-4 on CD4(+) cells in nasal mucosa. OBJECTIVE: To determine if children with a history of allergic disease have impaired responses to LPS on circulating CD4(+) leucocytes. METHODS: Peripheral blood mononuclear cells from children (aged 2-18) and adults with or without a history of atopic conditions were cultured with/without IL-4 or LPS for up to 24 h. Expression of surface TLR-4, CD14, CD4, CD3, as well as of intracellular phosphorylated (p42/p44) ERK and p38 mitogen-activated protein kinase (MAPK) were assessed by flow cytometry. RESULTS: A history of atopy in children was associated with impaired LPS-induced TLR-4-dependent phosphorylation of (p42/44) ERK and p38 MAPK by CD4(+) monocytes. Decreased LPS signalling was reproduced by pre-incubation of control cells with recombinant IL-4. LPS stimulation also decreased TLR-4 expression on monocytes from children without atopic histories but not from atopic subjects. CD4(+) T lymphocytes showed limited LPS responsiveness, regardless of atopic status. In contrast with non-atopic children, TLR-4 expression on monocytes of children with atopic histories decreased as a function of age. CONCLUSIONS: This study provides evidence for defective LPS recognition on circulating CD4(+) leucocytes of subjects with atopic histories compared with those from non-atopic children. CD4(+) TLR4(+) monocytes from children with atopic histories failed to phosphorylate MAPKs. Our results suggest that a history of atopic disease is associated with impaired TLR-4-mediated innate immune function compared with non-atopic children.

Detection of caval obstruction by magnetic resonance imaging after intraatrial repair of transposition of the great arteries.

Vena caval obstruction may cause significant morbidity after intraatrial repair of transposition of the great arteries (TGA). Two noninvasive methods of diagnosing vena caval obstruction were compared with cardiac catheterization. Echocardiographically gated magnetic resonance imaging (MRI) and echocardiographic evaluation (2-dimensional saline contrast echocardiography and pulsed Doppler flow measurement) were performed on 15 patients 0.7 to 13.5 years after intraatrial repair of TGA (8 Mustard, 7 Senning). At catheterization, complete superior vena cava or partial caval obstruction (gradient greater than 5 mm Hg from cava to systemic venous atrium) was present in 7 of 15 patients. Superior vena cava obstruction was directly visualized by MRI in both patients with catheterization-proved complete superior vena cava occlusion. A dilated azygous/hemiazygous venous complex (greater than or equal to 5 mm cross-sectional diameter) was seen by MRI in 5 of 7 patients with complex or partial vena caval obstruction and in no patient without vena caval obstruction. MRI showed superior vena caval dilatation (ratio of superior vena caval diameter to aortic diameter greater than 1.45) in 3 of 5 patients with partial vena caval obstruction and in 0 of 8 without vena caval obstruction. Direct visualization of narrowing within the atrium was unreliable for any MRI plane because of the 3-dimensional nature of the intraatrial baffle. Two-dimensional saline contrast echocardiography, successfully performed in 12 of 15 patients, detected complete superior vena caval obstruction only in the 2 patients with catheterization-proved complete superior vena cava occlusion. Contrast echocardiography failed to identify any of the 5 patients with partial vena caval obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

The "aortic nipple" as a sign of impending superior vena caval syndrome.

The development of dilatation of the left superior intercostal vein ("aortic nipple") on chest radiographic studies can be used as a clue to impending superior vena caval syndrome. Two cases are described in which detection of an "aortic nipple" on chest roentgenograms predated the clinical syndrome by seven to ten weeks. Since superior vena caval syndrome is a medical emergency, recognition of signs such as this which may significantly predate the "full-blown" syndrome have far-reaching implications in the care of patients.

Hydrostatic pulmonary edema in sheep. Effects of bronchial artery embolization on the plain chest radiograph.

RATIONALE AND OBJECTIVES: The bronchial circulation may influence pulmonary edema. This study evaluates possible effects of bronchoesophageal artery embolization on the plain film manifestations of hydrostatic pulmonary edema in sheep. METHODS: Anteroposterior and lateral chest radiographs were obtained during the induction of pulmonary edema both before and after embolization of the bronchoesophageal artery in six adult sheep. Interstitial lines and perivascular, segmental bronchial, proximal bronchial, carinal, tracheal, and parenchymal edema were evaluated. RESULTS: Only parenchymal edema was graded consistently. Though edema increased with left atrial pressure before embolization (P < .001), there was no similar change afterward. The embolized animals tended to be more edematous by the first film. CONCLUSION: Rather than any protective effect, bronchoesophageal artery embolization may increase edema. This model may be inappropriate for further investigation of the bronchial circulation in the development of human pulmonary edema.

Permanent percutaneous antegrade ureteral stent placement without transurethral assistance.

A simple, one-step, permanent, percutaneous, antegrade insertion of a ureteral stent is described, utilizing a double, pigtail catheter. No transurethral assistance is necessary. The advantages of this simplified technique are presented, and the necessary prerequisites for its application are discussed.

Diagnosis and treatment of fluid-filled renal structures in children with ultrasonography and percutaneous puncture.

The application of ultrasonographic and percutaneous needle puncture techniques in the diagnosis of various fluid-filled renal anomalies has permitted rapid delineation of anatomic detail, more definitive physiologic evaluation, and drainage, when necessary, in a safe and cost-effective manner. Its usefulness in children is emphasized in 6 illustrated cases of male infants with minimally or nonopacified renal anomalies, one of the more difficult diagnostic problems in pediatric urology.

Hepatic artery chemoembolization for management of patients with advanced metastatic carcinoid tumors.

BACKGROUND: Patients with advanced metastatic carcinoid tumors who have disease progression despite conventional therapy are left with few therapeutic options. Hepatic artery chemoembolization (HACE) may play a role in palliating these patients' symptoms. METHODS: Fifteen patients with biopsy-proven advanced bilobar hepatic carcinoid metastases who demonstrated progression of symptoms and/or tumor size despite treatment with somatostatin analogues were treated with intra-arterial chemotherapy and HACE to determine efficacy and safety. Five days of intra-arterial 5-fluorouracil (1 g/m2) were followed by HACE with adriamycin (60 mg), cisplatin (100 mg), mitomycin C (30 mg), and polyvinyl alcohol (Ivalon); 200 micron to 710 micron). Patients were continued on octreotide at the same dose (150 to 2000 microg subcutaneous q 8 hours) before, during, and after the procedure. RESULTS: Efficacy of treatment was assessed by comparing pretreatment and 3-month clinical, laboratory, radiographic, and quality of life parameters. Symptoms were improved in 8 of 12 patients who had diarrhea, 7 of 12 who had flushing, 9 of 12 who had abdominal pain, and in 4 of 7 who had malaise. Elevated tumor markers decreased in all patients. Biochemical markers (mean +/- SE) at 3 months decreased by 60% +/- 6% for 5-HIAA, 75% +/- 10% for chromogranin A and 50% +/- 7% for neuron-specific enolase. Tomographic assessment revealed tumor liquefaction in 10 of 13 patients. The Karnofsky performance status improved from a mean of 66 +/- 2 to 84 +/- 2 (P <0.001). Median follow-up was 16 months, with 13 deaths occurring from 1 week to 71 months after treatment. CONCLUSIONS: Hepatic artery chemoembolization improves symptoms of carcinoid syndrome, has a high tumor response rate, and improves short-term quality of life in this group of patients with advanced hepatic carcinoid disease.

Transcatheter arterial chemoembolization as primary treatment for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) in Western populations has historically been associated with poor survival. METHODS: In this study, we conducted a 7-year retrospective analysis of patients with HCC undergoing transcatheter arterial chemoembolization (TACE) at our institution and examined demographics, outcomes, and complications. RESULTS: During the period of study, 39 patients (25 male [64%], mean age 58 [range 17 to 86]) underwent a total of 78 chemoembolization treatments. During the same time period, an additional 31 patients received supportive care only. The majority of patients had late stage disease (American Joint Committee on Cancer stage III, IVa, or IVb) with no statistical difference noted between the two groups (P = 0.2). However, patients receiving supportive care only had significantly worse hepatic dysfunction by Child's classification (P = 0.005). Twenty-nine patients (74%) had documented cirrhosis, with hepatitis C being the most common cause in 11 of 29 (38%). In patients undergoing TACE, overall actuarial survival was 35%, 20%, and 11% at 1, 2, and 3 years with a median survival of 9.2 months, significantly improved over the group receiving supportive care only (P < 0.0001). Median survival for the group receiving supportive care was less than 3 months. Neither age nor stage had a significant impact on survival. The most common complications of TACE included transient nausea, abdominal pain, vomiting, and fever. CONCLUSIONS: TACE is a safe and effective therapeutic option for selected patients with HCC not amenable to surgical intervention.

Techniques of non-orthogonal magnetic resonance imaging and its clinical application.

A technique to obtain non-orthogonal magnetic resonance (MR) images in the body has been developed using a simple three-dimensional model (3-DM). Images were obtained with multiple non-orthogonal planes, without subjecting patients to uncomfortable oblique positions. Eighty-two patients were studied using non-orthogonal planes. Euler angle determinations (EAD) were developed for different anatomical locations as well as for multiple clinical situations. One or all three Euler angles were changed using the EAD to define any plane of orientation relative to reference orthogonal frame. In a series of 12 patients for postoperative evaluation of Mustard and Senning procedure, the demonstration of anastomotic site was superior with angled coronal planes when compared to the routine coronal views in 83% of the studies. With the use of EAD, acquisition time for non-orthogonal planes can be reduced. 3-DM aids in the understanding of the Euler angles and leads to multiple non-orthogonal planes.

Case report. Mycotic aneurysm of the superior mesenteric artery: report of a successful repair.

A case of a patient with a mycotic superior mesenteric artery aneurysm that was successfully repaired by the technique of restorative endoaneurysmorrhaphy is presented. Principles of diagnosis and management are delineated.

Practical aspects of gated magnetic resonance imaging of the pulmonary artery.

A practical clinical evaluation of the role of gated magnetic resonance imaging (GMRI) for the evaluation of congenital and acquired diseases of the pulmonary artery is presented, comparing GMRI to the already established usefulness of other various noninvasive and invasive imaging modalities.

Sonography of transjugular intrahepatic portosystemic shunts.

Transjugular intrahepatic portosystemic shunting (TIPS) is an effective procedure for relieving portal hypertension. Sonography can usefully assist portal vein puncture. Color and duplex sonography after TIPS demonstrates changes in hepatic vascular hemodynamics, detects complications, and confirms shunt patency. A large proportion of shunts will develop progressive stenosis over 12 months. Stenosis occurs because of pseudointimal hyperplasia in the stent or in the hepatic vein. Patent shunts are characterized by velocities in excess of 70 cm/s and hepatofugal flow in the portal circulation distal to the shunt. Although the cause of the stenosis can rarely be seen, velocities of less than 50 cm/s indicate shunt stenosis. Loss of cardiac pulsatility is another useful sign of shunt stenosis. Regular sonographic monitoring reliably detects stenosis, allowing stent revision and preventing recurrence of bleeding.

Quantitative evaluation of postembolized splenic tissue using technetium-99m sulfur colloid.

Tc-99m sulfur colloid scans were used to quantitate the percent of residual splenic tissue after partial splenic embolization (PSE) performed for the treatment of hypersplenism in 17 renal transplant patients. A liver-spleen phantom was designed which simulated the human liver and spleen configuration to evaluate the technique. This phantom contained a solution of tc-99m sulfur colloid, which allowed precise quantities of the spleen phantom volume to be displaced using lucite pseudo-emboli. After each lucite embolus, computer images of the spleen phantom were collected and analyzed in the same manner used for the transplant patients. Correlation of the actual volume displaced or embolized with the computer estimated values was 0.996 (P less than 0.001). This technique was superior to both CT and MRI, which were more difficult to perform and less precise in measuring a decrease in postinfarction functioning splenic tissue.