Gastric phytobezoar associated with impaired gastric motility in a patient with spinal cord injury

Impaired gastrointestinal motility as a result of interruption of sympathetic outflow is a common occurrence in the spinal cord injury (SCI) population. In addition, frequent use of medications with anticholinergic properties in this population results in further impairment of peristalsis resulting in gastrointestinal stasis. Since SCI patients often lack sensation below the level of injury, they may present with vague symptoms, which complicates the diagnosis of intestinal obstruction. We report the first case of gastric phytobezoar in a patient with T4 ASIA A paraplegia who presented with vague upper abdominal discomfort, anorexia, weight loss, and vomiting. Because mortality rates can be as high as 30% if phytobezoars remain untreated, gastrointestinal phytobezoars should be considered in the differential diagnosis of abdominal discomfort in SCI patients. Etiologic factors for phytobezoars are discussed for the general population and in particular, for patients with SCI.     

Venous air emboli occur during release of positive end-expiratory pressure and repositioning after sitting position surgery.

We studied the effect of positive end-expiratory pressure (PEEP) release and positioning on the occurrence of venous air embolism (VAE). Eighteen consecutive patients (8 women, 10 men; ASA grade I-III) undergoing neurosurgery in the sitting position were studied. After induction of anesthesia ventilation was controlled with a PEEP of 5 cm H(2)O in an oxygen-air gas mixture. A transesophageal echocardiographic (TEE) probe was inserted. Preoperatively, a patent foramen ovale was excluded in all patients. TEE monitoring was performed during surgery, during PEEP release at the end of surgery with the patient still in the sitting position, and during change of the patient position into the supine position. The severity of VAE was differentiated as follows: grade 1 = only microbubbles; grade 2 = microbubbles and decrease of end-tidal carbon dioxide partial pressure (PETCO(2)) by more than 1.5 mm Hg; grade 3 = microbubbles combined with a decrease of PETCO(2) by more than 1.5 mm Hg, and a decrease of mean arterial blood pressure by at least 20 mm Hg. During surgery, VAE with a grade of 1, 2 or 3 occurred in 7, 4, and 2 patients, respectively. After PEEP release, VAE of grades 1, 2, and 3 were observed in 7, 2, and 1 patients, respectively. During repositioning from sitting to supine position, VAE of grades 1, 2, and 3 was observed in 6, 1, and 1 patients, respectively. The patient with VAE grade 3 needed inotropic support until 2 h after surgery to maintain sufficient blood pressure. No patient showed any sign of paradoxical arterial embolism or cardiac dysfunction. We conclude that VAE occurs not only during surgery in the sitting position, but also with release of PEEP and during repositioning to the supine position. IMPLICATIONS: This study shows that venous air embolism (VAE) occurs not only during surgery in the sitting position but also during positive end-expiratory pressure release and repositioning of the patient into the supine position. Continuous monitoring for VAE should be performed until the patient is returned to the supine position.     

New insights into the interactions between T-cell costimulatory blockade and conventional immunosuppressive drugs

OBJECTIVE: To determine the precise in vivo interaction between T-cell costimulatory blockade and conventional immunosuppression in transplantation. SUMMARY BACKGROUND DATA: Blocking B7 or CD154 T-cell costimulatory activation pathways prevents allograft rejection in small and large animal transplant models and is considered a promising strategy for clinical organ transplantation. METHODS: A fully MHC-mismatched vascularized mouse cardiac allograft model was used to test the interactions between anti-CD154 or CTLA4Ig monotherapy and conventional immunosuppressive drugs in promoting long-term graft acceptance. The frequency of alloreactive T cell was measured by ELISPOT. Chronic rejection was examined by histology. RESULTS: Cyclosporine, tacrolimus, and anti-IL-2R monoclonal antibody therapy abrogated the effect of a single-dose protocol of anti-CD154 therapy. In contrast, rapamycin acted synergistically with anti-CD154 therapy in promoting long-term allograft survival. The addition of calcineurin inhibitors did not abolish this synergistic effect. Intense CD154-CD40 blockade by a multiple-dose schedule of anti-CD154 resulted in long-term graft survival and profound alloreactive T-cell unresponsiveness and overcame the opposite effects of calcineurin inhibitors. CTLA4Ig induced long-term graft survival, and the effect was not affected by the concomitant use of any immunosuppressive drugs. CONCLUSIONS: The widespread view that calcineurin inhibitors abrogate the effects of T-cell costimulatory blockade should be revisited. Sufficient costimulatory blockade and synergy induced by CD154 blockade and rapamycin promote allograft tolerance and prevent chronic rejection.     

The UniSpacer™: correcting varus malalignment in medial gonarthrosis

While options for operative treatment of leg axis varus malalignment in patients with medial gonarthrosis include several established procedures, such as unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA) or high tibial osteotomy (HTO), there has been little focus on a less invasive option introduced more recently: the UniSpacer™ implant, a self-centering, metallic interpositional device for the knee. This study evaluates clinical and radiological results of the UniSpacer™, whether alignment correction can be achieved by UniSpacer™ arthroplasty and alignment change in the first five postoperative years. Anteroposterior long leg stance radiographs of 20 legs were digitally analysed to assess alignment change: two relevant angles and the deviation of the mechanical axis of the leg were analysed before and after surgery. Additionally, the change of the postoperative alignment was determined one and five years postoperatively. Analysing the mechanical tibiofemoral angle, a significant leg axis correction was achieved, with a mean valgus change of 4.7 ± 1.9°; a varus change occurred in the first postoperative year, while there was no significant further change of alignment seen five years after surgery. The UniSpacer™ corrects malalignment in patients with medial gonarthrosis; however, a likely postoperative change in alignment due to implant adaptation to the joint must be considered before implantation. Our results show that good clinical and functional results can be achieved after UniSpacer™ arthroplasty. However, four of 19 knees had to be revised to a TKA or UKA due to persistent pain, which is an unacceptably high revision rate when looking at the alternative treatment options of medial osteoarthritis of the knee.     

Long-term survival of a patient with giant cell glioblastoma. Case report

The authors report on a patient who had undergone resection of a left-sided temporal giant cell glioblastoma at the age of 69 years and who survived for more than 17 years. This man had not undergone postoperative radiotherapy or adjuvant chemotherapy. He died at the age of 86 years without clinical evidence of tumor recurrence. Histologically, the lesion was characterized by highly pleomorphic tumor cells (including bizarre multinucleated giant cells) with high mitotic activity, large necroses, and prominent mononuclear infiltration. A point mutation in the TP53 tumor suppressor gene (c.524G>A; R175H) and no epidermal growth factor receptor gene amplification were revealed on molecular genetic analysis. No diagnostic chromosomal imbalances were identified on comparative genomic hybridization, although the average ratio profile for chromosome 10 indicated loss of 10p15 in a subpopulation of tumor cells. This patient is exceptional because tumor resection, probably in conjunction with a marked antitumor immune response, apparently resulted in eradication of the lesion.     

Comparison between bovine bone and titanium interference screws for implant fixation in ACL reconstruction: a biomechanical study

Introduction

The application of interference screws for the fixation of bone-patellar tendon-bone (BPTB) grafts is a well-established technique in anterior-cruciate ligament reconstruction. Interference screws derived from bovine compact bone are a biological alternative to metallic or biodegradable polymer interference screws.

Materials and methods

In 60 porcine specimens, the tibial part of an anterior-cruciate ligament reconstruction was performed using a BPTB graft. To secure the graft, either an 8-mm titanium interference screw or a self-made bovine interference screw (BC), or a commercial bovine compact bone screw (Tutofix^®) was used. The maximum failure load was determined by means of a universal testing machine with computer interface at a testing speed of 50 mm/min. In a second test series, cyclic sub-maximal load was applied to the test specimen from 40 to 400 N with a number of 1,000 load cycles and a frequency of 1 Hz. Subsequently, the maximum failure load was determined. The stiffness of the test specimen was investigated in both test series. Each type of interference screw was tested 10 times.

Results

A secure fixation of the grafts was achieved with all interference screws. In the experiments on the maximum load to failures, the titanium screws showed significantly higher failure loads than the Tutofix^® screws (P = 0.005). The stiffness of the grafts fixed with BC screws was significantly higher as compared to the fixation with Tutofix^® screws (P = 0.005). After cyclic sub-maximal loading, the maximum failure load of the titanium screws was significantly higher than that of the Tutofix^® screws (P = 0.033). The fixation of the BC screws showed a significantly higher failure load (P = 0.021) and stiffness (P = 0.032) than the Tutofix^® screw fixation. Except for two screw head fractures and two intra-tendinous graft ruptures, the failure mode was slippage in the interface between interference screw and bone plug.

Conclusion

Interference screws derived from bovine compact bone show similar good results as the titanium interference screws. Therefore, the safety and in vivo performance of products derived from xenogenic bone should be the focus of further investigations.     

Changes in spinal cord injury-induced gene expression in rat are strain-dependent.

BACKGROUND AND CONTEXT: The functional recovery of animals subject to experimental spinal cord injury (SCI) is dependent on the injury model as well as the species and strain of animal used. Previous studies have shown differences in rates and degree of recovery between rats of different strains. PURPOSE: We sought to explore the hypothesis that differences in gene expression are associated with differences in functional recovery. STUDY DESIGN/SETTING: Laboratory study involving cohorts of three different strains of rat. METHODS: We used the Impactor device to produce identical spinal cord contusion injuries in groups of Long Evans, Sprague-Dawley, and Lewis rats (10 each). The functional recovery of animals was assessed using the Basso, Beattie, and Bresnahan rating scale. Six weeks after injury, rats were killed and the spinal cords were harvested for deoxyribonucleic acid microarray analysis. Changes in gene expression compared with intraspecies controls (3 each) were assessed at the region of injury and at a rostral segment of the spinal cord. Selected genes were also studied with real-time polymerase chain reaction. RESULTS: We found that different strains tended to exhibit different patterns of functional recovery. There were differences between the strains in terms of gene expression. CONCLUSIONS: These results emphasize the importance of testing novel therapies for SCI in a variety of animal species before introduction into human trials. Further research into the influence of several gene products on functional recovery is needed.     

In vitro HIV-1 entry and replication in Langerhans cells may clarify the HIV-1 genome detection by PCR in epidermis of seropositive patients.

Being dendritic antigen-presenting cells in skin and mucous membrane, Langerhans cells (LC) occur in areas at risk for inoculation by human immunodeficiency virus (HIV), and the question whether LC act as a target, reservoir, or vector for transmission of HIV has given rise to much controversy. To address this question, we first analyzed the epidermal compartment of skin from patients seropositive for HIV DNA. Second, we tested the susceptibility of each cell type normally found in this compartment to in vitro infection by HIV-1. A non-denatured DNA was obtained from epidermal sheets after a thermochemical treatment of biopsies (0.5 M ethylenediaminetetraacetic acid (EDTA), pH 7.5 at 60 degrees C for 90 seconds). Optimization of amplification of viral genome was performed with three primer pairs derived from gag, env, and pol sequences. Polymerase chain reaction (PCR) products were analyzed by Southern blot. Viral genome was found in five of 11 HIV-seropositive patients. To control the permissivity of epidermal cell population for HIV, cells isolated from the epidermal sheet of normal skin by trypsinization were co-cultured with HIV-1-carrying promonocytic cells (U937) and observed by electron microscopy. After 3-6 h of co-culture, numerous virions were either tightly bound or apparently engaged in the process of internalization through receptor-mediated endocytosis. At day 4 of co-culture, some infected LC appeared to release mature viral particles through bud formation. The in vitro HIV-1 entry and replication in LC may confirm the presence of the HIV-1 genome by PCR in epidermis of seropositive patients. The consequences of the permissivity of LC for HIV on the antigen-presenting function remain to be determined.     

Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches

The expression of tumor-associated antigens (TAAs) might play a critical role in the control of minimal residual disease (MRD) in acute myeloid leukemia (AML), and therefore might be associated with clinical outcome in AML. In a DNA microarray analysis of 116 AML samples, we found a significant correlation between high mRNA levels of G250/CA9 and longer overall survival (P = .022), a similar trend with high mRNA levels of PRAME (P = .103), and a hint for RHAMM/HMMR. In contrast, for other TAAs like WT1, TERT, PRTN3, BCL2, and LAMR1, we found no correlation with clinical outcome. High expression of at least 1 of the 3 TAAs, RHAMM/HMMR, PRAME, or G250/CA9, provided the strongest favorable prognostic effect (P = .005). Specific T-cell responses were detected in 8 (47%) of 17 patients with AML in complete remission for RHAMM/HMMR-R3 peptide, in 7 (70%) of 10 for PRAME-P3 peptide, and in 6 (60%) of 10 for newly characterized G250/CA9-G2 peptide, a significant increased immune response compared with patients with AML patients who had refractory disease (P < .001). Furthermore, we could demonstrate specific lysis of T2 cells presenting these epitope peptides. In conclusion, expression of the TAAs RHAMM/HMMR, PRAME, and G250/CA9 can induce strong antileukemic immune responses, possibly enabling MRD control. Thus, these TAAs represent interesting targets for polyvalent immunotherapeutic approaches in AML.     

Ultrastructural localization of binding sites of sera from patients with linear IgA bullous dermatosis

The localization of the antigen recognized by IgA basement membrane zone (BMZ) antibodies from patients with linear IgA bullous dermatosis (LABD) has not been established. The aim of our study was to find out the binding sites for IgA-BMZ antibodies in LABD in adults and children and, for comparison, the binding sites for IgA antibodies in IgA cicatricial pemphigoid (IgA-CP). Our series comprised 21 sera from adult LABD, 4 sera from childhood LABD, and 2 sera from IgA-CP. The studies were performed using the sodium chloride split-skin method and indirect immunoelectron microscopy (IEM) with the use of the pre-embedding immunoperoxidase techinique on two substrates: monkey oesophagus and normal human skin. Of the 27 sera, 24 reacted with the epidermis (19 from adult, 4 from childhood LABD and 1 from IgA-CP) and at the electron microscopic level labelled the upper part of the lamina lucida (LL) and/or hemidesmosomes, and 2 reacted with the dermis (1 from typical adult LABD and 1 from IgA-CP) and labelled the sublamina densa (SLD) region. Two sera were negative in IEM. In conclusion, the study indicated that the localization of the antigens is similar in adult and childhood LABD, and in IgA-CP.Part of this work was presented during the Second Tricontinental Meeting of the Japanese Society for Investigative Dermatology, the Society for Investigative Dermatology and the European Society for Dermatological Research. October 1993, Kyoto, Japan