Humoral immune transcriptome signature in myelomeningocele patients.

INTRODUCTION: Myelomeningocele (MMC) results from incomplete closure of the neural tube, and has a complex multifactorial etiology, including an inflammatory microenvironment. OBJECTIVE: We evaluated the contribution of humoral immune response for development of inflammatory milieu. METHODS: Using public repository Gene Expression Omnibus (GEO), we retrieve dataset transcriptome from the amniotic fluid of ten fetuses with myelomeningocele and ten healthy control fetuses to found differential gene expression associated with disturbances and inflammatory signatures in MMC. The identified DEGs were submitted to enrichment, network, and matrix correlation analyses. RESULTS: Our initial analysis revealed 90 DEGs in MMC, mainly associated with signaling pathways of inflammation, including the immune modules, humoral immune response and IFN-type I signatures. Protein-protein analysis (PPI) revealed an association with three protein networks; positive regulation of B cell proliferation constituted the largest network. Matrix correlation analyses showed that MMC alters the co-expression of genes related to inflammatory processes that promote microenvironment inflammation. CONCLUSION: These results revealed an altered humoral immune response in MMC patients, contributing to an inflammatory profile and providing opportunities for identifying potential biomarkers in myelomeningocele disease.

In utero repair of myelomeningocele with autologous amniotic membrane in the fetal lamb model.

BACKGROUND: Despite advances in prenatal repair, myelomeningocele (MMC) still produces devastating neurologic deficits. The amniotic membranes (AM) are a biologically active tissue that has been used anecdotally for human fetal MMC repair. This study evaluated the use of autologous AM compared to skin closure in an established fetal MMC model. METHODS: Seven fetal lambs underwent surgical creation of MMC at gestational age of 75days followed by in utero repair at gestational age of 100days. Lambs were repaired with an autologous AM patch followed by skin closure (n=4) or skin closure alone (n=3). Gross necropsy and histopathology of the spinal cords were performed at term to assess neuronal preservation at the lesion. RESULTS: An increase in preserved motor neurons and a larger area of spinal cord tissue were seen in AM-repaired lambs, as was decreased wound healing of the overlying skin. Loss of nearly all spinal cord tissue with limited motor neuron preservation was seen in skin only-repaired lambs. CONCLUSIONS: AM-repaired lambs showed increased protection of spinal cord tissue compared to skin only-repaired lambs, but the overlying skin failed to close in AM-repaired lambs. These results suggest a potential role for AM in fetal MMC repair that warrants further study.

Prevalence of sensitivity signals to latex in meningomyelocele patients undergoing multiple surgical procedures.

BACKGROUND AND OBJECTIVES: The number of patients allergic to latex has increased significantly. It is crucial to recognize the cases in order to prevent and apply adequate treatment. The objective of this study was to evaluate the prevalence of allergy to latex in meningomyelocele patients. MATERIALS AND METHODS: A retrospective evaluation of medical records of patients with meningomyelocele diagnosis from January 2002 to December 2007 was conducted. Patients were grouped into allergics and non-allergics. The comparison of groups for gender was made by the Chi-Squared test, the Student's t test was used to compare age, and Mann-Whitney test was used to compare groups for clinical manifestations of allergy, number of procedures under anesthesia, hospital admissions and vesical catheterizations. RESULTS: The mean number of procedures under anesthesia was 7 in the group with allergy and 4 in the group without allergy; this difference was statistically significant (p=0.028). The mean number of hospital admissions was 4.5 in the group with allergy and 3.4 in group without allergy and mean vesical catheterization was 24.5 in allergic patients and 21.7 in non allergic ones. CONCLUSIONS: Meningomyelocele patients undergoing multiple procedures under anesthesia have high risk of developing clinical signals of allergy to latex. It is necessary that patients with meningomyelocele diagnosis should undergo exclusively latex-free procedures, avoiding high risk of sensitization and its complications. Specific tests to evaluate sensitization, genetic markers and latex-fruit relationship may contribute to a better understanding of risk factors related to allergy to latex and ways to prevent it.

Risk factors for latex sensitization in young children with myelomeningocele. Clinical article.

OBJECT: Patients with myelomeningoceles (MMCs) are at increased risk of latex allergy and sensitization. Number of surgeries and history of atopy are known risk factors. The object of this study was to evaluate the role of diagnostic procedures and nonsurgical treatments in latex sensitization in young patients with MMC. METHODS: Seventy-three children with MMC were included in the study. For each child a questionnaire was administered and serum determination of IgE was performed, and 62 children underwent skin prick tests (SPTs), 60 of which had reliable results. Multivariate logistic regression modeling was performed, using latex sensitization as the dependent variable. RESULTS: The mean age of the 73 patients was 3.8 years. The SPT results were positive in 30.6%, whereas results of testing for latex-specific IgE were positive in only 8.2%. In univariate analysis, history of untethering, barium enema, and number of clean intermittent catheterizations (CICs) per day were significantly associated with positive results on the SPT. Although the number of surgical procedures was significantly higher in patients who had shunts, no significant relationship between the presence of a shunt and latex sensitization was seen. CONCLUSIONS: The young age of the patients in this study may account for the low prevalence of latex sensitization that was found. In young patients with MMC, the numbers of CICs per day, a history of untethering, circumcision, and a barium enema performed without latex-free equipment could be risk factors for latex sensitization. The use of latex-free gloves in all procedures performed in these cases, nonlatex polyvinyl chloride catheters in CIC, and ordinary nonballoon tips in barium enemas could decrease the risk of sensitization.

Latex sensitisation and allergy in children with myelomeningocele.

INTRODUCTION: Children with spina bifida (SB) have a high degree of exposure to latex products as a consequence of repeated surgical procedures, implantation of latex-containing materials and catheterisation. The consequence is a higher incidence of latex allergic reactions. OBJECTIVE: The aim of this study is to evaluate the prevalence of latex sensitisation and allergy in a population of children with myelomeningocele (MMC) and to assess the role of associated risk factors. RESULTS: Forty-eight percent of the patients (29 out of 60) showed a latex sensitisation with specific IgE >0.7 kU/l while 15% (9 out of 60) were allergic to latex (specific IgE >0.7 kU/l and clinical manifestations). The principal factor correlated with allergy to latex was specific serum IgE to latex (radioallergosorbent test [RAST]) values (p<0.01). Other factors were total serum IgE (paper radioimmunosorbent test [PRIST]) values, number of surgical procedures and familiarity with allergy. CONCLUSION: These results underline the importance of prophylactic measures to avoid the exposure, not only in the sanitary environment, through the institution of latex-safe routes, but also in daily life, to prevent potentially serious allergic reactions.

Myelomeningocele, avocados, and rubber tree plants.

Infants with myelomeningocele and the nurses who care for them have something in common. Both are at higher risk than the general population for developing latex allergies. This article provides a review of the literature regarding latex production, latex allergic responses in children and adults, types of latex allergic reactions, and prevention of latex allergies.

The immunohistochemical profile of the myelomeningocele placode: is the placode normal?

One key to predicting optimal outcome of novel treatments, such as fetal surgery, for myelomeningocele is understanding the structure of the placode. We hypothesize that if the placode retains normal patterning and is simply unneurulated, then repair may be effective in preventing secondary injury. Serial sections of human myelomeningocele placodes were characterized using novel immunohistochemical caudal spinal cord markers (H4C4, AC4, NOT, VIN-IS-53, and FP3) and established structural markers (e.g. neurofilament, glial fibrillary acidic protein, or synaptophysin). The myelomeningocele placodes studied exhibited abnormal patterning along the dorsoventral and rostrocaudal axes indicative of a change in pattern determination and a paucity of maturing neurons. In addition, there was significant inflammatory infiltrate, gliosis and fibrosis consistent with secondary injury. Additionally, injury to the placode was also demonstrated. The combination of effects may be contributory to abnormal spinal cord function in myelomeningocele patients.

Current management of the infant with myelomeningocele.

Infants with myelomeningocele continue to be a management dilemma for urologists. This article discusses many of the current questions that surround the newborn with myelomeningocele. What radiologic studies should be performed and when? How does the clinician determine if bladder drainage is adequate or requires altering? If a problem is identified what are the surgical options? When should urodynamics be performed? Ultimately how one manages, follows and initiates treatments in the newborn will have a significant effect on the long-term morbidity seen in this population of children.

Latex allergy and latex sensitization in children and adolescents with meningomyelocele.

BACKGROUND: The high prevalence of clinical latex allergy and latex sensitization in children with meningomyelocele has been widely reported. It has also been noted that these same children have a higher than expected prevalence of atopic disease. It would be useful to have a safe, sensitive, and specific skin test to detect latex sensitivity and to know how well this test compares with available in vitro tests. It would likewise be helpful to know as fully as possible the characteristics of the individual and to evaluate the relative importance of factors suspected to contribute to clinical latex allergy and latex sensitization in this population. METHODS: A group of 116 children and adolescents 1 to 20 years of age were recruited for the study. An extensive history of latex allergy, atopic diseases, and surgical procedures was taken on all subjects. Each subject had either a latex skin test or an in vitro study for latex-specific IgE, and 67 subjects had both tests simultaneously. Eighty-five subjects had epicutaneous skin tests to a panel of environmental allergens. RESULTS: Overall, 25 of 116 (21.5%) subjects had a history of clinical latex allergy, and 51 of 116 (44%) were sensitized to latex. The sensitivity and specificity of skin tests for clinical latex allergy were slightly greater than for the in vitro test (100% vs 95.8% and 82.3% vs 68.9%, respectively). The positive predictive value and negative predictive value of skin testing for clinical latex allergy were also greater (67.6% vs 50% and 100% vs 98.1%, respectively). Age was found to be a significant variable for both latex allergy and latex sensitization. The number of surgical procedures undergone and the presence of positive skin test responses to environmental allergens were significantly correlated with latex sensitization but not with clinical allergy to latex. CONCLUSIONS: A sensitive, specific, and safe skin test for latex sensitivity appears superior to in vitro testing for latex allergy. Age, number of surgical procedures, and the presence of positive allergen skin test responses are significantly correlated with latex sensitization. Age alone is significantly correlated with clinical allergy to latex.

Latex allergy in children with spina bifida.

We studied the prevalence of latex-specific IgE among the children in our myelomeningocele clinic and several groups of controls using skin tests, a commercially available ELISA and an in-house RAST. Thirty-nine of 83 (47%) children with myelomeningocele had antibodies directed against latex as did 6 of 40 (15.7%) chronically ill controls, 4 of 105 (3.8%) medical controls and 2 of 75 (2.7%) well controls. Within each study group the likelihood of a positive skin test increased with the number of operations the subject had undergone. Children with myelomeningocele were much more likely to have antibodies to latex than were chronically ill controls with similar surgical histories. A retrospective chart review of 18 years and a total of 646 operations disclosed only one episode of intraoperative anaphylaxis which appeared to be related to latex within our study group.

Alergia al latex en un niño con mielomeningocele / Allergy to latex in a child with menningomyelocele

De acuerdo con los datos de la bibliografía Internacional los pacientes con mielomeningocele se deben considerar como de alto riesgo para desarrollar alergia al látex. En este trabajo describimos el primer caso de alergia al látex, mediada por IgE, en un niño en Argentina y comentamos los resultados preliminares obtenidos en la población con MMC del Hospital de Niños Ricardo Gutierrez

Alergia al latex en un niño con mielomeningocele / Allergy to latex in a child with menningomyelocele

De acuerdo con los datos de la bibliografía Internacional los pacientes con mielomeningocele se deben considerar como de alto riesgo para desarrollar alergia al látex. En este trabajo describimos el primer caso de alergia al látex, mediada por IgE, en un niño en Argentina y comentamos los resultados preliminares obtenidos en la población con MMC del Hospital de Niños Ricardo Gutierrez

Characterization of latex antigen and demonstration of latex-specific antibodies by enzyme-linked immunosorbent assay in patients with latex hypersensitivity.

Two latex antigens, one extracted from surgical gloves (GE) and the other from the sap of Hevea brasiliensis plant (RPE) were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis. These antigens were used to detect latex specific IgE and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) in the sera of patients with meningomyelocele (spina bifida) and of normal controls. Of the 36 patients studied, 26 had wheal-and-flare skin-prick test reactivity to latex antigen with 11/26 having had a history of anaphylaxis to latex products. Twenty three of the 26 sera from skin-test positive patients and 10/11 patients with history of anaphylaxis demonstrated significant levels of latex specific IgE and IgG in the sera, whereas only 1/14 normals showed significant antibodies to latex. The remaining 10 patients, all skin-test negative with latex antigens, showed only low levels of antibodies. The findings indicate that the ELISA used in the present study employing partially characterized antigens has sensitivity and specificity to detect latex specific antibodies in the sera of suspected patients and can be used for presumptive diagnosis of latex allergy.

Evaluation of latex allergy in patients with meningomyelocele.

Seventy-six patients with meningomyelocele were evaluated for latex sensitivity by medical history and epicutaneous skin testing. Four different latex glove extracts, two nonlatex glove extracts, cornstarch, selected inhalant antigens, and negative and positive controls were used for skin testing. Forty-nine patients (64.5%) were skin test positive to latex extracts (latex-positive group). Twenty-four patients (49%) of the latex-positive group and none of the latex-negative group had histories of immediate reactions to latex products (P less than .001). The latex-positive group had a higher mean number of surgical procedures, 12.67 +/- 11.27, compared with 6.89 +/- 6.55 (P less than .001) in the latex-negative group. Twenty-three of the latex-positive patients (47%) used latex products daily compared to seven patients (26%) in the latex-negative group (P = .073). Twenty latex-positive patients (41%) had atopy compared with five patients (19%) of the latex negative group (P = .041). There was no significant difference between the two groups in age, sex, daily catheterization, or positive skin tests to cornstarch. All 76 patients tested negative to the nonlatex glove extracts. Ten control subjects tested negative for all latex and nonlatex glove extracts.

Determination of amniotic fluid IgM and IgA by hydroxyethylcellulose-agarose gel electroimmunodiffusion.

An electroimmunodiffusion method on hydroxyethylcellulose-agarose by which IgA and IgM concentrations down to 0.3 mg/dl can be measured in amniotic fluid is presented. Elevated Ig levels were found in both fetal infection and in congenital malformations. The potential value of Ig determination in amniotic fluid is discussed.