Long-term follow-up after surgical treatment of adolescent idiopathic scoliosis using high-density pedicle screw constructs: Is 5-year routine visit required?

PURPOSE: The objective of this study is to determine whether routine follow-up 5 years after adolescent idiopathic scoliosis (AIS) surgery is likely to affect postoperative care for patients treated with high-density pedicle screw constructs, when routine 2-year follow-up has been performed. METHODS: We reviewed 80 patients undergoing surgery for AIS using high-density pedicle screw constructs and followed routinely 2 and 5 years after surgery. Quality of life (QOL) was assessed using the SRS-30 outcome questionnaire. Reoperations occurring between 2 and 5 years after surgery were identified. RESULTS: Curve correction and QOL were similar between 2- and 5-year visits. Two patients required revision surgery after presenting during unplanned visits between the 2- and 5-year follow-ups. One patient presented at the routine 5-year visit with an asymptomatic undisplaced rod fracture without loss of correction, and it was decided to follow-up only as needed. CONCLUSIONS: In AIS patients for whom routine follow-up 2 years after surgery using high-density pedicle screw constructs was uneventful, additional routine 5-year follow-up is not likely to affect postoperative care and revision rate. Patients developing complications and needing reoperation between 2 and 5 years after surgery will most likely present during unplanned visits rather than during routine follow-up appointments. Easy access to emergent visits on an as-needed basis is therefore important for this population if routine 5-year follow-up is not planned. These slides can be retrieved under Electronic Supplementary Material.

Study of patient positioning on a dynamic frame for scoliosis surgery.

The goal of this clinical trial was to measure patient geometry on a dynamic positioning frame in various prone positions. Fourteen subjects (2 males and 12 females) were recruited from the scoliosis clinic at Ste-Justine Hospital on a volunteer basis. The subjects were AIS patients who were potential candidates for surgery. The Cobb angle, averaged 50 degrees (32 degrees-64 degrees). The mean age was 14.1 years (11-17). A Polaris system (Northern Digital inc, Canada) with 10 passive reflective markers was used to measure various indices of the patient's trunk geometry. Acquisitions were made while the unanaesthetized patient was in five different prone positions: I similar to the standard positioning on a Relton-Hall frame; II addition of a force applied to the ribcage at the apex of the curve; III application of a force at the apex of the curve in the lumbar region; IV, the shoulder pads were elevated to increase the patient's kyphosis; V adjustment of each pad and the application of thoracic and lumbar forces to obtain an optimal correction. The measurements of trunk geometry at each position were compared using position I as a base. A paired student t-test determined a significant difference between positions. When comparing position I to position II there was a significant difference and correction of the rib hump. There was also a significant change in shoulder angle that resulted in over correction. Position III had a significantly negative change in the rib hump. During position IV, there was a measurable increase in kyphosis. During the optimal correction, position V, a significant increase in spine length was observed as well as a significant correction in rib hump and shoulder angle. Patient trunk geometry can be improved by the application of different forces on a dynamic positioning frame. Caution is necessary as over correction and unintended negative effects were observed. The optimal patient position has not yet been found and future studies are directed at determining this.

Natural history of Epstein-Barr virus infection in a prospective pediatric cohort born to human immunodeficiency virus-infected mothers.

To determine whether Epstein-Barr virus (EBV) constitutes a contributing factor in AIDS and, conversely, whether the human immunodeficiency virus (HIV) alters the course of primary EBV infection in a pediatric population, 62 children born to HIV-infected mothers and prospectively followed were evaluated. EBV infection was documented by EBV-specific serology and polymerase chain reaction and by clinical history. HIV infection status was determined according to the Centers for Disease Control and Prevention pediatric classification system. Demographics from HIV-infected and HIV-uninfected children were comparable. The data suggest that HIV-infected children may acquire primary EBV infection earlier in life. The incidence of accompanying splenomegaly or hepatomegaly (or both) around the time of EBV seroconversion was higher among HIV-infected children than among HIV-uninfected children. In contrast, HIV disease progression and HIV-1 RNA load did not seem to be influenced by primary EBV infection.

Antibody responses to two Epstein-Barr virus (EBV) nuclear antigens (EBNA-1 and EBNA-2) during EBV primary infection in children born to mothers infected with human immunodeficiency virus.

A variety of antibody response patterns to the latent Epstein-Barr nuclear antigen (EBNA) family have been described in different groups of subjects infected with Epstein-Barr virus (EBV). The purpose of this study was to characterize the immune response to two EBNA proteins, EBNA-1 and EBNA-2, in a population of children who were born to mothers infected with HIV and who underwent EBV seroconversion. Serial serum specimens from 33 children (nine were infected with HIV, and 24 were not infected) were evaluated for the presence of antibodies to EBNA-1 and EBNA-2 by anticomplement immunofluorescence. All the EBNA serology profiles observed for children in our study who were not infected with HIV were consistent with those described for immunocompetent hosts with acute EBV infection, i.e., development of antibodies to EBNA-1, often preceded by the appearance of a humoral immune response to EBNA-2. In contrast, following EBV primary infection in HIV-infected children, antibodies to EBNA-2 arose after antibodies to EBNA-1 and tended to persist. Further studies are needed to investigate the role of EBNA-2 serology as a prognostic marker in HIV-infected children.

Epstein-Barr virus transmission from a blood donor to an organ transplant recipient with recovery of the same virus strain from the recipient's blood and oropharynx.

A previous study (Savoie et al, Blood 83:2715, 1994) identified eight transplant patients who acquired Epstein-Barr virus (EBV) infection during the peritransplant period. Three of these patients subsequently developed B-cell lymphoproliferative disease within 4 months of transplantation. Among these, there was a 16-year-old liver transplant patient who was negative for EBV at the time of transplant and who received an EBV-negative organ. After transplant, this patient was transfused with 9 U of packed red blood cells. Eight of the donors were EBV-positive and one was EBV-negative. We succeeded in obtaining spontaneous lymphoblastoid cell lines (LCLs) from the blood of three of these donors, one of whom also yielded a cord-blood line established with his throat-wash EBV. Blood from a fourth donor did not yield an LCL, but his throat washing did have transforming activity when inoculated onto cord-blood leukocytes. We initially could establish spontaneous LCLs only from the recipient's blood. However, a throat-wash sample taken 11 weeks later did show transforming activity. The recipient was shown to have acquired the EBV infection from one of eight EBV-seropositive blood donors. Analysis of fragment length polymorphisms after polymerase chain reaction amplification of the EBV BamHI-K fragment was used to establish strain identity. Western blot analysis for existence of size polymorphisms in three classes of Epstein-Barr nuclear antigens (EBNA-1, EBNA-2, and EBNA-3) confirmed the DNA results. It is noteworthy that the blood donor responsible for transmitting his EBV strain to the recipient had experienced clinical infectious mononucleosis 15 months before donating blood. Our results may, thus, indicate a requirement for leukodepletion of blood destined for immunosuppressed EBV-negative patients. Finally, blood donors with a recent history of infectious mononucleosis should probably be identified so that their blood is not given to EBV-negative transplant patients.

Anti-B cell antibodies for the treatment of monoclonal Epstein-Barr virus-induced lymphoproliferative syndrome after multivisceral transplantation.

Epstein-Barr virus-induced lymphoproliferative syndrome (EBV-LPS) is associated with OKT3 therapy in transplant patients. Response to chemotherapy or radiation is generally poor, while polyclonal EBV-LPS has had favorable responses to therapy with CD21 and CD24 monoclonal antibodies. Oligoclonal disease has not been previously reported to respond to therapy with CD21 and CD24. We report a 27-y old woman who developed a monoclonal EBV-LPS (confirmed by southern analysis of tumour for EBV DNA) after 180 mg of OKT3 for a multivisceral transplant. The patient achieved clinical remission for more than 2 months, but later died from cytomegalovirus pneumonia. Levels of CD21 and CD24 were > 2000 ng/ml during therapy and no human anti-mouse antibodies were formed. Peripheral blood B cells were cleared during therapy. We conclude that CD21 and CD24 monoclonal antibodies may be of value in the therapy of oigoclonal EBV-LPS, and merit further study.

Direct correlation between the load of Epstein-Barr virus-infected lymphocytes in the peripheral blood of pediatric transplant patients and risk of lymphoproliferative disease.

The Epstein-Barr virus (EBV) is known to cause posttransplant lymphoproliferative disease (PTLD) in immunosuppressed transplant patients. The results of this pilot study showed that all EBV- patients pretransplant experienced primary EBV infection within the first 3 months after transplant surgery. Virtually all of these patients had a higher burden of EBV-infected cells in their peripheral blood (PB) after infection by EBV than did the EBV+ pretransplant group when tested at the same intervals posttransplant. Salivary EBV titers also increased in most patients, but the difference between the two groups was statistically significant only at 12 months, whereupon EBV+ patients showed higher titers compared with EBV- (alpha < 0.053). Also, polymerase chain reaction amplification followed by Southern blotting was performed to detect EBV sequences in PB mononuclear cells. This technique allowed confirmation of the blood culture results and constituted a faster alternative compared with the culture assay. The highest increase in the number of EBV-infected lymphocytes at 3 months posttransplant obtained from PB was seen in a patient who developed fatal PTLD and in another with protracted infectious mononucleosis. Thus, the number of EBV-infected cells in PB was found to correlate positively with risk of development of PTLD at 3 months posttransplant in our group of pediatric transplant patients. This study showed that quantitative lymphocyte culture of PB was an accurate index of immunosuppression and a reliable method for assessing the risk of PTLD development.

Comparison of novel synthetic peptide-based DETECT-RUBELLA enzyme immunoassays with Enzygnost and IMx for detection of rubella-specific immunoglobulin G.

Enzyme immunoassays (EIAs) using synthetic peptides SP-E1 and SP-E1E2 (DETECT-RUBELLA [Bio-Chem]) were compared with two viral lysate-based EIAs (Enzygnost [Behring] and IMx [Abbott]) for the detection of rubella virus-specific immunoglobulin G antibodies. Sensitivities of 94.7, 100, 98.6, and 100% and specificities of 100, 97.4, 100, and 73.7% were found for the SP-E1, SP-E1E2, Enzygnost, and IMx EIAs, respectively.

Radioimmunoprecipitation in the diagnosis of chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus (EBV) infection occurs sporadically in a small fraction of individuals infected with EBV. A clear definition of the disease and an unambiguous diagnostic test are still lacking. In an attempt to identify a serologic marker to facilitate the diagnosis, immunoblot and radioimmunoprecipitation assay (RIPA) were compared with standard immunofluorescence on 39 available sera. Results by RIPA revealed that antibodies to a 120 kDa viral protein correlated with the presence of chronic active EBV infection; these antibodies were not detected in sera from other EBV-seropositive individuals, with the exception of one of two patients with ataxia telangiectasia. Also, RIPA was the most sensitive technique for detecting EBV antibodies in sera weakly or doubtfully positive for antibody to EB viral capsid antigen by indirect immunofluorescence. All these sera had antibodies to the 150 kDa protein, also known as p160, the major viral capsid antigen.

Comparison of a whole-virus enzyme immunoassay (EIA) with a peptide-based EIA for detecting rubella virus immunoglobulin G antibodies following rubella vaccination.

A total of 250 human serum samples were tested for rubella virus immunoglobulin G antibodies by two enzyme immunoassays (EIAs), one using whole rubella virus antigen and the other based on the use of synthetic peptide antigen. The samples were taken from 125 volunteers before and after their immunization with the RA 27/3 rubella vaccine. This study indicates that a synthetic peptide-based EIA can favorably replace current viral lysate-based EIAs to detect rubella virus antibodies following immunization. Because the synthetic peptide used in this newly developed EIA represents a putative neutralization epitope of the rubella virus, it could also be instrumental in determining rubella immune status and in assessing vaccine program efficiency.

Lack of scientific evidence for the treatment of lateral epicondylitis of the elbow. An attempted meta-analysis.

We have reviewed 185 articles published since 1966 to assess the scientific evidence for methods of treatment for lateral epicondylitis of the elbow. Of the 185 articles, 78 discussed treatment, but since the natural history of the syndrome is uncertain we considered only those series with concurrent control groups. Only 18 of these were randomised and controlled studies. We then graded these papers for scientific validity, using the methods of Chalmers et al (1981). The mean score of the 18 articles was only 33%, with a range from 6% to 73%. A minimum of 70% is required for a valid clinical trial, and we therefore concluded that there was insufficient scientific evidence to support any of the current methods of treatment. There were too many methodological differences to allow a quantitative meta-analysis, but our qualitative review established the importance of the natural evolution of the syndrome and of the placebo effect of all treatments. Properly designed, controlled trials are needed.

Lack of effect of peroral acyclovir for the treatment of acute infectious mononucleosis.

Perorally administered acyclovir was evaluated in the therapy of acute infectious mononucleosis in a multicentered, randomized, double-blind, placebo-controlled trial. A total of 120 patients received 600 mg of acyclovir or placebo five times daily for 10 days. All patients were entered into the study within 7 days of symptom onset and had a positive Monospot test. Analysis of mean values and time to resolution of fever, lymphadenopathy, weight change, hepatomegaly, splenomegaly, liver function tests, atypical lymphocytes, hours of bed rest, sense of well-being, and return to normal activities revealed no significant differences. There was a trend toward suppression of Epstein-Barr virus excretion in the oropharynx in acyclovir recipients. No toxicity was detected in patients treated with acyclovir. Under the conditions of the study, there was no evidence that treatment with perorally administered acyclovir affected the course of infectious mononucleosis.

The diagnosis of Epstein-Barr virus-associated polymorphic B cell lymphoma in immunocompromised patients: Review of methods.

Polymorphic B cell lymphoma and diffuse B cell lymphoproliferation associated with Epstein-Barr virus infection is increasingly reported in immunodeficient patients. Accurate diagnosis of these pathologies is essential because the appropriate treatment regimens for the patients in question differ from those for patients with other lymphoproliferative diseases. Two complementary techniques are currently used in the diagnosis and characterization of Epstein-Barr virus-associated B cell lymphomas and diffuse B cell lymphoproliferation. Immunofluorescence allows specific detection of Epstein-Barr nuclear antigens in lymphomatous tissue. Molecular hybridization with the Bam H1-W and/or Bam H1-NJ probes confirms the presence of the Epstein-Barr virus genome in tumour cells. The Bam H1-NJ probe is also useful in determining the clonality of the tumour and the replication mode, episomal or linear, of the viral genome. The polymerase chain reaction method allows detection of the Epstein-Barr virus genome within 24 h in these tumours and is more sensitive.

Epstein-Barr virus polymorphic B-cell lymphoma associated with leukemia and with congenital immunodeficiencies.

Polymorphic B-cell lymphoma seen in four patients with congenital immunodeficiencies and in two patients with leukemia receiving chemotherapy was associated with the Epstein-Barr virus (EBV). The tumors had characteristic histologic features: they were polymorphic consisting of a mixture of lymphoblasts and differentiated cells including plasma cells, and areas of hemorrhagic necrosis were prominent. The tumors were either polyclonal, monoclonal, or multiclonal. Patients with congenital immunodeficiencies who developed these tumors died despite radiotherapy, corticosteroids plus acyclovir, or a combination of intravenous (IV) immunoglobulins and alpha 2 interferon. Patients with leukemia recovered when immunosuppressive drugs were discontinued and leukemia has not recurred over a period of 2 and 4 years, respectively, in the two patients.

Brief report: killer cell defect and persistent immunological abnormalities in two patients with chronic active Epstein-Barr virus infection.

Two members of a family have manifested a syndrome of chronic active Epstein-Barr virus (EBV) infection. A father and his daughter suffered prolonged or recurrent mononucleosis, with splenomegaly, anemia, and intermittent fever; persistent immunological abnormalities included defective natural killer (NK) cytotoxicity, inverted CD4/CD8 ratios, hyper IgG1, high EBV viral capsid antigen (VCA) and early antigen (EA) antibodies, and low or undetectable EBV nuclear antigen (EBNA) antibody titers. The EBV seronegative member of the family was free of these abnormalities. However, NK activity in the seronegative individual was low-normal and its EBV-specific antibody-dependent K-cell cytotoxicity (EBV-ADCC) was abnormally low, suggesting that this K-NK cell defect may be primary. The father, who suffered from the syndrome for more than 15 years, lacked (or lost) antibodies to EBV-envelope and infected cell membranes, such as antibody-dependent cellular cytotoxicity (ADCC), neutralizing (NT), and gp 350/220 antibodies. Slow improvement over a period of years was heralded by rising NK cytotoxicity.

Epstein-Barr virus related lymphoepithelioma-like carcinoma of lung.

A malignant neoplasm localized to the lung is reported in a rather unusual host: a 40-year-old female, nonsmoker, of South-East Asiatic origin. The histology was of nasopharyngeal-like carcinoma character and ultrastructural examination confirmed a diagnosis of nonkeratinizing, poorly differentiated squamous cell carcinoma. The clinicopathologic findings were more suggestive of a primary pulmonary origin than the manifestation of an occult nasopharyngeal primary. The immunological profile was highly suggestive of an Epstein-Barr virus (EBV) associated epithelial neoplasia. This case might widen the spectrum of EBV-associated neoplasia, by inclusion of lower respiratory tract as a target organ.

Biomolecular analysis of a defective nontransforming Epstein-Barr virus (EBV) from a patient with chronic active EBV infection.

A virus recovered from the saliva of a child with chronic active Epstein-Barr virus (EBV) infection for 8 years was shown to induce EBV early antigen (EBV-EA) in Raji cells and to be expressed into EBV-EA in fresh EBV-negative peripheral blood leukocytes. However, it did not replicate its DNA. Oropharyngeal epithelial cells scraped from recurrent mouth lesions were similarly positive for EBV-EA. DNA extracted from these cells and digested with BamHI contained a 6-kilobase-pair fragment homologous to BamHI fragment V and B1 EBV DNA probes. Furthermore, Southern blots of the BamHI and EcoRI digests of the DNA extracted from the cell lines of the patient (transformed with EBV strain B95-8) and of her mother (spontaneous) revealed, in addition to the expected BamHI G, H, H2, and B1 fragments used as probes, additional shorter ones of a presumably endogenous defective virus.