Marco Zaffanello

Relationship between physical inactivity and adiposity in prepubertal boys

OBJECTIVE To study the relationship between the energy expenditure for activity (EEAct), the level of activity and adiposity in a group of 9-year-old boys (n = 28) with different body composition (body weight, 38 +/- 10 kg [range, 23 to 66 kg]; fat mass, 23% +/- 10% [range, 8% to 42%]). METHODS Total energy expenditure (TEE) was measured by means of the heart-rate monitoring method. EEAct was calculated as TEE-(REE+0.1 TEE), where REE is the postabsorptive resting energy expenditure and 0.1 TEE corresponds to the postprandial thermogenesis (approximately 10% of TEE). RESULTS TEE, REE, and EEAct were 9388 +/- 1859, 5154 +/- 642, and 3295 +/- 1356 l J/day, respectively. Daily time devoted to sedentary and nonsedentary activities averaged 290 +/- 155 minutes (range, 69 to 621) and 534 +/- 150 minutes (range, 180 to 783), respectively. Time spent on sedentary activities was directly proportional to fat mass percentage (r = 0.46; p < 0.05). It was the only variable, among the free-living physical-activity [EEAct, TEE/(REE+0.1 TEE) ratio, time spent in nonsedentary and sedentary activities] variables, which remained significantly in the multiple step-down regression analysis final equation (r = 0.46; p < 0.05). CONCLUSIONS The positive relationship between adiposity and time spent on sedentary activities in 9-year-old boys suggests the importance of the role played by muscular activity, at least in the maintenance of obesity in childhood. Prepubertal children should be encouraged to spend less time on sedentary activities to treat and prevent their obesity.

Marked interindividual variability in renal maturation of preterm infants: lessons from autopsy

The kidney of low birthweight preterm infants is characterized by a reduced number of mature nephrons at birth. The aim of the present study was to determine whether, in preterms, active glomerulogenesis occurs in the postnatal period and whether it may compensate the reduced number of nephrons developed during the intrauterine life. Kidney samples were obtained at autopsy from 8 human fetuses, 12 premature infants, and 3 term newborns. Glomerulogenesis, as measured by radial glomerular count (RGC), was markedly decreased in all preterm infants as compared with term newborns. A marked interindividual variability was detected in the level of glomerulogenesis, which, in the vast majority of cases, did neither correlate with the gestational age at birth nor with birthweight. Active glomerulogenesis, as demonstrated by the presence of S-shaped bodies in the subcapsular region, was present in all preterm infants in the perinatal period, but it ceased in a preterm surviving for 3 months. Our data show that active glomerulogenesis continues even after birth for a short period, although it is not able to compensate a marked oligonephronia at birth. As a consequence, the incomplete nephrogenesis typical of all extremely low birthweight preterm infants possibly results in a persistent oligonephronia which should likelihood represent a major risk factors of progressive renal disease in adulthood.

The Kidney from Prenatal to Adult Life: Perinatal Programming and Reduction of Number of Nephrons during Development

Modified embryonic-fetal development resulting in low birth weight may lead to a reduced nephron endowment, hypertension and renal diseases in adulthood. Regarding the involvement of genetic factors, several environmental conditions may also contribute towards reducing the number of nephrons in the fetus and infant, subsequently constituting a health burden in later life. To date no methods of investigation for the early detection of a reduced nephron reserve are available. However, more structured studies should be implemented to investigate the role of angiotensin-converting enzyme inhibitors in managing proteinurias and glomerulosclerosis in children with renal conditions characterized by reduce nephron number and glomerular hypertrophic changes. In view of the current lack of specific methods of investigation and management, close monitoring of children and young adults at risk of reduced renal reserve should be carried out to enhance the early detection of potential changes in renal function.

Maximal aerobic power during running and cycling in obese and non-obese children

Maffeis C, Schena F, Zaffanello M, Zoccante L, Schutz Y, Pinelli L. Maximal aerobic power during running and cycling in obese and non‐obese children. Acta Pædiatr 1994;83:113–16. Stockholm. ISSN 0803–5253

Morphogenesis and molecular mechanisms involved in human kidney development

The development of the human kidney is a complex process that requires interactions between epithelial and mesenchymal cells, eventually leading to the coordinated growth and differentiation of multiple highly specialized stromal, vascular, and epithelial cell types. The application of molecular biology and immunocytochemistry to the study of cell types involved in renal morphogenesis is leading to a better understanding of nephrogenesis, which requires a fine balance of many factors that can be disturbed by various prenatal events in humans. The aim of this paper is to review human kidney organogenesis, with particular emphasis on the sequence of morphological events, on the immunohistochemical peculiarities of nephron progenitor populations and on the molecular pathways regulating the process of mesenchymal to epithelial transition. Kidney development can be subdivided into five steps: (i) the primary ureteric bud (UB); (ii) the cap mesenchyme; (iii) the mesenchymal–epithelial transition; (iv) glomerulogenesis and tubulogenesis; (v) the interstitial cells. Complex correlations between morphological and molecular events from the origin of the UB and its branching to the metanephric mesenchyme, ending with the maturation of nephrons, have been reported in different animals, including mammals. Marked differences, observed among different species in the origin and the duration of nephrogenesis, suggest that morphological and molecular events may be different in different animal species and mammals. Further studies must be carried out in humans to verify at the morphological, immunohistochemical, and molecular levels if the outcome in humans parallels that previously described in other species. J. Cell. Physiol. 227: 1257–1268, 2012.

Immune tolerance with rituximab in congenital haemophilia with inhibitors: a systematic literature review based on individual patients’ analysis

Summary.  Rituximab, a monoclonal antibody against the pan B‐cell antigen CD20, has been successfully used in both adults and children for the management of malignant and non‐malignant immune‐mediated disorders including acquired haemophilia. On the basis of this positive experience, a number of investigators have recently used this agent in patients with congenital haemophilia and inhibitors refractory to first‐line treatments. After a careful electronic and hand search, we have collected 29 studies that included 49 cases. A durable complete remission was obtained in 53% of the cases and no severe adverse events related to rituximab were recorded. A multivariate analysis applied to individual patients’ data identified the diagnosis of a mild/moderate haemophilia and the concomitant treatment with factor VIII concentrates and immunosuppression agents as covariates associated with an increased response to rituximab. Large prospective randomized studies with an adequate follow‐up are needed to confirm these preliminary findings.

Recombinant factor VIIa : An update on its clinical use

Recombinant activated factor VII (rFVIIa, NovoSeven) has been successfully used to treat bleeding episodes in patients with antibodies against coagulation factors VIII and IX. In recent years, rFVIIa has also been employed for the management of uncontrolled bleeding in a number of congenital and acquired haemostatic abnormalities. Based on a literature search, this review examines the current knowledge on therapy with rFVIIa, from the now well-standardized uses to the newer and less well-characterised clinical applications.

Treatment-based literature of Henoch–Schönlein purpura nephritis in childhood

Considerable concern has been expressed on the importance of identifying an improved therapeutic protocol for use in the treatment of childhood Henoch–Schönlein purpura nephritis, primarily due to the unpredictable success shown to date in improving long-term renal outcome. This review focuses on published reports describing the outcomes of therapeutic approaches currently being used in the treatment of pediatric Henoch–Schönlein purpura nephritis, with the aim of providing information that will facilitate a treatment-based approach in children presenting with varying degrees of kidney disease. The conclusions of the authors of this review are that currently prescribed treatments of children affected by Henoch–Schönlein purpura nephritis are not adequately guided by evidence obtained in properly designed, randomized, placebo-controlled trials with outcome markers related to the progression to end stage renal disease (level I evidence). Moreover, firm evidence supporting the best practice to be applied with the aim of delaying the progression of kidney disease is still lacking.

Therapy for Children with Henoch-Schonlein Purpura Nephritis: A Systematic Review

Although severe kidney involvement in children with Henoch-Shonlein purpura (HSP) is rarer than that in adults, morbidity should not be underevaluated and follow-up is mandatory. Some drugs are introduced as well-defined treatment options, others can be promising therapeutic alternatives. Therapy of HSP nephritis in children can range from simply steroids to combined immunosuppressant treatments. The prophylactic treatment for renal complication of patients with HSP has been sometimes suggested, but with conflicting results and ultimately not clearly proven. The treatment of overt HSP nephritis includes steroids and other immunosuppressant drugs. Methylprednisolone pulse therapy and prednisone per os are tested drugs. These steroids could be used in combination with other immunosuppressant drugs, such as cyclosporin A and cyclophosphamide. Unfortunately, of these two drugs, only cyclophosphamide is demonstrated as effective in a recent randomized controlled trial. However, since there are insufficient data and unstructured study designs, ACE-I, azathioprine, mycophenolate mofetil, and urokinase need to be more tested in childhood HSP nephritis. In addition to drugs, other techniques are used to treat the severe form of nephritis. Of these, in a multicenter study, plasmapheresis demonstrated efficacy in delaying the progression of kidney disease. However, no convincing studies have been made to date concerning either intravenous immunoglobulin, factor XIII administration, antioxidant vitamin E, and fish oil to treat HSP nephritis.

Hemophilia and cancer: A new challenge for hemophilia centers

The improved life expectancy of hemophilia patients due to the advances in hemophilia care and factor replacement therapy has permitted to hemophiliacs to reach an older age. As a consequence, age-related diseases, such as cardiovascular disorders and cancer, have been increasingly recognized in such patients. In particular, the management of cancer in people with inherited hemorrhagic disorders represents a new challenge for physicians working in hemophilia centers. The few published literature data document that there is a close relationship between hemophilia and neoplasia. Indeed, the congenital bleeding tendency may influence the cancer in different ways, by interfering with its clinical presentation, diagnosis and treatment. These aspects, along with the epidemiology of cancer in hemophiliacs will be discussed in this review.