T-cell activation, proliferation, and memory after cardiac transplantation in vivo

OBJECTIVE: To study the response of alloantigen (H2Kb)-specific T cells to a H2b+ cardiac allograft in vivo. SUMMARY BACKGROUND DATA: The response of T cells to alloantigen has been well characterized in vitro but has proved more difficult to assess in vivo. The aim of these experiments was to develop a model of T-cell-mediated rejection where the response of T cells after transplantation of a cardiac allograft could be followed in vivo. METHODS: Purified CD8+ T cells from H2Kb-specific TCR transgenic mice (BM3; H2k) were adoptively transferred into thymectomized, T-cell-depleted CBA/Ca (H2k) mice. These mice were then transplanted with a H2Kb+ cardiac allograft. Using four-color flow cytometry, the proliferative response, modulation of activation markers, and potential cytokine production of the H2Kb-specific T cells was assessed after transplantation. RESULTS: Consistent rejection of H2Kb+ cardiac allografts required the transfer of at least 6 x 10(6) CD8+ H2Kb-specific T cells. Short-term analyses revealed that the transgenic-TCR+/ CD8+ T cells proliferated and became activated after transplantation of an H2Kb+ cardiac allograft. Fifty days after transplantation, the transgenic-TCR+/CD8+ T cells remained readily detectable, bore a predominantly memory phenotype (CD44hi), and rapidly produced interleukin 2 and interferon-gamma on in vitro restimulation. CONCLUSIONS: These data show that the activation of alloantigen-specific T cells can be followed in vivo in short-term and long-term experiments, thereby providing a unique opportunity to study the mechanisms by which T cells respond to allografts in vivo.     

Surgical treatment of aortic arch hypoplasia in infants and children with biventricular hearts

Background. Results of aortic arch reconstruction in the setting of biventricular physiology are well documented in the adult population, however, in children, surgical outcome of this subgroup of patients is less clear.

Methods. We studied the clinical outcomes of 37 children aged 8 days to 15 years (median 26 months), who underwent aortic arch reconstruction for arch hypoplasia from 1982 to 1997. The children were divided into three groups: Group 1 (20 patients) had isolated aortic arch lesions, Group 2 (13 patients) had associated intra-cardiac pathology yet conserving a biventricular physiology, Group 3 (4 patients) had Williams Syndrome. Previous interventions for coarctation had been performed in 30 patients (81%). Arch repair consisted of a patch aortoplasty in the majority of patients (35 of 37 children).

Results. Operative mortality occurred in 5 children, 4 in Group 2 (31%), 1 in Group 3 (25%) and none in Group 1. Permanent neurological complications occurred in 2 children (5 %). During the follow-up, which ranged from 1 month to 8 years, balloon angioplasty for arch obstruction was required in 1 child. There was one late death, associated with a subsequent intra-cardiac repair.

Conclusions. Aortic arch surgery in children with isolated arch hypoplasia, is associated with excellent early and late survival in addition to a low reintervention rate. Alternative perfusion and operative strategies must be implemented in infants with associated intra-cardiac anomalies to improve results.     

Technetium-99m sestamibi imaging in paediatric neuroblastoma and ganglioneuroma and its relation to P-glycoprotein

Imaging with technetium-99m sestamibi offers a non-invasive approach to detect the presence of functional P-glycoprotein (Pgp), one of the major causes of multidrug resistance, in human malignancies. A clinical role for Pgp has been suggested in the subpopulation of primary neuroblastoma without amplification of the proto-oncogene MYCN. We wanted to evaluate the usefulness of 99mTc-sestamibi scintigraphy in the screening of neural crest tumours for the presence of Pgp. In ten children suffering from MYCN-negative neuroblastoma, ganglioneuroblastoma or ganglioneuroma, 99mTc-sestamibi imaging was performed at initial diagnosis. All patients underwent planar imaging 20-30 min and 3.5-4 h after intravenous injection of 740 MBq/1.73 m2 99mTc-sestamibi. Tumour to normal tissue ratios, as well as washout rates, were determined and compared with in vitro flow cytometric analysis of Pgp expression and function. Pgp expression was analysed flow cytometrically with the monoclonal antibodies 4E3 and MRK16, and Pgp function was evaluated by means of rhodamine 123 uptake and efflux either in the absence or in the presence of the Pgp inhibitor verapamil. In nine of ten patients, we found that the intratumoral 99mTc-sestamibi activity was comparable to the background activity, which might be suggestive of Pgp presence. This was confirmed flow cytometrically in all but one patient. 99mTc-sestamibi enhancement was seen in the primary tumour and the bone marrow metastases of one of the ten patients, and this result was concordant with a negative Pgp status. The findings presented suggest that 99mTc-sestamibi imaging results might correlate with the presence of functional Pgp in neural crest tumours without MYCN amplification.     

Time-resolved MR angiography of the upper abdomen: initial clinical experience

In this study, thirty-eight patients with a variety of upper abdominal diseases were examined with three-dimensional time-resolved MR angiography (7 sec/data set). Visualisation of arterial and venous anatomy was excellent in the majority of patients. Moreover, subtraction images could be calculated and organ perfusion could be assessed. It is concluded that this technique opens new perspectives for a comprehensive evaluation of vascular and parenchymal disease. Received: 14 April 1998; Revision received: 23 October 1998; Accepted: 9 November 1998     

MR imaging of hypervascular liver tumors: timing optimization during the arterial phase

To analyze the optimal timing strategy for the detection of hypervascular liver tumors during the arterial phase of magnetic resonance (MR) imaging, a test examination after injection of 2 mL of gadopentetate dimeglumine was performed in 47 patients. The time course of the tumor-to-liver contrast-to-noise ratio (CNR) for all studies together was determined relative to the start of injection, the time of peak aortic enhancement, and the time of peak enhancement in the tumor. All studies were grouped together and the highest CNR was transiently observed at the time of peak tumor enhancement. This CNR was significantly higher than those observed at fixed delays after peak aortic enhancement. However, the CNRs at peak tumor enhancement+/-1.5 seconds did not differ significantly from those obtained after peak aortic enhancement. Finally, the CNRs obtained at fixed delays after the start of injection remained significantly lower. In hypervascular liver tumors, a higher CNR can be obtained during the arterial phase when the MR imaging delay is determined relative to the time of peak enhancement in the tumor or the aorta rather than being fixed after the start of contrast material injection. Timing based on the enhancement profile in the tumor rather than in the aorta should be performed only if rapid MR imaging is available with a time resolution of about 1.5 seconds to image the whole liver.     

The hemodynamic effects of cell-free hemoglobin during general and epidural anesthesia

Local anesthetics inhibit edema and improve circulation in experimental burns. We evaluated the effect of topical local anesthetics on human skin burns in volunteers using computerized color analysis that allowed repeated noninvasive quantitative measurements. A standardized partial-thickness burn (1 cm2) was induced in one forearm of 10 healthy volunteers and in the opposite forearm a week later. The burned areas were treated with lidocaine/prilocaine cream (EMLA; Astra, Sweden) or a placebo cream for 1 h. The experimental skin area was photographed before and 1, 2, 4, and 12 h postburn. Digitized images were evaluated using normalized red-green-blue and Hue-Saturation-Intensity. Differences in erythema between skin treated with EMLA and placebo were not significant during the first 4 h postburn. However, 12 h postburn, a pronounced decrease in the degree of erythema was observed in EMLA-treated skin compared with placebo-treated skin. We conclude that topical local anesthetics administered for 1 h postburn significantly reduces the duration of erythema after a mild thermal injury, which suggests a potential use in clinical practice in the treatment of minor skin burns. IMPLICATIONS: Burn injury constitutes a serious type of tissue damage that activates inflammatory mechanisms, often causing pain, disfiguration, or malfunction. We treated burns using an anesthetic cream and demonstrated a reduction in burn-induced inflammation by using computer-based color image analysis.     

Laparoscopic-assisted continent urinary diversion in obese patients

BACKGROUND AND PURPOSE: The Pfannenstiel incision provides good access to the bladder and bladder neck for major reconstructive surgery in the thin patient, whereas a midline incision is often necessary to get adequate exposure in the obese patient. We describe our experience using laparoscopic-assisted continent urinary diversion in conjunction with other bladder and bladder neck surgery in obese patients. PATIENTS AND METHODS: Three female patients (mean age 18; mean weight 175 pounds) with neurogenic bladder underwent Mitrofanoff appendicovesicostomy continent urinary diversion to the umbilicus and pubovaginal sling. An umbilical port for the telescope and two lateral ports were used. Once the appendix and right hemicolon had been completely mobilized up to the hepatic flexure, reconstruction was completed through a low Pfannenstiel incision. RESULTS: There were no laparoscopic complications. None of the laparoscopic port sites was visible postoperatively, as one was in the base of the umbilicus, and the other two had been incorporated into the Pfannenstiel incision. With a mean follow-up of 1 year, all patients were continent and catheterizing their umbilicus easily. Pfannenstiel incisions were well healed, and the patients were quite satisfied with their cosmesis. CONCLUSION: Laparoscopic-assisted Mitrofanoff appendicovesicostomy continent urinary diversion to the umbilicus can be performed in conjunction with a Pfannenstiel incision to complete major bladder and bladder neck surgery in the obese patient with good postoperative cosmesis. This procedure represents a nice compromise between a very lengthy bladder reconstructive procedure done purely laparoscopically and a midline incision with good exposure but suboptimal cosmesis.     

Diffuse and localized pigmented villonodular synovitis: evaluation of treatment of 38 patients

We performed a retrospective study of 38 patients with pigmented villonodular synovitis (PVNS) to evaluate the treatment and functional results. The mean age of the patients was 32 (range 12-72) years at the time of treatment. Three types of PVNS have been identified: localized nodules in 9 patients, diffuse PVNS of the entire synovial membrane in 26, a combination of a diffuse involvement of the synovial membrane and an extra-articular presentation in 1, and extra-articular lesions in 2. The location of the lesions was knee (n = 31), hip (n = 3), ankle (n = 2), femoral triangle (n = 1), and gluteal region (n = 1). The procedures performed were surgery alone, surgery combined with radiosynovectomy and radiosynovectomy only. A follow-up was done after a mean of 4 (range 1-19) years in 34 patients. A functional evaluation according to the Musculoskeletal Tumor Society was performed in 31 patients. The mean functional evaluation score of 34 patients was 24 (range 15-30). Most of the ratings were excellent or good, in 6 cases fair, and in 2 cases poor. This study demonstrates that the functional results are good despite residual or recurrent disease; in addition, we showed that functional evaluation after treatment gives an optimal view of the impact and results of the operation.