White blood cells, TNF-α, and interleukin-6 in subjects with infantile colic treated with Lacticaseibacillus rhamnosus GG (ATCC 53103): a randomised prospective study.

Recent metanalysis reported that certain probiotic strains, such as Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus (LGG), seem effective for treatment of infantile colic of exclusively breastfed infants; some reports have also linked probiotics to have an immunological effect, however further investigation are needed to fully understand the exact mechanism. The objective of this study was to assay white blood cells, tumour necrosis factor (TNF)-α and interleukin (IL)-6 values in peripheral blood in subjects treated in a randomised, double-blind, placebo-controlled trial for infantile colic with LGG. Fifty-eight infants were enrolled and followed for a study period of 28 days. Parent were asked to record daily crying time using a structured cry diary. Peripheral white blood cells was assessed and RNA (mRNA) expression of TNF-α and IL-6 was measured using TaqMan real-time PCR-maternal amplification. Infants with colic treated with LGG showed a reduction in daily crying duration after 28 days of treatment and a reduction in values of IL-6 ( P < 0.005) and TNF-α ( P < 0.05); we observe also a significantly decreasing of IL-6 in the placebo group while decrease of TNF-α was not significant in this group. A significant decreased values of monocytes ( P < 0.05) was observed in infants treated with LGG. Our data therefore showed, in addition to crying time reduction, a significant decrease of TNF-α and a significant reduction of monocytes cells in colicky infants treated with LGG, compared to placebo group. This observation supports the hypothesis that probiotics may have anti-inflammatory properties. Further studies are needed to better understand the influence of probiotic on immunity cells.

Congenital esophageal stenosis diagnosed in an infant at 9 month of age.

Esophageal stenosis is a relatively uncommon condition in pediatrics and requires an accurate diagnostic approach. Here we report the case of a 9-month old female infant who presented intermittent vomiting, dysphagia and refusal of solid foods starting after weaning. She was treated for gastroesophageal reflux. At first, radiological investigation suggested achalasia, while esophagoscopy revelaed a severe congenital esophageal stenosis at the distal third of the esophagus. She underwent four endoscopic balloon dilatations that then allowed her to swallow solid food with intermittent mild dysphagia. After 17 months of esomeprazole treatment off therapy impedance-pH monitoring was normal. At 29 months of follow-up the child is asymptomatic and eats without problems.Infants with dysphagia and refusal of solid foods may have undiagnosed medical conditions that need treatment. Many disorders can cause esophageal luminal stricture; in the pediatric age the most common are peptic or congenital. Careful assessment with endoscopy is needed to diagnose these conditions early and referral to a pediatric gastroenterologic unit may be necessary.

Advances on human milk hormones and protection against obesity.

Extensive research shows that breast milk could have positive health effects not limited to infancy, but extend into childhood and adulthood. Recently many studies have provided new evidence on the long—term positive effects of breastfeeding, in particular protection against obesity and type 2 diabetes, suggesting that breast milk may have a role in the programming of later metabolic diseases. The mechanism throughout breastfeeding that exerts these effects has been a major focus of interest for researchers and it is still not completely known. There are some hints for biological plausibility of beneficial effects of breastfeeding including macronutrient intake, hormonal and behavioural mechanisms related to breast milk composition. Breast milk biochemical components, such as protein quantity and quality, polyunsaturated fatty acids, oligosaccharides, cytokines and hormones, in particular leptin, adiponectin and resistin together with the breastfeeding practice itself can influence infants feeding behaviour and regulation of growth and appetite control later in life. Further research is needed to confirm the possibility that hormones present in breast milk exert a metabolic and beneficial effects.

Performance of liver stiffness measurements by transient elastography in chronic hepatitis.

AIM: To compare results of liver stiffness measurements by transient elastography (TE) obtained in our patients population with that used in a recently published meta-analysis. METHODS: This was a single center cross-sectional study. Consecutive patients with chronic viral hepatitis scheduled for liver biopsy at the outpatient ward of our Infectious Diseases Department were enrolled. TE was carried out by using FibroScan™ (Echosens, Paris, France). Liver biopsy was performed on the same day as TE, as day case procedure. Fibrosis was staged according to the Metavir scoring system. The diagnostic performance of TE was assessed by using receiver operating characteristic (ROC) curves and the area under the ROC curve analysis. RESULTS: Two hundred and fifty-two patients met the inclusion criteria. Six (2%) patients were excluded due to unreliable TE measurements. Thus, 246 (171 men and 75 women) patients were analyzed. One hundred and ninety-five (79.3%) patients had chronic hepatitis C, 41 (16.7%) had chronic hepatitis B, and 10 (4.0%) were coinfected with human immunodeficiency virus. ROC curve analysis identified optimal cut-off value of TE as high as 6.9 kPa for F ≥ 2; 7.9 kPa for F ≥ 3; 9.6 kPa for F = 4 in all patients (n = 246), and as high as 6.9 kPa for F ≥ 2; 7.3 kPa for F ≥ 3; 9.3 kPa for F = 4 in patients with hepatitis C (n = 195). Cut-off values of TE obtained by maximizing only the specificity were as high as 6.9 kPa for F ≥ 2; 9.6 kPa for F ≥ 3; 12.2 kPa for F = 4 in all patients (n = 246), and as high as 7.0 kPa for F ≥ 2; 9.3 kPa for F ≥ 3; 12.3 kPa for F = 4 in patients with hepatitis C (n = 195). CONCLUSION: The cut-off values of TE obtained in this single center study are comparable to that obtained in a recently published meta-analysis that included up to 40 studies.

Performance of real-time strain elastography, transient elastography, and aspartate-to-platelet ratio index in the assessment of fibrosis in chronic hepatitis C.

OBJECTIVE: The purpose of this article is to evaluate the diagnostic performance of transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index in assessing fibrosis in patients with chronic hepatitis C by using histologic Metavir scores as reference standard. SUBJECTS AND METHODS: Consecutive patients with chronic hepatitis C scheduled for liver biopsy were enrolled. Liver biopsy was performed on the same day as transient elastography and real-time strain elastography. Transient elastography and real-time strain elastography were performed in the same patient encounter by a single investigator using a medical device based on elastometry and an ultrasound machine, respectively. Diagnostic performance was assessed by using receiver operating characteristic curves and area under the receiver operating characteristic curve (AUC) analysis. RESULTS: One hundred thirty patients (91 men and 39 women) were analyzed. The cutoff values for transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index were 6.9 kPa, 1.82, and 0.37, respectively, for fibrosis score of 2 or higher; 7.3 kPa, 1.86, and 0.70, respectively, for fibrosis score of 3 or higher; and 9.3 kPa, 2.33, and 0.70, respectively, for fibrosis score of 4. AUC values of transient elastography, real-time strain elastography, aspartate-to-platelet ratio index were 0.88, 0.74, and 0.86, respectively, for fibrosis score of 2 or higher; 0.95, 0.80, and 0.89, respectively, for fibrosis score of 3 or higher; and 0.97, 0.80, and 0.84, respectively, for fibrosis score of 4. A combination of the three methods, when two of three were in agreement, showed AUC curves of 0.93, 0.95, and 0.95 for fibrosis scores of 2 or higher, 3 or higher, and 4, respectively. CONCLUSION: Transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index values were correlated with histologic stages of fibrosis. Transient elastography offered excellent diagnostic performance in assessing severe fibrosis and cirrhosis. Real-time elastography does not yet have the potential to substitute for transient elastography in the assessment of liver fibrosis.

Correlation between FIB4, liver stiffness and metabolic parameters in patients with HIV and hepatitis C virus co-infection.

BACKGROUND/AIMS: Assessment of liver fibrosis is crucial in HIV/HCV coinfected patients, in whom metabolic disturbances are frequent. Aims of this study were to analyse the association of two non-invasive liver fibrosis evaluation methods, liver stiffness measurement and FIB4, and their correlation with metabolic parameters. METHODS: This was a single centre cross-sectional study. All patients underwent biochemical and virological assessment, FIB4 score, HOMA and transient elastography. RESULTS: Seventy-five patients were evaluated. Liver stiffness values positively correlated with FIB4 (R = 0.62; p < 0.0001). By ROC curve analysis the optimal cut-off for liver stiffness to identify high FIB4 was calculated as 10.1 kPa. The area under the ROC curve was 0.78 (95% CI 0.78-0.94, sensitivity 83.3%, specificity 80.7%). Liver stiffness values positively correlated with HOMA score (R = 0.31; p = 0.006). CONCLUSIONS: The combination of two non invasive tools provide a useful system for the assessment of fibrosis evolution in patients with HIV-HCV coinfection.

Ghrelin, motilin, insulin concentration in healthy infants in the first months of life: relation to fasting time and anthropometry.

AIMS: This study aimed to investigate: (i) the relation between fasting time and serum ghrelin, motilin and insulin concentrations and (ii) the correlations between these hormones and anthropometrical parameters of infants in the first 18 months of life. PATIENT AND METHODS: A cross-sectional study on 62 term infants was performed. Blood samples for hormonal assay were obtained at least 1 h after feeding. Weight, length and head circumference were recorded. Plasma ghrelin, motilin and insulin concentrations were determined by radioimmunoassay. RESULTS: Ghrelin and motilin had a significant direct correlation with fasting time (r = 0.447; P < 0.001 and r = 0.36; P = 0.004, respectively). We observed a negative influence of insulin on ghrelin levels (beta = -0.32; P = 0.036). Plasma ghrelin levels correlated significantly with age (r = 0.45, P < 0.001), weight (r = 0.31, P = 0.013), head circumference (r = 0.35, P = 0.006) and length (r = 0.39, P = 0.001). A significant correlation emerged between motilin and age (r = 0.45, P < 0.001), weight (r = 0.43, P = 0.001), head circumference (r = 0.47, P < 0.001) and length (r = 0.48, P < 0.001). CONCLUSIONS: Fasting influence on serum ghrelin concentration confirms the role of this hormone as a physiological meal initiator also in infancy. The correlation between ghrelin, anthropometrical parameters and age supports the hypothesis that this hormone could exert an important influence on growth in the first months of life. Considering motilin, age and weight might play a role in determining its secretion; motilin could be considered one of the numerous factors involved in long-term regulation of energy balance.

Serum ghrelin concentration and weight gain in healthy term infants in the first year of life.

OBJECTIVES: Ghrelin, a recently discovered hormone mainly secreted by the stomach, has several metabolic functions including regulation of food intake, energy homeostasis and body weight. There are few studies on this hormone in healthy infants during the first year of life. The aim of this study was to examine the correlations between ghrelin and weight gain in healthy term infants in the first year of life. METHODS: 104 healthy term infants aged 0 to 12 months were included in a cross-sectional study. Anthropometric measurements were assessed and mean weight gain was calculated. Serum ghrelin concentrations have been determined at least 3 hours after feeding by radioimmunoassay test. RESULTS: Ghrelin concentrations were correlated negatively to weight gain (r=-0.302; P=0.003) and positively to age (r = 0.412; P < 0.001), weight (r = 0.374; P < 0.001) and length (r=0.387; P<0.001). In breastfed infants a statistically significant negative correlation between ghrelin concentration and infant weight gain (r=-0.407; P=0.001) was observed, whereas in formula-fed infants this correlation was not statistically significant (r=-0.067; P=0.719). CONCLUSIONS: The negative correlation observed between ghrelin concentration and infant weight gain suggests that ghrelin might also play a role in the regulation of body weight in healthy infants with a physiologic energy balance. Further studies are needed to clarify how ghrelin might be involved in both short-term and long-term energy balance.

Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy.

We tested the hypothesis that the combination of converting enzyme inhibitor (CEI) with losartan (LOS) produces a more profound antiproteinuric effect than either drug alone in normotensive patients with immunoglobulin A (IgA) nephropathy. Eight normotensive (mean blood pressure, 88.9 +/- 2.1 mm Hg) patients with biopsy-proven IgA nephropathy, nonnephrotic proteinuria (protein, 1 to 3 g/d), and normal or slightly reduced creatinine clearance (range, 69 to 119 mL/min) were studied. Clinical evaluations and laboratory tests were performed (1) before CEI treatment (basal) and after (2) CEI alone (CEI, 12 weeks); (3) the combination of CEI and LOS, the latter at a dosage of 50 mg/d (CEI + LOS, 4 weeks); (4) LOS alone (LOS; 50 mg/d; 12 weeks); (5) the combination of LOS and CEI (LOS + CEI, 4 weeks, at the same dosage as CEI + LOS); and (6) a doubled dose of either CEI alone or LOS alone for 4 weeks. CEI and LOS as monotherapy significantly reduced proteinuria by 38% and 30%, respectively. No further reduction of proteinuria was achieved by doubling the dose of CEI or LOS. Both combinations induced a more remarkable reduction of proteinuria (73%; P < 0.05 v other periods) than either drug administered alone. The antiproteinuric effect of CEI or LOS and the more remarkable effect achieved with both combinations was not dependent on the reduction of blood pressure and/or creatinine clearance. In conclusion, this study provides first-time evidence that the combination of CEI and LOS in normotensive patients with IgA nephropathy produces a more profound decrease in proteinuria than either drug. This additive antiproteinuric effect is not dependent on changes in systemic blood pressure and creatinine clearance. Nevertheless, a larger controlled study is required to confirm this novel observation.

Gross hematuria of uncommon origin: the nutcracker syndrome.

Left renal vein hypertension, also called "nutcracker phenomenon" or "nutcracker syndrome," is a rare vascular abnormality responsible for gross hematuria. The phenomenon is attributable to the idiopathic decrease in the angle between the aorta and the superior mesenteric artery with consequent compression of the left renal vein. The entrapment of the left renal vein is not easily detectable by ordinary diagnostic procedures. We report two cases of gross hematuria (persistent in one patient and recurrent in the other) caused by "nutcracker phenomenon." In both cases, no remarkable findings were obtained from medical history, urinary red blood cells morphology, repeated urinalysis, pyelography, cystoscopy, or ureteroscopy. Left renal vein dilation in one case was found with a computed tomography (CT) scan performed on the venous tree of left kidney. The diagnosis of "nutcracker phenomenon" was confirmed by renal venography with measurement of pressure gradient between left renal vein and inferior vena cava in both cases. In one case, the diagnosis was complicated by the presence of Mycobacterium tuberculosis in urine. The "nutcracker phenomenon" is probably more common than thought. Early diagnosis is important to avoid unnecessary diagnostic procedures and complications such as the thrombosis of the left renal vein. Many procedures are available to correct the compression of the left renal vein entrapped between the aorta and the superior mesenteric artery: Gortex graft vein interposition, nephropexy, stenting, and kidney autotransplantation. After surgery, gross hematuria ceases in almost all patients.

[Home enteral nutrition in pediatric age. Based on the Torino experience]. / La nutrizione enterale domiciliare (NED) in età pediatrica. Esperienza del polo di riferimento di Torino.

Enteral nutrition is increasingly used in the management of sick children. Malnutrition may frequently complicate chronic illness in children and nutritional support may be a primary treatment. Particularly children with malnutrition due to certain chronic disorders may need long term enteral nutrition not only in hospital but also at home. We report our experience on home enteral nutrition of 14 patients, aged from 3 months to 15 years. Eleven had a serious weight deficit (< 3 degrees percentile), but none had severe alteration of the biohumoral nutritional parameters. The indication for EN were: in 7 patients cerebral palsy, in 2 cystic fibrosis, and in the other 5 patients congenital heart disease, multiple food intolerance, oesophageal athresia, Werding-Hoffman disease, Costello's Syndrome. Nutritional support was given by nasogastric tube in 6 patients, through gastrostomy in 3 patients and by mouth in 5 patients. We did not see any severe complication due to home enteral nutrition. The practicalities of this nutritional approach are discussed. Although home enteral nutrition was evaluated in a low number of patients, it may have a role in promoting growth of children with inadequate dietary intake or malnutrition and in improving their quality of life.

Bone metabolism changes after transdermal estradiol dose reduction during estrogen replacement therapy: a 1-year prospective study.

Twenty-four surgically menopausal women were randomly allocated to one of two transdermally-administered estrogen replacement therapies (ERT): Group A was administered Estradiol (E2) TTS 0.05 mg/day for 6 months and 0.025 mg/day for the following six months and group B, E2 TTS 0.10 mg/day for the first 6 months and 0.05 mg/day for the following 6 months. For both groups, the treatment regimen was based upon the twice-weekly application of transdermal patches to the lower abdomen for three weeks a month. Serum E2, alkaline phosphatase (AP), osteocalcin (BGP) and urinary hydroxyproline (OHP) excretion levels were measured before the operation, at the beginning of ERT and after 6 and 12 months of treatment. Bone mineral density (BMD) in the distal regions of the forearms was measured by single photon absorptiometry at the start of the study and after 6 and 12 months. In Group A, both mean cortical and trabecular BMD had increased by, respectively, 1.53% and 2.17% after 6 months of therapy; after the second 6 months a significant decrease was observed in both parameters (2.40% and 3.62%, respectively). In Group B, mean cortical and trabecular BMD increased by 1.50% and 2.10%, respectively (significant increase in trabecular bone) after the first 6 months of treatment; after the following 6 months, these values persisted (+0.15 and -0.03%, respectively). Mean AP, OHP and BGP serum levels rose after the operation. In Group A, AP and OHP showed a significant decrease after the first 6 months (-34.90% and -30.90%), followed by an increase at the last evaluation of 22.50% and 35.50%, that reached statistical significance only for OHP.(ABSTRACT TRUNCATED AT 250 WORDS)

[Lipidemic alterations in a child with acute lymphoblastic leukemia in treatment with L-aspariginase]. / Alterazioni lipidiche in una bambina affetta da leucemia linfoblastica acuta (LLA) in trattamento con L-asparaginasi.

The case of a child treated for Acute Lymphoblastic Leukemia (LLA) with high-dose L-asparaginase, (HD L-ase) presented alteration who of lipidemic values (rise of total cholesterol and triglyceride values) without toxicity is described. This finding has previously been reported in only a few patients. Parameters normalized with dietetic regimen. The authors underline the importance of the control, in patient during HD L-ase treatment of lipidic values too, especially when parents also have similar alterations.

Comparative study of progesterone plasma levels after nasal spray and intramuscular administration of natural progesterone in menopausal women.

11 mg natural progesterone (P) was administered to 20 healthy menopausal women by means of a nasal spray or intramuscular injection. Circulating P levels were calculated at various times after administration. The spray formulation yielded a CMax of 3.75 ng/ml at TMax = 60 min, the area under the curve (AUC)0-720 being 1,481.6 +/- 343. Intramuscular administration yielded a mean CMax of 4.137 ng/ml at TMax = 240 min, the AUC0-720 being 2,491.2 +/- 540. P absorption was faster through the nasal than through the intramuscular route, but intramuscular administration led to high serum levels for a much longer period.

[Hodgkin's disease in childhood]. / La malattia di Hodgkin in età pediatrica.

Only in these latest years has been possible to consider Hodgkin disease (HD) as a neoplastic syndrome, thank of immunohistochemistry and cytogenetic techniques which have confirmed the monoclonal origin of typical cellular marker of disease: the Reed-Sternberg cell (R-S cell). Interesting associations have been observed between children suffering from HD and the positivity of EBV antigen above all in the socio-economically developed countries. The histopathologic classification of HD is divided in four sub-types, with different incidence in the pediatric age: the nodular sclerosis and the mixed cellularity are more rap-presented than the lymphocyte predominance and mostly the lymphocyte depletion. Histopathologic classification is essential for the prognosis and a correct therapeutic approach to disease. The management of HD is based on chemotherapy and radiotherapy associated; the results of treatment are more and more encouraging with a global survival over 95%. Sequelae of treatment are reduced in modern therapeutic trials: in particularly injury to somatic growth, cardiopulmonary system, gonadal and thyroid functionality is reduced by using low dose and involved fields for the early stage patients. The most important sequela in children treated for HD is the risk to developed a second malignant neoplasm; in particularly acute nonlymphocytic leukemia and non Hodgkin's lymphoma. In patients treated with radiotherapy alone increase the risk to develop solid tumors like sarcomas and carcinomas, which can appears several years after diagnosis.

Progesterone administration by nasal spray in menopausal women: comparison between two different spray formulations.

The aim of the study was to compare the bioavailability of progesterone dissolved in almond oil or dimethicone, and administered by nasal spray. Twenty healthy menopausal women were randomly allocated to treatment by four doses of intranasal spray either of a progesterone solution in almond oil, 2 mg/0.1 ml, corresponding to a total dose of approximately 11 mg of progesterone, or a progesterone solution in dimethicone 5 mg/0.1 ml corresponding to a total dose of approximately 28 mg of progesterone. Circulating progesterone levels were calculated at various time intervals following administration. The formulation with almond oil yielded a maximum progesterone concentration (Cmax of 3.75 ng/ml at Tmax = 60 min, and the area under the curve (AUC0-720) value was 1481.6 +/- 343. The formulation with dimethicone yielded a mean Cmax of 1.049 ng/ml at Tmax = 30 min; the AUC0-720 value was 302.06 +/- 37.5. Therefore, bioavailability of progesterone dissolved in almond oil proved to be largely superior compared to the solution in dimethicone. The crucial role of the carrier in the spray formulations is discussed; in addition to ensuring clinical safety, it must have good solubility for progesterone, be fluid enough to enable efficient 'spraying' and also must allow progesterone to be absorbed through the nasal mucosa.