Specific patterns of CD4-associated immunosenescence in vertically HIV-infected subjects.

Vertical transmission of human immunodeficiency virus (HIV) represents an important world-wide health problem although the incidence in developed countries has been drastically reduced by the extensive use of highly active antiretroviral therapy. Vertically HIV-infected subjects have been exposed to the virus during the maturation of their immune systems and have suffered a persistent chronic activation throughout their lifetime; the consequences of this situation for their immune system are not fully understood. The objective of this study was to analyse immunosenescence-related parameters in different CD4 T-cell subsets. Fifty-seven vertically HIV-infected subjects and 32 age-matched healthy subjects were studied. Activation (HLA(-) DR(+) ), senescence (CD28(-) CD57(+) ) and proliferation (Ki67(+) ) were analysed on different CD4 T-cell subsets: naive (CD45RA(+) CD27(+) ), memory (CD45RO(+) CD27(+) ), effector memory (CD45RO(+) CD27(-) ) and effector memory RA (CD45RA(+) CD27(-) ). Compared with healthy subjects, vertically HIV-infected subjects showed increased naive and memory CD4 T-cell frequencies (p 0.035 and p 0.010, respectively) but similar frequencies of both effector subsets. Whereas naive CD4 T cells were not further altered, memory CD4 T cells presented increased levels of senescence and proliferation markers (p <0.001), effector memory CD4 T cells presented increased levels of activation, senescence and proliferation markers (p <0.001) and effector memory RA CD4 T cells presented increased levels of activation and senescence (p <0.001) compared with healthy subjects. Despite long periods of infection, vertically HIV-infected subjects show specific patterns of immunosenescence, revealing a preserved CD4 T-cell homeostasis for subset differentiation and distribution. Nevertheless, excepting the naive subpopulation, all subsets experienced some immunosenescence, pointing to uncertain consequences of the future aging process in these subjects.

Short communication: evaluation of the effect of enfuvirtide in 11 HIV-1 vertically infected pediatric patients outside clinical trials.

The effect of enfuvirtide (ENF) in 11 HIV-1 heavily antiretroviral-experienced children and adolescents enrolled in the HIV-1 Paediatric Spanish cohort was further investigated. Patients who received ENF with novel drugs (etravirine, darunavir, and/or tipranavir) reached and maintained undetectable plasma HIV-1 RNA levels and showed immunological recovery within the first 3 months of therapy that was maintained during the follow-up. Viremia was not fully suppressed in patients who did not combine ENF with novel drugs but interestingly, immunological benefit was observed in half of these patients. Therefore, ENF showed a greater and more stable efficacy when administrated with novel drugs.

Enzyme replacement therapy with agalsidase alfa in children with Fabry disease.

AIM: To assess the effects of enzyme replacement therapy (ERT) in children with Fabry disease. METHODS: Safety and efficacy of ERT with agalsidase alfa, 0.2 mg/kg infused over 40 minutes every 2 weeks for 23 weeks, were studied in a multicentre open-label trial in nine boys and four girls. Median age at the start of the study was 11.0 years (range 3.5-18 years). RESULTS: Fifty-four adverse events were reported in 11 patients. No serious adverse events related to ERT were reported. Twelve of the 54 adverse events were considered possibly or probably related to ERT. Infusion reactions (8 mild, 3 moderate) occurred in four boys, in seven infusions. One boy developed IgG antibodies, although he continued to make good clinical progress. At the end of the study, two of the four boys and the one girl on regular pain medication at baseline had stopped taking analgesics. Brief Pain Inventory (BPI) scores decreased in most patients by week 12 and were sustained until the end of the study. This change was greater in the boys, who had higher (worse) BPI scores at baseline. Pain-related quality of life (QoL) scores also decreased during the study. Plasma globotriaosylceramide concentrations and urinary globotriaosylceramide:sphingomyelin ratios decreased after 12 and 23 weeks of therapy, particularly in the boys. Increases in sweat volume were recorded in three out of five of the boys and in one of two girls tested after 23 weeks of treatment. CONCLUSION: ERT with agalsidase alfa in children with Fabry disease is well tolerated and, in the short term, appears to decrease pain and to improve pain-related QoL.

Linfohistiocitosis hemofagocítica (I) / Hemophagocytic lymphohistiocytosis

La linfohistiocitosis hemofagocítica (LHH) es una enfermedad rara con una alta morbimortalidad. Se caracteriza por una disfunción de las células efectoras del sistema inmunológico, que puede ser debida a un defecto congénito o adquirido. Clínicamente, presenta un cuadro de fiebre, hepatosplenomegalia y síntomas neurológicos. A nivel de parámetros analíticos, observamos citopenias, alteración en la coagulación, cambios en el perfil lipídico, elevación de citocinas inflamatorias, e infiltración de órganos por histiocitos y fenómenos de hemofagocitosis. Recientemente, se ha detectado un defecto a nivel de células inmunes efectoras, caracterizado por la ausencia de la actividad natural killer (NK). El tratamiento inicial debe ir encaminado a la supresión del ambiente de hiperinflamación presente en estos niños; el trasplante de medula ósea es el tratamiento de elección en los casos de LHH congénita. En la actualidad, los enfermos de LHH pueden beneficiarse de nuevas técnicas diagnósticas específicas y mejores medidas terapéuticas (AU)

[T-cell subsets variation during clinical and immunological progression in vertically HIV-infected children]. / Variacion de las subpoblaciones de células T según la progresión clínica e inmunológica en niños infectados verticalmente por HIV-1.

We have investigated the relationship among peripheral blood T-cell subsets with immunological and clinical categories, and viral load (VL) in 65 HIV-1-infected children on stable antiretroviral therapy (ART): 26 (40%) children on combination therapy with 2 nucleoside inhibitors, and 39 (60%) children on highly active antiretroviral therapy (HAART). T-cell subsets were determined by flow cytometry. VL was quantified using a standardized molecular method. Naïve CD4+ T-cells (CD45RA+CD62L+) were lower in children with low %CD4+ T-cells, but neither in children with advanced stage of illness nor with high VL. By contrast, naïve CD8+ T-cells were lower in children with low %CD4+ T-cells, advanced stage of illness and high VL. Memory (CD45RO+) and activated (CD38+, HLA-DR+ and CD38+HLA-DR+) CD4+ and CD8+ T-cells were higher in children with low %CD4+ T-cells, advanced stage of illness and high VL. However, CD4+CD38+ T-cells were higher in HIV-children with CD4+ > 25% than in the control group (p < 0.001) and were diminished in children with low %CD4+ T-cells. Naïve and memory CD4+ and CD8+ T-cells are more tightly dependent on the immunological category than on clinical category or plasma VL. Furthermore, our data indicate an association between low %CD4+ T-cells, high VL and high expression of cellular activation markers, although not with advanced clinical stage, possibly due to ART.

Variacion de las subpoblaciones de células T según la progresión clínica e inmunológica en niños infectados verticalmente por HIV-1. / [T-cell subsets variation during clinical and immunological progression in vertically HIV-infected children]

We have investigated the relationship among peripheral blood T-cell subsets with immunological and clinical categories, and viral load (VL) in 65 HIV-1-infected children on stable antiretroviral therapy (ART): 26 (40

) children on combination therapy with 2 nucleoside inhibitors, and 39 (60

) children on highly active antiretroviral therapy (HAART). T-cell subsets were determined by flow cytometry. VL was quantified using a standardized molecular method. Na´ve CD4+ T-cells (CD45RA+CD62L+) were lower in children with low

CD4+ T-cells, but neither in children with advanced stage of illness nor with high VL. By contrast, na´ve CD8+ T-cells were lower in children with low

CD4+ T-cells, advanced stage of illness and high VL. Memory (CD45RO+) and activated (CD38+, HLA-DR+ and CD38+HLA-DR+) CD4+ and CD8+ T-cells were higher in children with low

CD4+ T-cells, advanced stage of illness and high VL. However, CD4+CD38+ T-cells were higher in HIV-children with CD4+ > 25

than in the control group (p < 0.001) and were diminished in children with low

CD4+ T-cells. Na´ve and memory CD4+ and CD8+ T-cells are more tightly dependent on the immunological category than on clinical category or plasma VL. Furthermore, our data indicate an association between low

CD4+ T-cells, high VL and high expression of cellular activation markers, although not with advanced clinical stage, possibly due to ART.

Infecciones oportunistas en pacientes pediátricos con infección por VIH / Opportunistic infections in HIV-infected children

Desde que comenzaron a describirse los primeros casos de SIDA en 1981, las infecciones oportunistas ocuparon un papel importante en la morbilidad y en la mortalidad de los pacientes con infección por el VIH. Estudios epidemiológicos realizados en adultos demuestran que desde la introducción de los regímenes antirretrovirales potentes, la incidencia de episodios oportunistas ha disminuido considerablemente y, por tanto, se cuestiona el papel de la profilaxis en pacientes con infección por VIH en quienes se ha conseguido una respuesta antiviral adecuada. Sin embargo, el porcentaje de descenso no es el mismo para cada infección oportunista. En este trabajo se presenta una extensa revisión sobre cada uno de los microrganismos implicados en la incidencia de infecciones oportunistas (AU)

CD4+ and CD8+ T lymphocyte regeneration after anti-retroviral therapy in HIV-1-infected children and adult patients.

Previous studies have shown a slow recovery of naive CD4+ T cell counts after anti-retroviral therapy in HIV-1-infected adults, which is in accordance with thymus atrophy after puberty. Here we investigate whether or not different patterns of naive CD4+ and CD8+ T cell repopulation are present in adult and child patients undergoing anti-retroviral treatment. Thus, 25 adults under highly active anti-retroviral therapy and 10 children under combined anti-retroviral therapy were retrospectively analysed for T cell subpopulations at baseline (T0) and around week 12 (T1) and week 24 (T2) of anti-retroviral treatment. Mean serum HIV-1 RNA levels dropped in both groups. Recovery of T cells in adults was characterized by a heterogeneous response between patients, with only 44% of them increasing their naive CD4+ and CD8+ T cell counts at T1, and changes in mean total CD4+ T cells were mainly shaped by memory cells. Otherwise, children were characterized by an early increase in naive T cells. Thus, at T1, all children analysed had a strong rise in CD4+ (from 389 +/- 116 to 569 +/- 121 cells/microl; P < 0.01), and nine out of 10 also in naive CD8+ T cells (from 244 +/- 58 to 473 +/- 85 cells/microl; P < 0.05). However, no significant correlation between age and naive repopulation was observed (P = 0. 22) in children. Thus, children had the earlier and greater increases in naive T cell subsets than adults, probably due to a more active thymus, with the potential for immune reconstitution when HIV-1 replication is controlled.

[Clinico-radiological correlation of pulmonary complications of pediatric HIV infection]. / Correlación clínico-radiológica de las complicaciones pulmonares de la infección VIH en Pediatría.

Fifty-five percent of children with HIV infection, aged two months to ten years, were admitted at our hospitals because of respiratory conditions. Pulmonary complications found at admission in these children were lymphoid interstitial pneumonitis, Pneumocystis carinii pneumonia, fungal over-infection, tuberculosis, and bacterial complications. Also, non-specific infectious bronchial conditions, probably of viral origin. The most representative chest-X rays of these pulmonary conditions were analyzed; together with data from clinical records a clinico-radiological diagnosis was obtained.

[The surgical treatment of critical aortic stenosis in a child by the Ross-Konno technic]. / Tratamiento quirúrgico de la estenosis aórtica crítica en el niño mediante la técnica de Ross-Konno.

A twenty-nine-day old male infant suffering from critical aortic stenosis underwent aortic valvotomy by cardiopulmonary bypass. At three years of age the aortic stenosis recurred and the child underwent a balloon aortic valvuloplasty, but developed severe aortic insufficiency after the procedure. The critical condition of the patient made aortic valve replacement mandatory. The surgical technique consisted of aortoventriculoplasty with infundibular and valve pulmonary autograft for substituting the aortic root (Ross-Konno technique). As for as we know this is the first report on the Ross-Konno procedure in Spanish journals.

[Anatomic correction of transposition of great vessels with entire interventricular septum. Initial results]. / Corrección anatómica de la transposición de las grandes arterias con septo interventricular íntegro. Resultados iniciales.

INTRODUCTION: Optimal management for patients with simple transposition of great arteries is currently the arterial switch operation. We review our initial experience to evaluate the results. METHOD: From 1988 to 1993, 21 children with simple transposition of the great arteries underwent arterial switch operation. Mean age at surgery was 10.5 +/- 5.6 days, excluding two cases with two-stage arterial switch and one with late diagnosis. Patent ductus arteriosus was present in 12 cases, and a small ventricular septal defect in two. The coronary artery pattern was unusual in 9 cases. Balloon atrial septostomy was performed in 19 cases, seven of them using two-dimensional echocardiography. It was considered no necessary in the remaining two, with a large ductus arteriosus. RESULTS: Total circulatory arrest was used in 13 patients (mean time 29.7 +/- 22.6 min). Three patients died in the early postoperative period (14.3%) in a refractory cardiac failure, one of them secondary to myocardial necrosis. The coronary artery pattern was unusual in two of died patients. All patients but three were in sinus rythm. Mean age at follow-up was 21 months (follow-up range 2 months to 5 years). Seventeen of surviving patients are in a functional state grade I and one in grade II of NYHA. There haven't been late deaths. CONCLUSION: These results compared with the ones of atrial switch operation, have encouraged to us to use the arterial switch operation in all children with simple transposition of the great arteries. Increasing experience will likely lead to improve our results.

[The hypoplastic left heart syndrome. Initiation of a therapeutic program]. / Síndrome del corazón izquierdo hipoplásico. Iniciación de un programa terapéutico.

The hypoplastic left heart syndrome is a very severe congenital heart disease dependent on patency of ductus arteriosus in the newborn. The survival after neonatal period, without surgical treatment, is exceptional. Nowadays, there are basically two types of therapeutic procedures: Palliation with the Norwood operation and/or cardiac transplantation. Both methods have showed advantages and disadvantages; at present, there is not consensus of them. In our hospital, we have recently begun a medical-surgical therapeutic program for the management of neonates with hypoplastic left heart syndrome. Because of this, we report our little experience. We have treated three children in the last year: The first of them dead in the operating room; the second was exitus due to a sepsis two months after surgery, and the third, who is three-month-old now, remained well and was discharged to home.

[Children at risk. Our experience]. / Niños de riesgo. Nuestra experiencia.

Seventy children in a situation of risk, evaluated and treated in the Social Work Unit of the Children's Hospital "Virgen del Rocío" over a period of 22 months, were analyzed. Of these children, 89% corresponded to low-middle, low or very low social classes. The most common problems included those of the family (77.1%) with history of maltreatment and unwanted pregnancies being the most prevalent problems. In second place was the personal pathology of the parents (74.2%), with mental disorders and alcoholism being the main causes, followed by drug addiction and delinquency. Social factors (57.1%), which included predominantly unemployment and illiteracy, were the next most common finding. The final factor was the personal pathology of the child (10%). The consequences of the risk situation are described, emphasizing the psychic and treatment carried out. Final comments are made underlining the importance of awareness and professional training, multiprofessional teams, means of detecting and intervention into the problems, manpower and material as well as how to carry out studies in this area.

[Calcification of the intervertebral disk in children]. / Calcificación del disco intervertebral en el niño.

Authors present two cases of calcification of the intervertebral disc. They provide an analysis of etiology, symptoms, and roentgenographic clinic course, as well as a review of cases which have been reported in literature.