Two Masters of Surgery in Parma during the Middle Ages.

During the Middle Ages, Parma, in Northern Italy, undoubtedly represented a landmark for surgical science and practice all around Europe. Around the same period the Salernitan Medical School, already famous since the high Middle Ages, reached its whole scientific role. Due to the importance reached by the School, for centuries several physicians throughout Europe, aiming for an international fame, told they were "Salernitan". One of the most famous examples is represented by Roger Frugardi, or Ruggero Frugardo, or Ruggero da Parma (before 1140 - about 1195), who was widely known as "Rogerius Salernitanus" (Roger of Salerno), meaning that his scientific success was a consequence of the affiliation to the Salernitan Medical School. Roger wrote an important book, the "Practica Chirurgiae" (Surgical Practice), also known as "Rogerina", edited and published by his pupil Guido "the young" of Arezzo. It was the first Handbook of Surgery in the post-Latin Europe, containing important innovations, such as the very first description of a thyroidectomy, thus influencing surgical practice until late Renaissance. The Roger's pupil Rolando dei Capelluti was the successor and extensor of his Master's work. In his work he particularly developed the cranial surgery and the study of neurological diseases (e.g., epilepsy or mania). His masterwork, known as "Rolandina", also influenced European surgery for centuries.

The beginning of smallpox vaccination in the Duchy of Parma.

Maria Luigia (Marie Louise) of Habsburg, daughter of the Austrian Emperor and, as Napoleon Bonaparte's second wife, Empress of the French, after the defeat of the husband in 1814 was relegated to role of Duchesse of Parma, Piacenza and Guastalla. She arrived in Parma in 1816 accompanied by several Austrian army and administrative officials, which were instructing and controlling her, and, willingly, she left to them most of the political and administrative decisions. On the contrary, since the first years she was interested and wanted to take decisions in the field of public health and charity. She opened new specialized hospitals and hospices for poor people, orphans and abandoned children, and, in February of 1820, promulgated the new «Regulations of the vaccinations¼, an exhaustive and specific code, that was taking into consideration the times, the places, and the people who had to vaccinate or to be vaccinated. Moreover, she fixed the modalities, the incentives, the sanctions, and she also nominated a series of people who had to publicize vaccinations and to help the general population inovercoming fears, prejudices and other causes of distrust. The new dispositions increased the number of vaccinated people in the Duchy, saving it from several epidemics that appeared in the following decades in the neighboring regions (Tuscany, Lombardy). In 1831 and 1832 she issued other two ordinances in which she urged the populations and the doctors to increase the vaccinations, probably after a decrease in interest of both, and introduced new practical arrangements to simplify and to facilitate the practice, ensuring and verifying the outcome. The effectiveness of the provisions of Maria Luigia has been shown by the marked decrease in smallpox epidemics throughout her whole reign, until 1847. Meanwhile after the end of the reign, in the second part of the nineteenth century, there was an increase of epidemics, because the following governments of the Bourbons Duchy (1847-1860) and of the united Italy after 1860 were not as diligent and active on spreading vaccinations.

Novelty in hypertension in children and adolescents: focus on hypertension during the first year of life, use and interpretation of ambulatory blood pressure monitoring, role of physical activity in prevention and treatment, simple carbohydrates and uric acid as risk factors.

The present article intends to provide an update of the article "Focus on prevention, diagnosis and treatment of hypertension in children and adolescents" published in 2013 (Spagnolo et al., Ital J Pediatr 39:20, 2013) in this journal. This revision is justified by the fact that during the last years there have been several new scientific contributions to the problem of hypertension in pediatric age and during adolescence. Nevertheless, for what regards some aspects of the previous article, the newly acquired information did not require substantial changes to what was already published, both from a cultural and from a clinical point of view. We felt, however, the necessity to rewrite and/or to extend other parts in the light of the most recent scientific publications. More specifically, we updated and extended the chapters on the diagnosis and management of hypertension in newborns and unweaned babies, on the use and interpretation of ambulatory blood pressure monitoring, and on the usefulness of and indications for physical activity. Furthermore, we added an entirely new section on the role that simple carbohydrates (fructose in particular) and uric acid may play in the pathogenesis of hypertension in pediatric age.

A hand-made supplementary food for malnourished children.

We tested the possibility to prepare a hyperproteic and hyperenergetic supplementary food for malnutrition rehabilitation in children starting from available ingredients in popular markets in Sierra Leone. Twelve residents in Paediatrics from University of Parma, Italy, prepared in a hospital near the capital Freetown with modest technology a mixture of peanut flour, palm oil, milk powder, sugar and vitamins to which they gave the name of "Parma pap". Three hundred and thirty-two malnourished children (mean age 14±6.3 months) who were receiving Feeding Program Supplementations (FPS), were enrolled in the study: 177 participants received randomly FSP portions only (Group 1), and 159 participants were treated with FSP regimen plus a supplement of "Parma pap" (Group 2). Outcomes of the study were computed as WHZ-score increment (Δ value) by subtracting the discharge WHZ-score from the admission WHZ-score. The best Δ-WHZ-scores (>+4) were recorded among participants of Group 2 (64%) rather than in Group 1 (21%; p=0.040). The children receiving FSP portions plus "Parma pap" recovered faster (5.54 week on average) than those treated with FSP regimen only (8.16 on average). The percentage of children who did not recover was higher in Group 1 (25.3%) than in Group 2 (; 13%; p=0.05). A slight positive correlation has been found between WHZ-scores at admission and at the end of the study (r=0.19; p=0.045). During the experience in Sierra Leone we have had the chance to give "Parma pap" to twenty one malnourished children admitted to Xaverian Mission in Makeni, northern Sierra Leone, not taking other supplementary food. Sixteen of these children recovered in 4.9 week on average and five in 6 to 8 weeks. Mean Δ-WHZ-scores ranged between + 1 and + 5. The data from the present study suggest that "Parma pap" could be an effective additional food to FPS regimen in malnutrition recovering. Further researches are needed on the contrary to prove if "Parma pap" could be defined as a veritable ready to use therapeutic food, although this characteristic seems already to result from the experience in Makeni Mission.

Evaluation of tibial osteopathy occurrence in neurofibromatosis type 1 Italian patients.

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disorder characterized by high penetrance, widely variable expressivity and occurrence of specific skeletal changes such as tibial osteopathy (TO). We collected data on patients referred to the Italian Neurofibromatosis Study Group in order to compare clinical features between 49 NF1 patients with TO, and 98 age-matched NF1 patients without TO, and to determine whether the presence of TO is associated with a different risk of developing the typical NF1 complications. We assessed both groups for: age at diagnosis of NF1, gender distribution, family history, gender inheritance, presence of scoliosis, sphenoid wing osteopathy, other skeletal abnormalities, macrocrania, hydrocephalus, plexiform neurofibromas, tumors, optic pathway gliomas, T2H (high-signal intensity areas on T2 weighted brain MRI), epilepsy, headache, mental retardation, cardiovascular malformations, and Noonan phenotype. Patients of both groups were subdivided by gender and re-evaluated for these items. Statistical comparison was carried out between the two groups of patients for each feature. We collected data on type of treatment and on the clinical conditions of NF1-TO patients after follow-up. Patient's age at NF1 diagnosis was significantly younger in NF1-TO subjects compared with NF1 subjects without TO, and the incidence of T2H was significantly reduced in NF1-TO males compared with NF1 males without TO. The presence of TO does not imply that there is an increased risk of developing typical complications of NF1 (e.g., optic pathway glioma, plexiform neurofibroma, etc.), however, it does allow us to make an earlier diagnosis of NF1.

Focus on prevention, diagnosis and treatment of hypertension in children and adolescents.

The European Society of Hypertension has recently published its recommendations on prevention, diagnosis and treatment of high blood pressure in children and adolescents. Taking this contribution as a starting point the Study Group of Hypertension of the Italian Society of Pediatrics together with the Italian Society of Hypertension has conducted a reappraisal of the most recent literature on this subject. The present review does not claim to be an exhaustive description of hypertension in the pediatric population but intends to provide Pediatricians with practical and updated indications in order to guide them in this often unappreciated problem. This document pays particular attention to the primary hypertension which represents a growing problem in children and adolescents. Subjects at elevated risk of hypertension are those overweight, with low birth weight and presenting a family history of hypertension. However, also children who do not present these risk factors may have elevated blood pressure levels. In pediatric age diagnosis of hypertension or high normal blood pressure is made with repeated office blood pressure measurements that show values exceeding the reference values. Blood pressure should be monitored at least once a year with adequate methods and instrumentation and the observed values have to be interpreted according to the most updated nomograms that are adjusted for children's gender, age and height. Currently other available methods such as ambulatory blood pressure monitoring and home blood pressure measurement are not yet adequately validated for use as diagnostic instruments. To diagnose primary hypertension it is necessary to exclude secondary forms. The probability of facing a secondary form of hypertension is inversely proportional to the child's age and directly proportional to blood pressure levels. Medical history, clinical data and blood tests may guide the differential diagnosis of primary versus secondary forms. The prevention of high blood pressure is based on correct lifestyle and nutrition, starting from childhood age. The treatment of primary hypertension in children is almost exclusively dietary/behavioral and includes: a) reduction of overweight whenever present b) reduction of dietary sodium intake c) increase in physical activity. Pharmacological therapy will be needed rarely and only in specific cases.

Vaccination status and prevalence of enteric viruses in internationally adopted children. The case of Parma, Italy.

On age basis, internationally adopted children may have begun or fully completed all required vaccinations, but official documentation from original Countries is frequently insufficient. Aims of this study were to evaluate the seroprotection rate for tuberculosis, hepatitis B, poliomyelitis and tetanus according to immunization cards in 67 children recently adopted and to test the prevalence of enterovirus on faecal specimens. Seroprotection and vaccination status were frequently inconsistent and these results confirm that immunitary surveillance is a cornerstone for the prevention of diseases for which a vaccination is available. (www.actabiomedica.it).

Changes and relationships of IGFS and IGFBPS and cytokines in coeliac disease at diagnosis and on gluten-free diet.

OBJECTIVE: To evaluate changes and relationships of IGFs and IGFBPs, serum interleukin 6 (IL-6) and tumour necrosis factor (TNF)-alpha, and auxological parameters at diagnosis of coeliac disease (CD) and at 6 months and 12 months after starting a gluten-free diet (GFD), compared with a control population. PATIENTS: Twenty patients were enrolled at diagnosis (9 male, 11 female; age 9.6 +/- 0.8 years). A healthy population of 18 subjects (5 male, 13 female; age 11.3 +/- 0.6 years) comparable for age, sex and pubertal status served as controls at baseline. MEASUREMENTS: Blood samples were taken at diagnosis, and at 6 months and 12 months after starting the GFD. Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, IL-6 and TNF-alpha were measured using commercial kits. Height (Ht) standard deviation score (SDS), body mass index (BMI) SDS and Ht velocity SDS were evaluated at diagnosis and at 6 months and 12 months after starting GFD. RESULTS: In CD patients, both Ht SDS and BMI SDS increased during the first year of treatment, and Ht velocity SDS increased during the second 6 months of follow-up (P < 0.05). At diagnosis, IGF-I, IGF-II and IGFBP-3 were lower compared with controls, IGFBP-1 was similar, IGFBP-2, IL-6 and TNF-alpha were higher (P < 0.05). When on GFD, all peptides normalized and IGFBP-1 decreased. The IGF-I/IGFBP-2 and IGF-I/IGFBP-3 molar ratios were significantly reduced at diagnosis compared with those of controls, but were increased for both groups when on GFD. Although there was no apparent abnormality at diagnosis, the IGF-II/IGFBP-2 molar ratio increased significantly on GFD. Ht velocity SDS was positively correlated with IGFBP-3 (P < 0.05) and with the IGF-I/IGFBP-2 molar ratio (P < 0.05). Serum IL-6 was negatively correlated with IGF-I and positively with IGFBP-1 (P < 0.05). CONCLUSIONS: The data obtained from this study confirm changes in the IGF and cytokine systems at diagnosis of CD which tend to normalize on the gluten-free diet. The two systems show relationships with each other and with linear growth.

Rotavirus and not age determines gastroenteritis severity in children: a hospital-based study.

BACKGROUND: The severity of childhood gastroenteritis is generally believed to be age-related rather than aetiology-related. Rotavirus-induced gastroenteritis is more severe than gastroenteritis caused by other enteric pathogens and is also age-related. We thus addressed the question of whether the increased severity of rotavirus-induced gastroenteritis is related to age or to features intrinsic to the agent. STUDY DESIGN: In this multicentre, hospital-based, prospective survey, we evaluated the severity of diarrhoea in rotavirus-positive and rotavirus-negative children up to 4 years of age. Severity was assessed with a score in four groups of age-matched children. RESULTS: Rotavirus was detected in 381 of 911 children. Disease severity was evaluated in 589 cases for which clinical data were complete. The rotavirus-positive and rotavirus-negative groups differed with regards to diarrhoea duration, hospital stay, degree of dehydration and the number of episodes of vomiting. Gastroenteritis was more severe in rotavirus-positive than in rotavirus-negative children. In contrast, none of the main severity parameters differed in the four age groups, irrespective of the presence of rotavirus. CONCLUSIONS: These data provide the evidence that aetiology and not age determines diarrhoeal severity. The demonstration that diarrhoea was more severe in rotavirus-positive children supports the need for a rotavirus vaccine and for studies that address the duration of vaccine protection.

Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis.

OBJECTIVE: In inflammatory bowel diseases, increased serum interleukin (IL)-6 levels are associated with high serum insulin-like growth factor-binding protein 2 (IGFBP-2) levels, and cytokines modify the insulin-like growth factor (IGF)/IGFBP system in models in vitro. In cystic fibrosis (CF) the IGF/IGFBP system has not been extensively studied, and relationships with proinflammatory cytokines have not been explored. The aim of this study was to investigate the IGF/IGFBP system and verify changes dependent on IL-1beta, IL-6, tumour necrosis factor alpha (TNFalpha), and insulin. METHODS: Eighteen subjects with CF (mean age 26.6 +/- 1.1 years) and 18 controls, comparable for age, sex, and body mass index, were enrolled. Serum IGF-I, IGF-II, IGFBP-2, IGFBP-3, IL-1beta, IL-6, TNFalpha, insulin and C-peptide were measured. Different molecular forms of IGFBP-2 and IGFBP-3 were investigated by Western immunoblotting. The patients were analysed as a whole and as two subgroups depending on established clinical criteria (Swachman-Kulczycki score). RESULTS: Patients had higher serum concentrations of IL-1beta, IL-6, TNFalpha and IGFBP-2 than controls. Serum concentrations of IGF-I and IGF-II were significantly lower and insulin and C-peptide levels significantly increased in CF compared with healthy controls whereas IGFBP-3 serum concentrations were similar, with comparable IGF-I/IGFBP-3 and decreased IGF-I/IGFBP-2 and IGF-II/IGFBP-2 molar ratios. From correlation analysis we detected a significant positive correlation between IGFBP-2 and IL-6 and a negative correlation between IGFBP-2 and IGFBP-3. CONCLUSIONS: Our findings suggest that inflammation is an important modulator of the IGF/IGFBP system with an overall reduction in IGF bioactivity in CF.

Albright's hereditary osteodystrophy (pseudohypoparathyroidism type Ia): clinical case with a novel mutation of GNAS1.

Albright's hereditary osteodystrophy is characterized by ectopic calcification and ossification, round face, short hands and feet with short terminal phalanges, short metacarpals (especially 4th and 5th) and absence of the 4th knuckle (brachydactyly type E). Here we describe a case that recently came to our attention of a girl suffering from seizures caused by hypocalcaemia, in which the clinical diagnosis of Albright's hereditary osteodystrophy and Pseudohypoparathyroidism (PHP) (Pseudohypoparathyroidism Ia) was confirmed by DNA molecular analysis. This analysis revealed a novel mutation of GNAS 1, resulting in the nonsense mutation of exon 13 (CAG-->TAG, codon 384). This result expands the spectrum of GNAS1 mutations associated with this disorder.

Brain apparent diffusion coefficient evaluation in pediatric patients with neurofibromatosis type 1.

OBJECTIVE: The most frequent intracranial appearance in children with neurofibromatosis type 1 (NF1) is represented by the presence of hyperintense lesions on T2-weighted images, the so-called "unidentified bright objects" (UBOs). Di Paolo demonstrated that these lesions represent foci of myelin vacuolization with increased water content. The aim of this study was to investigate the isotropic apparent diffusion coefficient (ADC) values within the UBOs and normal-appearing brain and at the regressed UBO sites. METHODS: Fifteen consecutive children with NF1 underwent magnetic resonance diffusion evaluation of the brain. Fifteen healthy age- and sex-matched children constituted the control group. Apparent diffusion coefficient maps were obtained, and regions of interest were placed bilaterally in 8 different areas. Two cortical areas were evaluated using single-pixel analysis. Apparent diffusion coefficient values within the UBOs were calculated by using irregular regions of interest. Regressed UBO sites were investigated by using circular regions of interest. Apparent diffusion coefficient values within the different areas were compared using a t test. RESULTS: Compared with the controls, NF1 patients showed higher ADC values (P < 0.001) in all locations. In the NF1 group, the mean ADC value in the UBOs was higher than in other locations (P < 0.001). The mean ADC value within the regressed UBO sites was higher than in the normal-appearing locations (P < 0.001). CONCLUSIONS: The higher ADC values in children with NF1 suggest an increase in water content of the normal-appearing brain. The UBOs are the areas with the highest water content. The regressed UBOs sites show higher water content than the normal-appearing areas.

Epidemiological aspects of human rotavirus infection in children hospitalized with acute gastroenteritis in an area of northern Italy.

Human rotavirus (HRV) is recognized as the most common cause of severe gastroenteritis in children under 5 years of age. Due to the lack of recent reports about the surveillance of HRV infection in Italy, in this study we assessed the prevalence rate of HRV infection on 1,340 stool samples belonging to 1,264 pediatric patients hospitalized with acute gastroenteritis in the period January 2000--December 2002. The stool samples were submitted to virological investigations by electron microscopy (EM) and conventional cell culture, as well as from January 2002 by RT-PCR for norovirus detection. Reovirus-like particles observed by EM were identified by electropherotyping. Single HRV infections were detected in 302 cases (23.9%, ranging from 19.1% in 2000 to 30.2% in 2001). Mixed infections were observed in 28 cases in which HRV was found to be associated with adenovirus in 16 cases (1.3%), with picornavirus in 4 (0.3%), and with norovirus in 8 (2.1% of the 388 cases examined in 2002). The 3 major epidemic periods of HRV infections were March--May 2000 (66 cases), December 2000--May 2001 (128 cases) and September 2001--April 2002 (105 cases) with peaks in March, January and March, and January, respectively. In the periods of major incidence, single HRV infection accounted even for 52.5% of the gastroenteritis cases monthly examined. According to age distribution, 68.9% (208 cases) of HRV infected children was under 4 years (69.6%: 230/330 cases, including mixed infections) and 16.9% (51 cases) was in the 5-12-year age-group. The epidemiological aspects of HRV infection, also compared to other enteric virus infections, will contribute to assess the magnitude of the problem of HRV in different settings and to devise strategies for intervention.

Leuteinizing hormone responses to leuprolide acetate discriminate between hypogonadotropic hypogonadism and constitutional delay of puberty.

OBJECTIVE: To assess if leuprolide acetate stimulation discriminates between hypogonadotropic hypogonadism (HH) and constitutional delay of puberty (CDP) in males. DESIGN: Case-control study. SETTING: Patients attending an academic research environment. PATIENTS: Only male patients were studied: 10 with HH (group 1, age 16.5 +/- 6.0 years), 8 prepubertal with CDP (group 2, age 14.3 +/- 1.2 years), 6 healthy prepubertal (group 3, age 9.5 +/- 3.3 years), and 8 healthy late-pubertal (group 4, age 15.1 +/- 3.1 years). INTERVENTION(S): Blood samples were obtained after an overnight fast. Leuprolide acetate was then administered SC, and blood samples were drawn at 0, 30, 60, 120, 180 minutes, and 6 and 24 hours after stimulation. MAIN OUTCOME MEASURE(S): Clinical follow-up evaluations of data and serum levels of LH, FSH, 17-hydroxyprogesterone, and testosterone. RESULT(S): Basal LH levels were similar in groups 1 through 3 and differed significantly from those in group 4. Peak serum LH levels were significantly higher in CDP compared with HH (8.9 +/- 1.4 vs. 1.4 +/- 0.2 IU/L). Baseline FSH levels were significantly higher only in pubertal boys (versus the HH group); peak levels did not differ among the groups. Basal and peak testosterone levels were significantly higher only in the control pubertal group when compared to the other groups; peak 17-hydroxyprogesterone concentrations were significantly higher in pubertal controls compared with HH and CDP. CONCLUSION(S): Peak LH responses clearly discriminate HH from CDP. Timing for blood sampling should be fixed at 0, 60, 120, 180 minutes after stimulation.