Isotonic saline in children with perennial allergic rhinitis.

Children with HDM allergy suffer from perennial allergic rhinitis (PAR). The present pilot study evaluated nasal lavage with isotonic saline (0.9%) in 25 children (mean age 8.9 years; 13 males) with HDM-dependent PAR, assessing: nasal symptoms severity and parental perception of rhinitis control, sleep, and school performance. Nasal symptoms, rated by total symptom score, parental perception of PER control, sleep quality, and school performance, measured by visual analogue scale, were significantly improved by nasal lavage (p < 0.001) after treatment. The effects tended to persist also during the follow-up. In conclusion, the present pilot study provides the first evidence that nasal lavage with isotonic saline relieved the nasal symptoms of children with PAR and improved the parental perception of the disease.

Hypertonic saline monotherapy in children with perennial allergic rhinitis: a pilot study.

Perennial allergic rhinitis (PAR) is very common in children and has a relevant impact on their families. House dust mites (HDM) are the most relevant cause of PAR. The present pilot study aimed to evaluate whether hypertonic saline (3%) nasal spray as monotherapy is able to improve: nasal symptom severity and parental perception of rhinitis control, sleep, and school performance in HDM-mono-sensitized children with PAR. Globally, 25 children (13 males and 12 females; mean age 9.5±3.1 years) were treated for 3 weeks. They were visited at baseline, at the end of treatment, and after a 2-week follow-up. Hypertonic saline significantly reduced total symptom score, and improved the perception, according to their parents, of rhinitis control, sleep, and school performance. In conclusion, the present pilot study provided the first evidence that 3% hypertonic saline monotherapy was able to relieve nasal symptoms and parental perception of PAR impact as well as being safe and well tolerated.

Prolongation of cardiac allograft survival by a novel population of autologous CD117+ bone marrow-derived progenitor cells.

Autologous CD117(+) progenitor cells (PC) have been successfully utilized in myocardial infarction and ischemic injury, potentially through the replacement/repair of damaged vascular endothelium. To date, such cells have not been used to enhance solid organ transplant outcome. In this study, we determined whether autologous bone marrow-derived CD117(+) PC could benefit cardiac allograft survival, possibly by replacing donor vascular cells. Autologous, positively selected CD117(+) PC were administered posttransplantation and allografts were assessed for acute rejection. Although significant generation of recipient vascular cell chimerism was not observed, transferred PC disseminated both to the allograft and to peripheral lymphoid tissues and facilitated a significant, dose-dependent prolongation of allograft survival. While CD117(+) PC dramatically inhibited alloreactive T cell proliferation in vitro, this property did not differ from nonprotective CD117(-) bone marrow populations. In vivo, CD117(+) PC did not significantly inhibit T cell alloreactivity or increase peripheral regulatory T cell numbers. Thus, rather than inhibiting adaptive immunity to the allograft, CD117(+) PC may play a cytoprotective role in prolonging graft survival. Importantly, autologous CD117(+) PC appear to be distinct from bone marrow-derived mesenchymal stem cells (MSC) previously used to prolong allograft survival. As such, autologous CD117(+) PC represent a novel cellular therapy for promoting allograft survival.

Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.

The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established. Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection. However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown. The purpose of this study was to determine whether islet allografts and/or rat islet xenografts required host CD80/CD86 molecules for acute rejection. Streptozotocin-induced diabetic C57Bl/6 (B6, H-2(b)) or B6 CD80/CD86 double-deficient mice were grafted with allogeneic BALB/c (H-2(d)) islet allografts or with WF (RT1(u)) islet xenografts. Nondiabetic B6 mice were grafted with BALB/c heterotopic cardiac allografts. Consistent with previous reports, BALB/c islet allografts were acutely rejected in wild-type B6 mice could survive long-term (>100 days) in B6 CD80/CD86-deficient animals. In stark contrast, both islet allografts and WF rat islet xenografts demonstrated acute rejection in both control B6 and in B6 CD80/CD86 deficient hosts. In conclusion, varied studies imply that the inherent pathways for rejecting primarily vascularized versus cellular allografts or xenografts may be distinct. The present study illustrates this concept by showing a marked difference in the role of host-derived CD80/CD86 costimulatory molecules for cardiac allograft versus islet allograft/xenograft rejection in vivo. Although such costimulation is rate limiting for cardiac allograft rejection, these same molecules are not necessary for acute rejection of either islet allografts or xenografts.

Improved pretransplant management of infants with hypoplastic left heart syndrome enables discharge to home while waiting for transplantation.

For infants whose families select primary transplantation for hypoplastic left heart syndrome (HLHS), the waiting time averages 3 months. Given the relative shortage of organs, the morbidity and mortality of these patients have been high. Therefore, pretransplant management is critical to improve the number of patients who survive to transplantation. This series shows our evolving management for these children, with an emphasis on nonintensive care. Fifty-two infants with HLHS were listed for primary transplantation at our institution during a 6-year period. The management was aimed at manipulating the pulmonary and systemic blood flows by low-dose continuous infusion of prostaglandin E1 (PGE1), early use of inhaled nitrogen, delayed opening of the atrial septum, and discharge to home with PGE1 infusion for continuing care when the child was on room air and growing. Almost all of the children (46/ 52) required nitrogen therapy with initial FiO2 of 0.16-0.17. Patients were weaned off nitrogen by 5 to 6 weeks of age. One fourth of the children needed atrial septal opening, typically at 2 or 3 months of age. Seventeen (32.7%) of the infants were able to spend at least some of their waiting time at home. Forty-five of the 52 children (86.5%) survived to receipt of a donor heart. Newborns with HLHS whose families select primary transplantation as their surgical option can be managed with a minimally invasive approach until receipt of a donor heart with an improvement in mortality rate.

Acoso moral (mobbing): un nuevo riesgo en la medicina del trabajo / Moral harassment: a new risk in occupational medicine

Los riesgos psicosociales se están constituyendo en una de las principales causas de alteración de la salud en los puestos de trabajo. En los últimos años, el "riesgo relacional o interpersonal" - mobbing - se ha ido incrementando debido a los cambios macroeconómicos y por el cambio en la tipología del trabajo y en los riesgos laborales derivados. Cada trabajador, independientemente de las características de su propia personalidad y del propio carácter, puede ser objeto de acoso moral. Los primeros efectos derivados del mobbing son observables sobre la salud de la víctima que, casi siempre, después de un intervalo variable, se altera con manifestaciones en la esfera neuropsíquica, Las consecuancias sociales pueden ser devastadoras. El costo del mobbing no se limita a los aspectos individuales, sino que se refleja generalmente a nivel de la empresa. La gestión del fenómeno de mobbing es multidisciplinaria. A nivel asistencial, el rol del médico del trabajo, del psiquiatra y del psicólogo son interdependientes y deben por lo tanto ser integrados en una estructura funcional unitaria...

Acoso moral (mobbing): un nuevo riesgo en la medicina del trabajo / Moral harassment: a new risk in occupational medicine

Los riesgos psicosociales se están constituyendo en una de las principales causas de alteración de la salud en los puestos de trabajo. En los últimos años, el "riesgo relacional o interpersonal" - mobbing - se ha ido incrementando debido a los cambios macroeconómicos y por el cambio en la tipología del trabajo y en los riesgos laborales derivados. Cada trabajador, independientemente de las características de su propia personalidad y del propio carácter, puede ser objeto de acoso moral. Los primeros efectos derivados del mobbing son observables sobre la salud de la víctima que, casi siempre, después de un intervalo variable, se altera con manifestaciones en la esfera neuropsíquica, Las consecuancias sociales pueden ser devastadoras. El costo del mobbing no se limita a los aspectos individuales, sino que se refleja generalmente a nivel de la empresa. La gestión del fenómeno de mobbing es multidisciplinaria. A nivel asistencial, el rol del médico del trabajo, del psiquiatra y del psicólogo son interdependientes y deben por lo tanto ser integrados en una estructura funcional unitaria...(AU)

Mycophenolic acid levels in pediatric heart transplant recipients receiving mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil (MMF) is an immunosuppressive agent that has shown promise in adult patients who have undergone heart transplantation. There have been a number of studies of the pharmacokinetics of MMF in adult solid organ transplant recipients, but there is very little information in the pediatric population. The purpose of this study was to review our experience with MMF dosing and the role of mycophenolic acid (MPA) levels for therapeutic drug monitoring in a population of pediatric heart transplant recipients. METHODS: Data were obtained by review of the pediatric heart transplant database between November 1, 1997 and October 15, 1998. The data included all serum trough MPA levels, patient age, weight, height, indication for and dose of MMF, other medications, and details of all episodes of graft rejection. RESULTS: Forty-four patients (27 males) had a total of 128 serum trough MPA levels. Median age at transplant was 2.7 years (7 days to 18.4 years), and at time of review was 6.3 years (29 days to 23.5 years). MMF treatment was used for induction in 18 patients, induction and rejection in 23 patients and graft vasculopathy in 3 patients. Dosing by body surface area (mg/m(2)), age and interval from transplantation were all independently associated with MPA level. There was a trend toward requiring higher doses to achieve desired levels (>3 ng/ml) in younger patients. The average dose to achieve desired levels was higher in the immediate post-transplant period. There was a trend that MPA levels for a given dose were higher in patients on concurrent tacrolimus therapy. CONCLUSIONS: (1) There is marked individual variation in pharmacokinetics of MMF in pediatric patients; (2) dosing by body surface area may be advantageous; (3) higher MMF doses may be required at younger ages and in the early period after transplantation; (4) lower MMF doses may be required with concurrent tacrolimus therapy; and (5) serum trough MPA levels may relate to efficacy. Therefore, therapeutic drug monitoring of serum trough MPA levels may be required for individualized MMF dosing in pediatric cases.

Donor IFN-gamma receptors are critical for acute CD4(+) T cell-mediated cardiac allograft rejection.

Recent studies using mouse models demonstrate that CD4(+) T cells are sufficient to mediate acute cardiac allograft rejection in the absence of CD8(+) T cells and B cells. However, the mechanistic basis of CD4-mediated rejection is unclear. One potential mechanism of CD4-mediated rejection is via elaboration of proinflammatory cytokines such as IFN-gamma. To determine whether IFN-gamma is a critical cytokine in CD4-mediated acute cardiac allograft rejection, we studied whether the expression of IFN-gamma receptors on the donor heart was required for CD4-mediated rejection. To investigate this possibility, purified CD4(+) T cells were transferred into immune-deficient mice bearing heterotopic cardiac allografts from IFN-gamma receptor-deficient (GRKO) donors. While CD4(+) T cells triggered acute rejection of wild-type heart allografts, they failed to trigger rejection of GRKO heart allografts. The impairment in CD4-mediated rejection of GRKO hearts appeared to primarily involve the efferent phase of the immune response. This conclusion was based on the findings that GRKO stimulator cells provoked normal CD4 proliferation in vitro and that intentional in vivo challenge of CD4 cells with wild-type donor APC or the adoptive transfer of in vitro primed CD4 T cells failed to provoke acute rejection of GRKO allografts. In contrast, unseparated lymph node cells acutely rejected both GRKO and wild-type hearts with similar time courses, illustrating the existence of both IFN-gamma-dependent and IFN-gamma-independent mechanisms of acute allograft rejection.

Erythrocyte sedimentation rate and C-reactive protein discrepancy and high prevalence of coronary artery abnormalities in Kawasaki disease.

BACKGROUND: An outbreak of Kawasaki disease (KD) in Colorado between November, 1997, and June, 1998, provided the opportunity to study inflammatory indices and coronary artery abnormalities. METHODS: Medical records of the 33 patients diagnosed with KD at The Children's Hospital during the outbreak were reviewed. Demographic and clinical information, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and echocardiogram results were recorded. Traditional abnormalities (dilatation, aneurysm, ectasia), as well as "prominence" of the coronary arteries were noted. RESULTS: Twenty-five patients had CRP and ESR performed on the day of admission; 11 of 25 (44%) had a discrepancy between the height of the ESR and CRP values (high ESR and low CRP or low ESR and high CRP). The mean CRP was higher in patients who presented in <10 days than in patients who presented in > or =10 days: 13.9 mg/dl vs. 5.2 mg/dl (P = 0.01). The ESR value did not correlate with the day of illness. Age, gender or presence of coronary artery abnormalities did not correlate with the height of CRP or ESR elevation. Thirty percent of patients had at least one abnormality on their initial echocardiogram (dilatation, aneurysm, ectasia). An additional 24% of patients displayed prominence as the only finding on their initial echocardiogram. Of the 33 patients 7 (21.2%) had coronary artery aneurysms. CONCLUSIONS: Many patients with KD have discrepancies in the degree of elevation of CRP and ESR. Physicians should consider obtaining both tests in patients with KD. This outbreak was associated with a high degree of coronary artery abnormalities. The finding of coronary artery prominence is an observation that deserves further study.

Immunobiology of cardiac allograft and xenograft transplantation.

Heart transplantation has been performed clinically for four decades, and has become the standard of care for end-stage heart disease. Our understanding of the immunobiology of transplantation has made tremendous strides, but our knowledge still lags behind the clinical use. As a result, nonspecific immunosuppression remains the standard therapy. This chapter is a review of our present knowledge of the immunobiology of allotransplantation and xenotransplantation with emphasis on antigen presentation, costimulation, and T-cell activation in the context of transplantation. The molecular events of T-cell activation, with some emphasis on the sites of action of present day immunosuppression, are reviewed. Basic aspects of immunosuppression are reviewed elsewhere in this edition. Given the paucity of allografts, xenografts are being considered as an alternative donor source. This being the case, cellular and humoral response to xenografts is considered and contrasted with our understanding of allograft immunity. Basic mechanisms of tolerance are discussed, with examples of experimental tolerance induction in small and large animals. A brief description of special considerations for the immunology in human neonate/infant recipients is mentioned. Understanding the immunobiology of transplantation is key to making decisions regarding heart transplant recipients today, in addition to developing better protocols and the induction of tolerance in the future.

CD4 T cell-mediated cardiac allograft rejection requires donor but not host MHC class II.

Numerous studies indicate that CD4 T cells are required for acute cardiac allograft rejection. However, the precise role for CD4 T cells in this response has remained ambiguous owing to the multipotential properties of this T-cell subpopulation. In the current study, we demonstrate the capacity of CD4 T cells to serve as direct effector cells of cardiac allograft rejection. We show that CD4 T cells are both necessary and sufficient for acute graft rejection, as indicated by adoptive transfer experiments in immune-deficient SCID and rag1(-/-) recipients. We have analyzed the contribution of direct (donor MHC class II restricted) and indirect (host MHC class II restricted) antigen recognition in CD4-mediated rejection. Acute CD4 T cell-mediated rejection required MHC class II expression by the allograft, indicating the importance of direct graft recognition. In contrast, reciprocal experiments indicate that CD4 T cells can acutely reject allogeneic cardiac allografts established in rag1(-/-) hosts that were also MHC class II deficient. This latter result indicates that indirect presentation of donor antigens by host MHC class II is not required for acute CD4-mediated rejection. Taken together, these results indicate that CD4 T cells can serve as effector cells for primary acute cardiac allograft rejection, predominantly via direct donor antigen recognition and independent of indirect reactivity.

Heart transplantation in children: indications. Report of the Ad Hoc Subcommittee of the Pediatric Committee of the American Society of Transplantation (AST).

This review details the indications for heart transplantation in children. Contraindications have evolved from absolute to relative. Controversial issues remain and this paper represents a consensus of more than a dozen centers that have programs that remain active performing pediatric heart transplants.

Anti-human cardiac myosin autoantibodies in Kawasaki syndrome.

Kawasaki syndrome (KS) is the major cause of acquired heart disease in children. Although acute myocarditis is observed in most patients with KS, its pathogenesis is unknown. Because antimyosin autoantibodies are present in autoimmune myocarditis and rheumatic carditis, the purpose of the current study was to determine whether anticardiac myosin Abs might be present during the acute stage of KS. Sera from KS patients as well as age-matched febrile controls and normal adults were compared for reactivity with human cardiac myosin in ELISAs and Western blot assays. A total of 5 of 13 KS sera, as compared with 5 of 8 acute rheumatic fever sera, contained Ab titers to human cardiac myosin that were significantly higher than those found in control sera. Both cardiac and skeletal myosins were recognized in the ELISA by KS sera, although stronger reactivity was observed to human cardiac myosin. Only IgM antimyosin Abs from KS sera were significantly elevated relative to control sera. KS sera containing antimyosin Abs recognized synthetic peptides from the light meromyosin region of the human cardiac myosin molecule and had a different pattern of reactivity than acute rheumatic fever sera, further supporting the association of antimyosin Ab with KS. These Abs may contribute to the pathogenesis of acute myocarditis found in patients with KS.

Infant heart transplantation: improved intermediate results.

OBJECTIVES: Our objectives were to (1) review our experience with heart transplants in infants (age < 6 months), (2) delineate risk factors for 30-day mortality, and (3) compare outcomes between our early and recent experience. METHODS: Records of all infants listed for transplantation in our center before September 1996 were analyzed. Early and recent comparisons were made between chronologic halves of the accrual period. Univariate analysis was used to analyze potential risk factors for 30-day mortality (categorical variables, Fisher's exact test; continuous variables, nonparametric Wilcoxon rank-sum test). Multivariable analysis included univariate variables with p values < or = 0.10. Actuarial survivals were estimated (Kaplan-Meier) and compared by the log-rank test. RESULTS: Fifty-one of the 60 infants listed for transplantation were operated on (waiting list mortality 15%). Thirty-day mortality was 18% overall, 30% in the first 3 years and 10% in the last 3 years (p = 0.07). Sepsis was the commonest cause of early death (4/9). Univariate analysis suggested four potential risk factors for early death: preoperative mechanical ventilation (p = 0.01), prior sternotomy (p = 0.002), preoperative inotropic drugs (p = 0.08), and warm ischemia time (p = 0.08). Multivariable analysis indicated that prior sternotomy (p = 0.01) was an independent risk factor for 30-day mortality. Actuarial survivals were 80%, 78%, and 70% at 1, 2, and 3 years, and these figures improved between early and recent groups (p = 0.05). Late deaths were most commonly due to acute rejection (3/5). CONCLUSIONS: Results of heart transplantation in infancy improve with experience. Prior sternotomy increases initial risk. Intermediate-term survival for infants with end-stage heart disease is excellent.