Demethylation analysis of the FOXP3 locus shows quantitative defects of regulatory T cells in IPEX-like syndrome.

Immune dysregulation, Polyendocrinopathy, Enteropathy X-linked (IPEX) syndrome is a unique example of primary immunodeficiency characterized by autoimmune manifestations due to defective regulatory T (Treg) cells, in the presence of FOXP3 mutations. However, autoimmune symptoms phenotypically resembling IPEX often occur in the absence of detectable FOXP3 mutations. The cause of this "IPEX-like" syndrome presently remains unclear. To investigate whether a defect in Treg cells sustains the immunological dysregulation in IPEX-like patients, we measured the amount of peripheral Treg cells within the CD3(+) T cells by analysing demethylation of the Treg cell-Specific-Demethylated-Region (TSDR) in the FOXP3 locus and demethylation of the T cell-Specific-Demethylated-Region (TLSDR) in the CD3 locus, highly specific markers for stable Treg cells and overall T cells, respectively. TSDR demethylation analysis, alone or normalized for the total T cells, showed that the amount of peripheral Treg cells in a cohort of IPEX-like patients was significantly reduced, as compared to both healthy subjects and unrelated disease controls. This reduction could not be displayed by flow cytometric analysis, showing highly variable percentages of FOXP3(+) and CD25(+)FOXP3(+) T cells. These data provide evidence that a quantitative defect of Treg cells could be considered a common biological hallmark of IPEX-like syndrome. Since Treg cell suppressive function was not impaired, we propose that this reduction per se could sustain autoimmunity.

Role of respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences.

In order to evaluate the infectious agents associated with the first episode of severe acute wheezing in otherwise healthy infants and to define the role of each of them in recurrences, 85 patients in Italy, aged <12 months, hospitalized because of a first acute episode of wheezing, were prospectively enrolled between 1 October 2005 and 31 March 2006. Upon enrollment, nasopharyngeal swabs were collected for the real-time PCR detection of respiratory syncytial virus (RSV) types A and B, influenza virus types A and B, adenovirus, parainfluenza viruses types 1, 2, 3 and 4, rhinovirus, human metapneumovirus, human coronavirus types 229E, OC43, NL63, and HKU1, bocavirus, enterovirus, and paraechovirus; nasopharyngeal aspirates were also obtained to detect atypical bacteria. At least one infectious agent was identified in 76 children (89.4%). RSV was the most frequently detected pathogen and its prevalence was significantly higher than that of the other pathogens in both age groups, and significantly higher in the children aged 3-12 months than in those aged <3 months. Only the children with RSV infection experienced recurrent wheezing. Viral load was significantly higher in children with than in those without recurrent wheezing. This study shows that RSV is the main reason for hospitalization during the first wheezing episode in infants, and that it appears to be the only pathogen associated with a high frequency of recurrences. A high viral load seems to be strictly related to the likelihood of recurrence.

Hepatitis C virus (HCV) genotypes in 373 Italian children with HCV infection: changing distribution and correlation with clinical features and outcome.

BACKGROUND AND AIMS: Little is known of hepatitis C virus (HCV) genotypes in HCV infected children. This retrospective, multicentre study investigated genotype distribution and correlation with clinical features and outcome in a large series of Italian children. METHODS: Between 1990 and 2002, 373 HCV RNA positive children, consecutively recruited in 15 centres, were assayed for genotypes by a commercial line probe assay. RESULTS: The following genotype distribution pattern was recorded: genotype 1b = 41%; 1a = 20%; 2 = 17%; 3 = 14.5%; 4 = 5%; other = 2.5%. The prevalence of genotypes 1b and 2 decreased significantly (p<0.001) among children born from 1990 onwards compared with older children (46% v 70%) while the rate of genotypes 3 and 4 increased significantly (from 8% to 30%). Children infected with genotype 3 had the highest alanine aminotransferase levels and the highest rate of spontaneous viraemia clearance within the first three years of life (32% v 3% in children with genotype 1; p<0.001). Of 96 children enrolled in interferon trials during the survey, 22% definitely lost HCV RNA, including 57% of those with genotypes 2 and 3. CONCLUSION: HCV genotypes 1 and 2 are still prevalent among infected adolescents and young adults in Italy but rates of infection with genotypes 3 and 4 are rapidly increasing among children. These changes could modify the clinical pattern of hepatitis C in forthcoming years as children infected with genotype 3 have the best chance of spontaneous viraemia clearance early in life, and respond to interferon in a high proportion of cases.

Costs associated with outpatient diarrhoea in infants and toddlers: a nationwide study of the Italian Society of Paediatric Gastroenterology and Hepatology (SIGEP).

BACKGROUND: As diarrhoea mortality is negligible in Italy, other costs should be considered when planning health strategies. Little is known about the costs associated with diarrhoea in Italian children. AIMS: To assess the costs associated with outpatient infantile diarrhoea in Italy. METHODS: Primary care paediatricians from five regions filled in a questionnaire for the first 10 children (1-47 months) they visited for acute diarrhoea during a 3-month period. RESULTS: We analysed 473 questionnaires. Mean age (standard deviation) of children was 21 (11) months; mean duration of diarrhoea (standard deviation) was 4.3 (2.6) days. An overall cost of 110 (137) euro per episode was estimated, with significant difference between children younger and older than 36 months (116 euro versus 72 euro). Missed work by relatives accounts for 75% of the cost. The parents of children attending a day-care centre had an increased risk to miss work (relative risk = 2.15). A weak relationship was found between days of diarrhoea and missed work (r = 0.30); it could be estimated that the diarrhoea should be shortened by about 4 days in order to save I day of missed work. CONCLUSIONS: Acute outpatient diarrhoea is associated with a significant financial burden in Italy. Simply shortening the diarrhoea does not seem to be the most expeditious way to reduce the cost of diarrhoea itself.

[Small bowel overgrowth: a frequent complication after abdominal surgery in newborns]. / Sindrome dell'intestino infetto: complicanza frequente dopo chirurgia addominale nel neonato.

BACKGROUND/PURPOSE: Surgery for congenital or acquired gastroenterological disorders, and particularly that associated with short bowel, is not infrequently complicated by Small Bowel Bacterial Over growth (SBBO). Aim of this study is to evaluate the clinical course of children undergoing bowel surgery in the newborn period, assessing the development of SBBO and the response to intensive treatment with a "bowel cocktail" of gentamycin, metronidazole and cholestyramine. METHODS: 17 children with various conditions were studied clinically and by Breath Hydrogen Test (fasting and after glucose). 14 children underwent more than one procedure. All children were treated with overall "bowel cocktail" of gentamycin, metronidazole and cholestyramine. RESULTS: 5 children recovered after one course of treatment and 11 children relapsed at least once and required further courses of therapy. One child died from TPN related liver failure and another following a liver and small bowel transplant for short bowel syndrome. A third child required total intestinal tube splinting according to Sauer and another one required a tapering of the preatretic enlarged jejunal loop. CONCLUSIONS: Our study suggests that children undergoing bowel surgery in the neonatal period and those having more than one procedure are at greater risk of developing small bowel bacterial overgrowth postoperatively. Interestingly, loss of the ileocecal valve was not associated with an increased risk of bacterial overgrowth.

Transthoracic and transesophageal echocardiographic indices predictive of sinus rhythm maintenance after cardioversion of atrial fibrillation: an echocardiographic study during direct current shock.

BACKGROUND: Up to 57% of atrial fibrillation (AF) recurrences after cardioversion take place during the first 30 days following direct current shock (DCS) delivery. Previous echocardiographic studies on sinus rhythm (SR) maintenance after cardioversion have focused mainly on parameters recorded before DCS, while other studies have reported on the indices recorded soon after delivery of the shock. METHODS: Therefore, we investigated 18 patients with nonrheumatic AF, selected to undergo DCS, by both transthoracic (TTE) and transesophageal (TEE) echocardiography performed within 10 minutes before and after the electrical shock delivery. TTE was utilized for the evaluation of left atrium and left ventricle shape as well as for mitral Doppler flow sampling, while TEE was used to evaluate left atrial appendage (LAA) morphology and function, to score the LAA spontaneous echo contrast, and to evaluate the flow of left superior pulmonary vein; the transesophageal probe was left in situ during the electrical procedure. Thirty days after cardioversion, 10 (55%) patients maintained SR (Group 1) while 8 (45%) reverted to AF (Group 2). We compared the mean values of the parameters recorded in the two groups both before and after DCS. RESULTS: Although many parameters of pre- and postcardioversion analysis proved to be significantly different between the two groups, the most marked differences were exhibited by the following postcardioversion indices: Peak Doppler flow velocity of the end-diastolic mitral flow (30.10 +/- 5.24 vs. 20.50 +/- 6.32 cm/sec, P = 0.003); sum of peak velocities of the end-diastolic contraction (A) and relaxation (A(1)) of LAA (A + A(1) = 58.20 +/- 17.02 vs. 31.25 +/- 9.27 cm/sec, P = 0.001); duration of A + A(1) (162.70 +/- 27.01 vs. 133.75 +/- 5.31 msec, P = 0.002); and sum of durations of the early diastolic forward (E) and reverse (E(1)) flow of LAA (101.90 +/- 35.15 vs. 53.33 +/- 16.33 msec, P = 0.006). CONCLUSIONS: Using a single echocardiographic examination during DCS and after induction of anesthesia, without further discomfort to patients, we were able to identify useful parameters for the prediction of future electrical activity of the heart before as well as soon after DCS. Postcardioversion indices, derived by both TTE and TEE, were even more predictive of SR maintenance after 1 month than precardioversion parameters.

Bone mineral loss through increased bone turnover in HIV-infected children treated with highly active antiretroviral therapy.

OBJECTIVES: To evaluate the occurrence and define the aetiology of osteopenia in children receiving highly active antiretroviral therapy (HAART). METHODS: Bone mineral density (BMD) of total body and lumbar spine (L2-L4) was assessed by dual-energy X-ray absorptiometry in 40 children vertically infected with HIV: 35 taking HAART and five naive to any antiretroviral treatment (untreated). Six HAART-treated children showed clinical evidence of lipodystrophy. N-terminal propeptide of type-I procollagen (PINP), bone-specific alkaline phosphatase (BALP) and N-terminal telopeptide of type I collagen (NTx) were measured. Results were compared with those obtained in 314 healthy controls. Differences between HIV-positive and healthy children and within the HIV-positive group were assessed by multivariate analyses, controlling for confounding variables (age, sex, weight and height). RESULTS: HAART-treated children showed lower spine BMD values than untreated (P = 0.045) and healthy (P = 0.004) children and lower total body BMD values than untreated (P = 0.012) and healthy (P < 0.0001) children. Spine and total body BMD were similar between untreated and healthy children. Total body BMD was lower (P < 0.005) in HAART-treated children with lipodystrophy than in untreated patients, while children on HAART but without lipodystrophy had intermediate values. BALP, PINP and NTx were similar among untreated and healthy children. HAART-treated children had higher BALP levels than healthy (P = 0.0007) and untreated (P = 0.045) children. PINP values showed the same trend as BALP. HAART-treated children had higher NTx urine levels than healthy (P < 0.0001) and untreated (P = 0.041) children. CONCLUSIONS: HAART seems a new risk factor for life-long osteoporosis in children. An increased rate of bone turnover causes BMD decrease. Severity of osteopenia seems to be related to lipodystrophy.

Long-term effects of spinal cord stimulation on myocardial ischemia and heart rate variability: results of a 48-hour ambulatory electrocardiographic monitoring.

BACKGROUND: Spinal cord stimulation (SCS) has analgesic properties and may be used to treat pain in patients with therapeutically refractory angina who are unsuitable for myocardial revascularization. Some studies have also demonstrated an anti-ischemic effect. The aim of this study was to evaluate the long-term persistence of the effects of SCS on myocardial ischemia and on heart rate variability. METHODS: Fifteen patients (9 males, 6 females, mean age 76 +/- 8 years, range 58-90 years) with severe refractory angina pectoris (Canadian class III-IV), on optimal pharmacological therapy, unsuitable for myocardial revascularization and treated with SCS for a mean follow-up of 39 +/- 27 months (range 9-92 months) were studied. Eleven patients had had a previous myocardial infarction and 5 a coronary artery bypass graft. The mean ejection fraction was 54 +/- 7% (range 36-65%). All patients underwent 48-hour ambulatory ECG monitoring and were randomly assigned to 24 hours without SCS (off period) and 24 hours with SCS (on period). The primary endpoints were: number of ischemic episodes, total duration of ischemic episodes (min), and total ischemic burden (mV*min). RESULTS: The heart rate was not statistically different during the off and on SCS periods (median 64 and 67 b/min respectively). The number of ischemic episodes decreased from a median of 6 (range 0-29) during the off period to 3 (range 0-24) during the on period (p < 0.05). The total duration of ischemic episodes decreased from a median of 29 min (range 0- 186 min) during the off period to 16 min (range 0-123 min) during the on period (p < 0.05). The total ischemic burden decreased from a median of 2.5 mV*min (range 0-19.5 mV*min) during the off period to 0.8 mV*min (range 0-13 mV*min) during the on period (p = NS). The heart rate variability parameters were similar during the on and off periods. CONCLUSIONS: SCS exerts long-term anti-ischemic effects.

Efficacy of oral pancreatic enzyme therapy for the treatment of fat malabsorption in HIV-infected patients.

BACKGROUND: Nutrient malabsorption is a negative prognostic factor in acquired immunodeficiency syndrome and recent studies have shown that pancreatic insufficiency is a codetermining factor of malabsorption. AIMS: To evaluate the effectiveness of open-label oral pancreatic enzyme supplementation therapy in acquired immunodeficiency syndrome patients with fat malabsorption. PATIENTS AND METHODS: Twenty-four consecutive patients with human immunodeficiency virus infection and fat malabsorption were recruited (11 males, 13 females; median age, 9.1 years). Faecal fat loss was evaluated by steatocrit assay at entry to the study (T-0), after 2 weeks (T-1) without pancreatic enzyme treatment and after a further 2 weeks (T-2) of treatment with pancreatic extracts (Creon 10 000 at a dose of 1000 units of lipase per gram of ingested dietary fat). Faecal elastase-1 and chymotrypsin were assayed at entry. RESULTS: Six patients (25%) had abnormally low elastase-1 and/or chymotrypsin faecal concentration. In all patients, steatocrit values were elevated at both T-0 and T-1. Five patients proved intolerant to pancreatic enzyme treatment because of the onset of abdominal pain, and therapy was discontinued. In the 19 patients who concluded the study, steatocrit values during pancreatic enzyme treatment (T-2) were significantly lower than at entry (P < 0.0001). At T-2, in eight of 19 patients, steatocrit values were within the normal limit and the frequency of cases cured or improved on pancreatic enzyme therapy (at T-2) was significantly higher than that observed during the previous study period without enzyme treatment (T-1) (P < 0.01). A positive significant correlation was found between steatocrit values at entry and the Centers for Disease Control class (P < 0.0005); also, the decrease in steatocrit values during pancreatic enzyme therapy (difference between steatocrit value at T-2 and steatocrit value at T-0) positively correlated with the Centers for Disease Control class (P < 0.05). CONCLUSIONS: This pilot, open-label study showed that pancreatic enzyme supplementation therapy is highly effective in reducing faecal fat loss in human immunodeficiency virus-infected patients with nutrient malabsorption. Further double-blind studies must be undertaken to verify these results and, if they are confirmed, pancreatic enzymes can be added to our weapons in the fight against human immunodeficiency virus-associated nutrient malabsorption.

An epidemiological survey of hepatitis C virus infection in Italian children in the decade 1990-1999.

BACKGROUND: A retrospective-prospective survey of Italian children with hepatitis C virus (HCV) infection was planned in 1998 to explore the epidemiologic features of infection during the past decade. METHODS: Anti-HCV-positive patients (or HCV RNA-positive infants) aged 1 month to 16 years, consecutively observed in 20 pediatric Institutions, were considered. An anonymous epidemiologic questionnaire based on clinical records was used. RESULTS: From 1990 through March 1999, 606 patients were observed (296 boys, average age 5.8 years). Maternal infection (46% of cases) and blood transfusions (34%) were the most frequent risk factors. Of 279 infected mothers, 61% did not recall a putative source of infection (by history, many could possibly have had exposure through routes such as therapeutic injections with nondisposable material), whereas 94 (34%) admitted drug abuse, including 49 (17%) coinfected with human immunodeficiency virus (HIV). Only 157 (26%) children were born after 1991: 90% of their mothers were infected (11% were HIV coinfected vs. 25% mothers of older children, P < 0.01). CONCLUSIONS: Maternal infection is a prominent source of pediatric HCV infection in Italy. The fact that most mothers had a history of covert exposure to HCV, probably through percutaneous routes that are no longer operating, and that the number of those with HIV coinfection has decreased suggests that the frequency of pediatric infection could decrease in the future.

[Epidural spinal stimulation in the treatment of refractory angina pectoris. Its clinical efficacy, complications and long-term mortality. An Italian multicenter retrospective study]. / La stimolazione spinale epidurale nel trattamento dell'angina pectoris refrattaria. Efficacia clinica, complicanze e mortalità a lungo termine. Studio retrospettivo multicentrico Italiano.

BACKGROUND: Spinal cord stimulation has been used for many years in the treatment of refractory angina pectoris. Its anti-anginal and anti-ischemic effect has been well documented in several studies, but the long-term efficacy, safety and survival rate are not well known. The aim of this study was to carry out a retrospective analysis of a series of patients from the Italian Multicenter Registry, the data of which were collected in five centers, by means of a questionnaire. METHODS: One hundred and thirty patients (83 males, 47 females, mean age 74.8 +/- 9.8 years) were submitted to spinal cord stimulator implantation for refractory angina pectoris in the period 1988-1995 and controlled during a mean follow-up of 31.4 +/- 25.9 months. A previous myocardial infarction had already occurred in 69.3% of patients, whereas in 67.6% multivessel coronary artery disease was documented. A left ventricular dysfunction (ejection fraction < 0.40) was present in 34% of patients; bypass surgery and coronary angioplasty were performed in 49.6% and in 27% of patients respectively. In 96.3% of cases revascularization procedures were not advisable. RESULTS: A complete follow-up of 116 patients (89.2%) was available. The spinal cord stimulator induced a significant reduction in NYHA functional class from 2.5 +/- 1.2 to 1.5 +/- 0.9 (p < 0.01). During the follow-up 41 patients (35.3%) died, and in 14.2% a new acute myocardial infarction developed. The total percentage of minor spinal cord stimulation-related complications was 6.8%. No major complications occurred. The annual total mortality rate was 6.5%, whereas the cardiac mortality rate was 5%. Compared to the survivors, patients who died showed a higher incidence of left ventricular dysfunction, previous myocardial infarction and bypass surgery at implantation. CONCLUSIONS: In our experience, spinal cord stimulation is an effective therapy in patients affected by refractory angina pectoris and who cannot undergo revascularization procedure. The complication rate is low, with the total and cardiac mortality showing a trend as that reported for patients with similar coronary disease.

Body composition in HIV-infected children: relations with disease progression and survival.

BACKGROUND: Malnutrition is common in HIV-infected children, but the body compartment that is most affected has been ill defined. OBJECTIVES: Our objectives were to 1) compare the fat-free mass (FFM) of children with HIV infection with that of control children, 2) assess the contribution of FFM to body weight in HIV-infected children compared with that of control children, and 3) study the relations between body weight, FFM, and mortality. DESIGN: A cross-sectional study was performed in 86 HIV-infected and 113 uninfected children (mean ages: 6.9 and 7.7 y, respectively). FFM was estimated from single-frequency bioelectrical impedance analysis by using 3 different published equations; a further estimate was obtained from triceps-skinfold-thickness measurements. RESULTS: All 4 estimates of body composition showed that FFM in HIV-infected children was significantly less than in control children of similar age. However, FFM as a percentage of body weight was not significantly different between groups. In the whole group of infected children, an age-specific z score < -2 for weight and for FFM was significantly associated with an increased risk of death [relative risk (95% CI) = 11.4 (3.1, 41.0) and 5.1 (1.5, 18.2), respectively]; when only children with more severe disease were considered, only z score for weight was significantly associated with an increased risk [4.6 (1.4, 14.9)]. CONCLUSIONS: These findings suggest that no preferential catabolism of FFM occurs in HIV-infected children and that body weight for age is a better prognostic indicator than is FFM estimated by bioelectrical impedance analysis.

Outcome of mother to infant acquired GBV-C/HGV infection.

Twelve children born to hepatitis C virus antibody GBV-C/HGV RNA positive mothers who acquired GBV-C/HGV infection by the vertical or perinatal route were studied. Most (91%) were persistently GBV-C/HGV RNA positive up to 12 months of age. Four out of six cases who acquired GBV-C/HGV alone had normal alanine amino transferase activities. Long lasting evidence of hepatocellular injury was detected only in children with GBV-C/HGV and hepatitis C virus and HIV coinfection.

[Effects of spinal cord stimulation on regional myocardial blood flow in patients with refractory angina. A positron emission tomography study]. / Effetti della stimolazione spinale epidurale sul flusso miocardico regionale in pazienti con angina pectoris refrattaria. Uno studio con tomografia ad emissione di positroni.

BACKGROUND: Spinal cord stimulation (SCS) is an alternative therapy in patients with refractory angina pectoris when coronary revascularization cannot be performed. Several hypotheses have been given to explain the effects of SCS in reducing the number and the intensity of anginal crises. These hypotheses include possible variations in myocardial blood flow (MBF). The aim of our study was to assess regional MBF in a group of patients with spinal cord stimulator, using positron emission tomography (PET). METHODS: We studied 15 patients (9 male and 6 female), mean age 74 +/- 7 years, who were carriers of a spinal cord stimulator implanted 17 +/- 14 (range 1-48) months before. All patients had been affected with angina pectoris that was refractory to maximal tolerated pharmacological therapy. Eight patients had had a previous myocardial infarction and four patients had undergone a revascularization procedure. Every patient underwent two PETs with nitrogen-13-ammonia as the perfusion tracer. The first one was performed with the stimulator switched off for at least 20 hours, and the second one with the stimulator switched on for at least 4 hours. The quantitative evaluation of regional MBF (anterior, inferior, lateral, septal walls and apex) was performed with Patlak graphic analysis. The normal value of basal MBF in our laboratory is 0.6-1 ml/min/g. RESULTS: The mean value of MBF increased from 0.72 +/- 0.33 ml/min/g with the stimulator off, to 0.80 +/- 0.33 ml/min/g with it on (p = 0.004). An increase in regional myocardial perfusion, with the stimulator on as opposed to off, was observed in 47 (62%) of the 75 regions studied. With the stimulator on, in comparison with off, the value of MBF increased from 0.45 +/- 0.11 ml/min/g to 0.56 +/- 0.19 (p = 0.0001) in the 35 regions with low basal MBF (< 0.6 ml/min/g), and from 0.77 +/- 0.14 ml/min/g to 0.92 +/- 0.29 ml/min/g (p = 0.013) in the 23 regions with basal MBF between 0.6 and 1 ml/min/g. Instead, in the 17 regions with high basal MBF (> 1 ml/min/g) it decreased with the stimulator on instead of off, going from 1.22 +/- 0.20 to 1.13 +/- 0.22 ml/min/g (p = 0.112). CONCLUSIONS: Our study suggests that the beneficial effects of SCS in refractory angina may also be related to an increase in mean MBF and to a redistribution of MBF between the regions with low or normal basal flow and the regions with high basal flow.

Pancreatic dysfunction and its association with fat malabsorption in HIV infected children.

BACKGROUND: Nutrient malabsorption frequently occurs in HIV infected children, but very few studies have investigated exocrine pancreatic digestive capacity in these cases. AIMS: To investigate pancreatic function in HIV infected children and to determine whether faecal fat loss, a prominent feature of intestinal dysfunction, is associated with pancreatic dysfunction. PATIENTS: Forty seven children with HIV infection without apparent pancreatic disease and 45 sex and age matched healthy controls. METHODS: Pancreatic function was evaluated by measuring elastase 1 concentration and chymotrypsin activity in stools by ELISA and colorimetric methods, respectively. Intestinal function was evaluated by measuring fat and protein loss by the steatocrit method and by faecal alpha1 antitrypsin concentration. RESULTS: 14 (30%) had abnormal pancreatic function tests: seven had isolated elastase activity deficiency, three isolated chymotrypsin deficiency, and four pancreatic deficiencies in both enzymes. Patient enzyme values were significantly lower than those of controls. Low faecal pancreatic enzymes were not associated with symptoms. Twelve children had steatorrhoea and four had increased alpha1 antitrypsin. Steatorrhoea was significantly associated with reduced faecal pancreatic enzymes. There was a significant negative correlation between elastase 1 concentration and steatocrit. Children with pathological faecal elastase 1 or chymotrypsin values did not differ from the other HIV infected children with respect to nutritional and immunological status, stage of HIV disease, presence of opportunistic infections, or drug administration. CONCLUSIONS: Abnormal pancreatic function tests are a frequent feature of paediatric HIV infection; this condition is associated with steatorrhoea, which probably contributes to the disease.

Serum pancreatic enzymes in human immunodeficiency virus-infected children. A collaborative study of the Italian Society of Pediatric Gastroenterology and Hepatology.

BACKGROUND: Numerous studies have shown pancreatic disease in adult human immunodeficiency virus (HIV)-infected patients, but there are very few reports on pediatric patients. Our aim was to determine the prevalence of increased serum pancreatic enzyme levels and their relationship to clinical manifestations of acute pancreatitis in HIV-infected children. METHODS: Forty-seven consecutive, symptomatic HIV-infected children (24 male; median age, 7.3 years; range, 1-17 years) and 45 sex- and age-matched controls without gastroenterologic disease were enrolled. In all subjects serum total amylase, pancreatic amylase, and lipase were assayed with commercial kits. The following were recorded: disease progression (CDC class), nutritional status (weight Z-score), CD4 lymphocyte count, drug treatment during the previous 12 months, presence of opportunistic infections, clinical evidence of acute pancreatitis (increased serum pancreatic enzymes associated with vomiting, abdominal distention, and intolerance when eating). RESULTS: Ten of 47 HIV patients had increased serum total amylase values; however fewer patients had increased specific pancreatic enzymes: 6 of 47 for pancreatic amylase (range, 1.8- to 19.8-fold normal limit) and 7 of 47 for lipase (range, 1.4- to 4-fold normal limit). Values were normal in all controls. Two HIV patients with increased total amylase had clinically evident parotid inflammation. None of the patients with increased serum pancreatic amylase and/or lipase had clinical symptoms of acute pancreatitis. Regression analysis showed no correlation between increased serum pancreatic enzyme levels and disease progression (CDC class), immunologic status (CD4 count), nutritional status, drug administration, or opportunistic infections. CONCLUSIONS: Fifteen per cent of HIV-infected children had biochemical evidence of pancreatic involvement; however, this condition was unrelated to clinical signs of pancreatitis. Neither drug administration nor opportunistic infections seem to determine the increased serum pancreatic enzyme levels.

Multicenter trial on mother-to-infant transmission of GBV-C virus. The Lombardy Study Group on Vertical/Perinatal Hepatitis Viruses Transmission.

Evidence indicates that the GBV-C or hepatitis G virus can cause persistent infection in humans, but little is known on the importance of vertical transmission. To assess the risk of mother-to-infant transmission and the clinical outcome of infected babies, we investigated 175 anti-HCV positive mothers and followed-up their children for 3-33 months. GBV-C RNA was detected by RT-PCR and anti-E2 antibody was assayed by EIA. Thirty-four (19.4%) women were GBV-C RNA positive and transmission occurred to 21 (61.8%) babies; 20 (95.2%) acquired GBV-C alone, and one (4.8%) GBV-C and HCV. Maternal factors such as intravenous drug use, HIV coinfection, HCV-RNA positivity, and type of feeding were not correlated with GBV-C transmission. GBV-C RNA remained persistently positive in all infected babies but one baby who seroconverted to anti-E2. Seven (35%) babies with GBV-C alone developed marginally elevated ALT; the baby with HCV and GBV-C co-infection had the highest ALT peak value (664 IU/l). Seven of the 141 (5%) babies born to the GBV-C RNA negative mothers acquired HCV and six (85.7%) had abnormal ALT. The mean ALT peak value was significantly higher (P < 0.05) for babies with HCV than for those with GBV-C. None of the children with GBV-C or with HCV became icteric. GBV-C is frequently present in anti-HCV positive women. The infection is transmitted efficiently from mother to baby and rate of transmission is much higher than that for HCV. GBV-C can cause persistent infection in babies but usually without clear evidence of liver disease.

A prospective study on mother-to-infant transmission of hepatitis C virus.

To assess the rate of mother-to-infant transmission of hepatitis C virus (HCV) and to identify potential risk factors for transmission, we followed up (mean 22.4 months, range 1-7.5 years) a cohort of 291 babies born to anti-HCV-positive mothers, 40 of whom were also HIV coinfected. Seventeen (5.8%) babies acquired HCV infection, but none became icteric. All babies developed chronic HCV infection with 16 babies showing elevated levels of ALT. The rate of transmission was higher in babies born to mothers coinfected with HIV than in those born to mothers with HCV alone (22.5 vs. 3.2%, p < 0.0001). No association was seen between a specific maternal HCV genotype and an increased risk of neonatal infection. The median level of HCV-RNA was higher in mothers who transmitted infection than in those who did not, although the ranges overlapped. In this study, maternal history of chronic liver disease, mode of delivery and type of feeding were not predictive of HCV infection.

Effects of transdermal nitroglycerin on left ventricular function after acute myocardial infarction.

Progressive left ventricular dysfunction in acute myocardial infarction patients is associated with a poor prognosis. It has been shown that some therapeutic measures which have the potential for limiting the infarct size and preserving ventricular function, are also able to reduce the incidence of congestive heart and improve survival. The aim of this protocol was to assess the effects of transdermal nitroglycerin administered within 72 hours after the onset of acute myocardial infarction and for the following 6 months, on left ventricular function. A total of 98 consecutive acute myocardial infarction patients were randomly allocated, within 72 hours of onset of symptoms, to a double-blind 6-month-therapy with either 10 mg/24 hour transdermal nitroglycerin or placebo. Patients underwent two-dimensional echocardiography at entry, after 2 weeks, 3 months and 6 months. In the nitroglycerin group, end-diastolic volume increased during the follow-up (+6.7%, p < 0.05) while end-systolic volume remained nearly unchanged; ejection fraction and stroke volume increased progressively (+6.3%, p < 0.05, +14.2%, p < 0.05, respectively) and a important reduction of percent of dyssynergic segments was present (-19.2%, p < 0.005). In the placebo group end-diastolic volume and end-systolic volume slightly increased during the follow-up (+2% and +4.9% respectively); ejection fraction and stroke volume remained nearly unchanged during the study; percent of dyssynergic segments showed an important decrease after 2 weeks and 6 months (-21.3%, p < 0.005). A clinically relevant increase (> 20%) in ejection fraction was present more frequently in the nitroglycerin than in the placebo group (p < 0.001). In conclusion, the early (within 72 hours) and prolonged (6 months) administration of transdermal nitroglycerin in acute myocardial infarction improves ejection fraction and stroke volume but does not modify ventricular remodeling.

Trace elements and vitamins in immunomodulation in infancy and childhood.

It has been established that there is a strict and cyclical relationship between infection, immune function and nutritional status with changes in one influencing the other two. Impairment of immune function can occur even in healthy subjects in apparently good nutritional status as a consequence of some nutrient deficiencies. The impact of trace elements and vitamins on immune function are briefly reviewed.