Short-term effects of growth hormone treatment on the upper airways of non severely obese children with Prader-Willi syndrome.

AIMS: The aim of this study was to establish whether short-term GH treatment causes obstructive apnea in patients with Prader-Willi syndrome and normal upper airway patency. SUBJECTS AND METHODS: We performed an observational longitudinal 6-week GH treatment study. Thirty-four non-severely obese Prader-Willi syndrome patients (20 boys, age range 0.94-11.8 yr, median 2.24 yr) entered an observational longitudinal 6-week study. Sixteen boys received recombinant human GH (rhGH) treatment; the remaining 18 represented the control group and received no treatment. Polysomnography monitoring and othorhinolaringoiatric video endoscopy were performed one night before and after 6 weeks of rhGH treatment (0.03 mg/kg body weight/day). All patients underwent auxologic assessment, fasting blood glucose, insulin and IGF-I evaluation. The main polysomnographic parameter considered was total apnea hypopnea index, consisting of two components: central apnea hypopnea index and obstructive apnea hypopnea index. All patients were free of severe or moderate upper airway obstruction when rhGH treatment began. RESULTS: After 6 weeks of rhGH therapy, obstructive apnea hypopnea index increased in 8/16 (50%), decreased in 5/16 (31%), and did not change in 3/16 (19%) patients. The changes were not statistically significant. The rhGH-treated group did not differ from the control group for the apnea hypopnea index both before and after 6 weeks of treatment. Adenoids and tonsils showed a slight increase in 1 and 2 patients on rhGH treatment, respectively, and did not change in the untreated patients. CONCLUSIONS: Our data show that short-term rhGH treatment does not cause restrictions of the upper airways in patients with Prader-Willi syndrome and normal upper airway patency.

Phenotype and function of dendritic cells and T-lymphocyte polarization in the human colonic mucosa and adenocarcinoma.

AIM: To evaluate the status of activation of the intestinal dendritic cells (DCs) and T lymphocytes (T cells) from surgical specimens of human colon and adenocarcinoma, and the potential effect of administration of interleukin 2 (IL-2). METHODS: Patients undergoing colectomy for cancer were randomized to receive subcutaneous IL-2 (12million UI/day) (treated group; n=10) for 3days before operation or no treatment (control group, n=10). DCs and T cells were isolated and purified from the lamina propria (LP) of segments of normal colon and adenocarcinoma of both groups. Cell phenotype was determined by expression of membrane receptors. Interaction between DC and T cells was assesses by a mixed leukocyte reaction using naïve T cells co-cultured with DCs. CD4+ T-cell polarization was studied by intracellular staining with monoclonal antibodies for interleukin-4 and interferon-gamma. RESULTS: CD4+ T cells were significantly less in tumour than in LP (p<0.05) in both treated and control groups. IL-2 did not modify the number of any of the T-cell subsets analysed. In contrast, T cells isolated from LP and neoplasm of treated patients produced more interferon-gamma and less interleukin-4 (p<0.05 vs. controls). IL-2 administration significantly increased (p<0.05) the number of mature, myeloid and plasmocytoid DCs compared to controls. Allogeneic naïve T cells were polarized toward a Th1 type of response which appeared to be mediated by IL-2 activated DCs. CONCLUSIONS: systemic IL-2 treatment may have immunomodulatory properties on intestinal DC maturation and drive a Th1 mediated anti-neoplastic response.

[Clinical role of interleukin-2 in the surgical treatment of liver metastasis due to colon adenocarcinoma]. / Ruolo clinico dell'interleuchina-2 nel trattamento chirurgico delle metastasi epatiche da adenocarcinoma del colon.

The surgical treatment of liver metastasis due to colorectal cancer can substantially modify the natural history of the disease, mainly when it is associated with effective medical treatment. Chemotherapy, via systemic or locoregional (intrahepatic) administration, has 2 possible objectives: as adjuvant treatment, to prevent or delay disease recurrence; as neo-adjuvant treatment, mainly interesting for the surgeon, to allow resective surgery in responding patients previously considered not-operable. Unfortunately, the severe immune deficiency associated with the advanced cancer negative impact on long-term outcome after any treatment (surgery, chemotherapy) is a limit for the clinical application of multidisciplinary treatments. Aim of this study is to review the possible different approaches to improve the clinical results, either as tumour response or overall survival, using an association of IL-2 with different chemotherapy procedures, in order to recover the locoregional and/or systemic immunodeficency. Several literature studies are worth of consideration not only for the biological activity reported, but also for the preliminary clinical results. At our Department, we have started a clinical experience in order to verify and confirm the results reported in these studies. The preliminary results seem to confirm an increase of chemotherapy activity obtained with an association of IL-2 immunotherapy with systemic therapy procedures and mainly with locoregional therapeutic programs.

[Nutritional therapy in surgical patients: an update]. / Terapia nutrizionale nei pazienti chirurgici. Un aggiornamento.

Patients undergoing major gastrointestinal surgery, often require an adequate artificial nutritional (AN) support for a pre-existing state of malnutrition and/or to overcome forced periods of postoperative starvation and/or for complications that alter the host metabolic response. When an indication to AN is given, enteral feeding should be preferred to parenteral nutrition because more physiological and less expensive. Moreover, recent data showed that patients fed enterally, rather than parenterally, in the postoperative period, have a significant better outcome with a reduction of morbidity and hospitalisation. The supplementation of standard feeds with key nutrients having immunomodulatory properties, such as arginine, omega-3 fatty acids and glutamine (pharmaconutrients), allows to control effectively the surgery-induced immunosuppression and hyperinflammation. An analysis on the principles of evidence-based medicine, supports the hypothesis that the pre-perioperative use of formulas enriched with pharmaconutrients, significantly reduces the rate of infectious complications and saves health care resources.

[Spontaneous pneumothorax caused by lung metastasis of sarcoma of the thigh]. / Pneumotorace spontaneo da metastasi polmonare di sarcoma della coscia.

Relapsing spontaneous pneumothorax can be the first manifestation of pulmonary metastases of soft tissues sarcomas. Standard imaging techniques and computed tomography may not be able to detect small malignant cystic lesion or to distinguish between them and benign bollous lesions. We report the case of a 33 year-old male who, in the past, underwent surgical treatment for a synovial sarcoma of the inferior limb. The patient was admitted to our hospital because of right spontaneous pneumothorax; both chest x-ray and CT scan didn't detect any metastatic pulmonary lesion. A few days after the discharge the patient was readmitted because of relapsed pneumothorax; high-definition CT of the chest revealed a pulmonary cystic lesion that was resected thoracoscopically. Histological examination revealed a pulmonary metastases of synovial sarcoma.

Immunological features of Down's syndrome: a review.

Young patients with Down's syndrome (DS) have high rates of infections, malignancies and autoimmune phenomena. Therefore, DS may be considered as a model of precocious, abnormal ageing of the thymus-dependent system in man. In DS children less than 6 years of age, the levels of serum immunoglobulins did not differ from healthy controls, but after that age, considerable hyper-IgG and -IgA were found. Furthermore, high levels of IgG1 and IgG3 have been found, whereas a progressive decline of IgG2 and IgG4 with age has been observed. The frequency of hepatitis B virus carriers even in the youngest age group is much higher among DS children. It has been reported that an IgG response was detectable in 75% of controls after HBsAg vaccination as compared to the 16.6% of DS patients. The presence of autoantibodies against human thyroglobulin did show a positive association with HB Virus Ag carriers, but only in the oldest DS subjects. Natural antibodies against intestinal antigens are low, while in the presence of cow's milk, abnormally high titres against casein and beta-lactoglobulin were present. High levels of IgG antibodies against gliadin have been observed. In spite of a normal percentage of CD3- and CD2-positive lymphocytes, a high proportion of cells express low-avidity receptors for sheep erythrocytes. Although the proportion of CD4+ T-lymphocyte helper-cells is normal, a marked imbalance in the CD4+ subpopulations has been documented. The percentage of suppressor-cytotoxic CD8+ lymphocytes is markedly increased. The responses to phytohemagglutinin and concanavalin A are within the normal range in the first decade of life and decline progressively thereafter. A recent study reported defective proliferative response to allo-mixed lymphocyte culture, with decreased expression of the membrane CD25, low secretion of interleukin 2 in the supernatant and depressed allo-specific cytotoxic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-phase proteins and levels of interleukin 1B, interleukin 6, tumor necrosis factor alpha, and interleukin 8 in children with pertussis.

OBJECTIVE: To determine serum levels of acute-phase proteins and interleukin 1B, interleukin 6, tumor necrosis factor alpha, and interleukin 8 in children with pertussis. DESIGN: Cross-sectional study. SETTING: Divisions of Infectious Diseases, Regional Hospital, and Pediatrics, University of Pavia, Varese, Italy. PARTICIPANTS: Eight children with pertussis, six with acute febrile infections, and eight healthy control children matched for sex, age, and time presentation over a 32-month study period. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: An immunoenzymatic assay was used to detect serum levels of all cytokines. Normal values of C-reactive protein, alpha 1-acid glycoprotein, and erythrocyte sedimentation rate were observed in the serum of patients with pertussis. The mean (+/- SD) detectable levels of tumor necrosis factor alpha (65.0 +/- 50.4 pg/mL) and interleukin 6 (32.3 +/- 17.8 pg/mL) were observed in the serum of patients with pertussis. In contrast, a nonsignificant increment of interleukin 1B levels (66.5 +/- 83.7 pg/mL) and interleukin 8 levels (12.7 +/- 17.8 pg/mL) was noted in the serum of the same patients. Increased and significant levels of all four cytokines were noted in most of the serum samples of patients with acute febrile infections. CONCLUSIONS: Acute-phase response is absent in patients with pertussis, whereas detectable and significant serum levels of tumor necrosis factor alpha and interleukin 6 were observed in some such patients.

Recombinant human erythropoietin is effective in correcting erythropoietin-deficient anaemia after allogeneic bone marrow transplantation.

Two children affected by severe aplastic anaemia (SAA) underwent allogeneic bone marrow transplantation (BMT) using partially matched family donors. In both cases there was a successful engraftment of donor haemopoietic stem cells. However, after an initial erythropoietic recovery, 5 months following BMT both children became severely anaemic. Although multiple factors were responsible for anaemia, in both cases there was a markedly impaired erythropoietin response to anaemia, as indicated by the inappropriately low levels of serum erythropoietin (EPO). Treatment with recombinant human erythropoietin (rHuEPO) induced a sustained erythropoietic response with complete correction of anaemia. This pilot study suggests that rHuEPO can be effective in correcting long-lasting anaemia after marrow transplantation, characterized by inadequate erythropoietin production.

From a historical outline of transplants to the concept of biological ego.

A chronology of the biological preliminaries of human transplantation science is proposed together with a chronological listing of the applications which transplants have had in clinical medicine in general and in pediatrics in particular. The most significantly immunological elements which surface from this assortment of experiences (in which those of pediatric interest have a considerable role) contribute easily to a more deeply perceived culture of man's biological individuality.

Analysis of X-chromosome inactivation and presumptive expression of the Wiskott-Aldrich syndrome (WAS) gene in hematopoietic cell lineages of a thrombocytopenic carrier female of WAS.

We report on a thrombocytopenic female belonging to a pedigree with the Wiskott-Aldrich syndrome (WAS). Restriction fragment length polymorphism (RFLP) analysis with probe M27 beta, closely linked to the WAS gene, demonstrated that she is a carrier of WAS. Both small-sized and normal-sized platelets were present, suggesting that, unlike the vast majority of WAS carriers, she does not manifest nonrandom X-chromosome inactivation in the thrombopoietic cell lineage. Study of X-chromosome inactivation by means of RFLP and methylation analysis demonstrated that the pattern of X-chromosome inactivation was nonrandom in T lymphocytes, but random in granulocytes. While this is the first complete report on the occurrence of thrombocytopenia in a carrier female of WAS as the result of atypical lyonization, it also suggests that expression of the WAS gene occurs at (or extends up to) a later stage than the multipotent stem cell along the hematopoietic differentiation pathway.

Kaposi's sarcoma in a child after autologous bone marrow transplantation for non-Hodgkin's lymphoma.

A case of Kaposi's sarcoma in a child with no serologic evidence of human immunodeficiency virus (HIV) infection is reported. A 7-year-old boy with Stage IV non-Hodgkin's lymphoma, after conventional chemotherapy, underwent autologous bone marrow transplantation (ABMT). Five months later he presented with supraclavicular mass and mediastinal enlargement. A bone marrow biopsy showed hypoplasia with no signs of the underlying disease, whereas the excised mass revealed a typical histologic pattern of Kaposi's sarcoma. The child is currently being treated with recombinant alpha-interferon (alpha-IFN) and regression of the disease has been achieved.

Long term survival after heart transplantation for doxorubicin induced cardiomyopathy.

A 10 year old child developed severe cardiomyopathy after combined, multicycle chemotherapy for Ewing's sarcoma and was treated by heart transplantation with good results. Long term azathioprine and cyclosporin caused only mild impairment of immune function and there were no recurrent infections, local recurrences of the tumour, or distant metastases.

Recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF) in cyclic neutropenia.

We describe the case of a 12-year-old boy affected by cyclic neutropenia, at high risk of developing life-threatening infections, treated with recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF). The drug was effective in reducing the severity of neutropenia and infectious complications in our patient. It was administered for brief periods of time, in contrast to the daily continuous administration reported for rHuG-CSF. Therefore, more extensive studies must be performed to identify the most effective time schedule for the drug. In vitro studies of hemopoietic progenitor cells were useful, in this case, to predict treatment response.

[Bone marrow transplantation in the treatment of severe aplastic anemia]. / Il trapianto di midollo osseo nel trattamento dell'anemia aplastica grave.

Bone marrow transplantation (BMT) in patient affected by severe aplastic anemia (SAA), is successful in 70-80% of cases, when performed with HLA identical brother or syngeneic twin as donors, and in 11-45% of cases when performed from aploidentical-identical related or HLA identical unrelated donor. The different conditioning regimens (Cy alone or in combination with TBI) have shown similar results in the long term outcomes. Cyclosporin-A is very effective in avoiding rejection and controlling GVHD.

[Graft vs host disease in a child undergoing allogeneic bone marrow transplantation]. / La malattia del trapianto contro l'ospite nel bambino sottoposto a trapianto di midollo osseo allogenico.

GVHD has a major role in the morbidity after a BMT, even if the donors are HLA matched siblings. The risks of a severe GVHD increase when using partially matched family donors or matched unrelated donors. An acute GVHD occurs within 100 days from BMT, whereas a chronic GVHD occurs in the first year. Both acute and chronic GVHD are less frequent and severe in children. The experience of the transplant team of Pavia is in agreement with this statement. The incidence of GVHD was extremely low even then compared with the data of the Italian pediatric BMT group. In transplant performed with HLA matched donors the incidences of severe acute and chronic GVHD were 5 and 8%.

Allogeneic bone marrow transplantation in children from other than HLA-identical sibling donor.

Optimal allogeneic bone marrow transplantation (BMT) presupposes the use of a HLA-identical sibling as donor. Unfortunately, only about 30% of patients have an HLA-matched donor, so that the use of alternative donors has been increasingly used. We report an analysis of 13 children transplanted using an HLA-partially matched donor as source of haemopoietic stem cells. They suffered of ALL (3 pts), ANLL (1 pt), SAA (2 pts), Osteopetrosis (1 pt), Wiskott-Aldrich Syndrome (2 pts), Severe Combined Immunodeficiency Disease (2 pts) and Familial Haemophagocitic Lymphohistiocytosis (2 pts). Full engraftment was obtained in all 11 of the patients who survived longer than 14 days and, globally, a moderate incidence of acute GvHD (grade II-IV) was observed in the evaluable patients (3 out of 11 with a percentage of 27%); only a patient of the six survivors more than one hundred days after BMT had severe chronic GvHD (16.6%). Four pts (31%) are actually alive and well (mean follow-up 358 days) with a mean Karnofsky score of 95%. Our data suggest that BMT from HLA-partially matched donors could represent a possible alternative therapeutic strategy in children when a compatible donor is not available. This is especially due to the reduced severity of GvHD in childhood and because of T-cell depleted marrow transplants could obtain more satisfactory results when employed in typical pediatric non-malignant disorders (i.e. immunodeficiencies) rather than in leukemia.