Tuberculosis infection and disease in immigrant children

From the second half of the eighties, the cases of tuberculosis (TBC) in Italy have been constantly increasing. The increase in TBC cases in developed countries is related to different factors, including HIV epidemic and increased number of immigrants from countries with high TBC incidence and important socio-economic problems. Compared with adults few children with TBC were homeless or coinfected with HIV, nonetheless the children lived frequently in low socioeconomic status and consequently high risk of being uninsured and with adults at risk for tuberculosis (immediate relative, household members, or recently immigrated). An epidemiologic study was carried out, in order to evaluate the impact of TBC infection in immigrant children. From January 2001 to December 2002, Mantoux test (5 IU) was performed in immigrant children hospitalized or followed in two children hospitals. They included 228 children: mean age 4 years (range 1 month to 15 years). The patients came from: South America (44%) (especially from Ecuador), from Africa (20%), from Eastern Europe (19%), (especially from Middle East and North Africa), from Far East (17%). In 30 cases (13,2%) Mantoux test was positive. Among these latter, 21 presented latent infection, whereas another 9 had tuberculous disease with pulmonary localization and one of them associated with cervical adenopathy. In the study period, among all children (4426) admitted the two Units, the prevalence of tuberculous disease was 2,5% in immigrant children compared 0.2% in native children. Accurate epidemiologic monitoring, further clinical studies aimed at highlighting TBC peculiar aspects in children, and adequate therapy can lead to TBC control in the immigrant children.     

T lymphocytes in children with recurrent respiratory infections: effect of the use of thymostimulin on the alterations of T-cell subsets

OKT3-, OKT4- and OKT8-positive cells were estimated in 303 children with recurrent respiratory infections. The patients (selected by a score method) had experienced 13 or more infections a year. Modifications in T-cell subsets were observed in 154 patients (50.8%). Decreased OKT3- and OKT4-positive cells were present in 80 children (26.4%), while 74 patients (24.4%) showed normal values of OKT3-positive cells but decreased OKT4- and increased OKT8-positive cells. An attempt at treatment with thymostimulin was undertaken in a group of randomly chosen children with modifications in T-cell subsets. The use of thymostimulin induced the treated children more readily than the untreated ones to show improvement in both the score for respiratory infections and the distribution of T-cell subsets.     

Human basophil releasability. I. Age-related changes in basophil releasability

Releasability of human basophils (i.e., the response to a standard stimulus) is an important parameter in several pathophysiologic conditions. We studied the IgE (anti-IgE)- and non-IgE-mediated (f-met peptide and Ca2+ ionophore A23187) releasability of human basophils obtained from 63 normal donors whose ages ranged from 1 to 86 years. The maximum percent of histamine release induced by anti-IgE was significantly correlated (rs = 0.57; p less than 0.001) with the age of donors. The sensitivity to a standard concentration of anti-IgE (3 X 10(-2) mcg/ml) was also correlated with the age of cell donors (rs = 0.68; p less than 0.001). In the population of 63 donors tested, the maximum percent of histamine release and the cell sensitivity to anti-IgE appeared to be independent of the serum concentration of IgE. However, we found a positive correlation (rs = 0.55; p less than 0.05) between serum IgE level and anti-IgE-induced histamine release in the group less than 20 years of age. In contrast, a negative correlation (rs = -0.32; p less than 0.05) between serum IgE level and anti-IgE-induced histamine secretion was found in the group greater than 21 years of age. The maximum percent of histamine release induced by f-met peptide and Ca2+ ionophore A23187 appeared to be independent to both the age of the donors and the serum IgE level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic and cardiovascular risk factors in Klinefelter syndrome

Klinefelter syndrome (KS), which normally presents with a 47,XXY karyotype, is the most common sex chromosome disorder in males. It is also the most common genetic cause of male infertility. KS subjects are typically tall, with small and firm testes, gynecomastia, broad hips, and sparse body hair, although a less evident presentation is also possible. KS is also characterized by a high prevalence of hypogonadism, metabolic syndrome (MetS) and cardiovascular disease. The aim of this article is to systematically review metabolic and the cardiovascular risk factors in KS patients. Hypogonadism has an important role in the pathogenesis of the changes in body composition (particularly visceral obesity) and hence of insulin resistance and MetS, but the association between KS and MetS may go beyond hypogonadism alone. From childhood, KS patients may show an increase in visceral fat with a reduction in lean body mass and an increase in glucose and impaired fat metabolism. Their increased incidence of congenital anomalies, epicardial adipose tissue, and thromboembolic disease suggests they have a higher risk of cardiovascular disease. There is conflicting evidence on the effects of testosterone therapy on body composition and metabolism.     

Germline mutations and new copy number variants among 40 pediatric cancer patients suspected for genetic predisposition

Cancer predisposition syndromes (CPS) result from germline pathogenic variants, and they are increasingly recognized in the etiology of many pediatric cancers. Herein, we report the genetic/genomic analysis of 40 pediatric patients enrolled from 2016 to 2018. Our diagnostic workflow was successful in 50% of screened cases. Overall, the proportion of CPS in our case series is 10.9% (20/184) of enrolled patients. Interestingly, 12.5% of patients achieved a conclusive diagnosis through the analysis of chromosomal imbalance. Indeed, we observed germline microdeletions/duplications of regions encompassing cancer-related genes in 50% of patients undergoing array-CGH: EIF3H duplication in a patient with infantile desmoplastic astrocytoma and low-grade Glioma; SLFN11 deletion, SOX4 duplication, and PARK2 partial deletion in three neuroblastoma patients; a PTPRD partial deletion in a child diagnosed with glioblastoma multiforme. Finally, we identified two cases due to DICER1 germline mutations.     

Epidemiological and Environmental Investigations of Legionella pneumophila Infection in Cattle and Case Report of Fatal Pneumonia in a Calf

A fatal pneumonia due to Legionella pneumophila was diagnosed in a young calf reared in a dairy herd located in northern Italy. Clinical symptoms consisted of watery diarrhea, hyperthermia, anorexia, and severe dyspnea. The pathological and histological findings were very similar to those observed in human legionellosis. Legionella pneumophila serogroup 1 (SG1) and SG10 were isolated from the calf’s lung, and L. pneumophila SG1 was isolated from the calf’s liver. L. pneumophila SG1 was also demonstrated in the lung tissue by immunofluorescence and immunohistochemical examinations. Nine of 10 L. pneumophila SG1 isolates belonged to the Olda subtype, and 1 belonged to the Camperdown subtype. A very low prevalence of antibodies to Legionella was detected in cows and calves reared in the same herd. Cultures of aqueous sediment of an old electric water heater which supplied hot water for the feeding of the calves yielded L. pneumophila SG1. Four of the colonies tested belonged to the Olda subtype. Ten clinical and four environmental isolates were examined for the presence of plasmids. Nine of them were also examined by pulsed-field gel electrophoresis assay, and the same patterns were found for L. pneumophila SG1 Olda strains isolated from the calf and from the electric heater. This is the first report of a documented case of a naturally occurring Legionella pneumonia in an animal. Cattle probably act as accidental hosts for legionellae, much the same as humans.     

Circulating E-Selectin Levels in Chronic Hepatitis C Patients with Normal or Elevated Transaminase Before and After Alpha-Interferon Treatment

E-selectin, an adhesion molecule of the selectin family, is involved in leukocyte adhesion to the endothelium and in the cellular immunological reactions. Expression of this molecule, in fact, is physiologically absent, but it becomes evident on sinusoidal lining cells during inflammatory liver disease. The aim of this study was to evaluate the behavior of E-selectin in chronic hepatitis C (CH-C) patients with persistently normal transaminase in comparison to patients with CH-C and elevated transaminase, and its changes during alpha-interferon therapy. Immunohistochemical localization of E-selectin was also performed on liver tissue specimens of both groups. Fifty-eight subjects were divided into 3 groups: group A included 18 patients with CH-C and persistently normal transaminase; group B 20 patients with CH-C and persistently elevated transaminase levels and group C included 20 healthy subjects, representing the control group. The first two groups were treated with r-IFN at a dose of 6 MU 3 times a week for 3 months and followed-up with 3 MU 3 times a week for another 3 months. Serum baseline values of E-selectin in groups A and B were significantly higher than those in group C (P < 0.04), but there was no difference between groups A and B. Furthermore, there was a trend toward higher E-selectin values as histological severity increased (r = 0.69; P < 0.0001). Post-treatment E-selectin serum values showed a moderate decrease in both groups, but only among responder patients; while E-selectin levels were unchanged in non responders. Immunohistochemical localization showed no staining for E-selectin in normal liver specimens, while there was a quite similar staining for E-selectin in the two groups of patients. In conclusion, this study shows that serum E-selectin levels in patients with CH-C and persistently normal transaminase are higher than in controls and they are associated with severity of liver disease. Liver of these patients express E-selectin molecules, suggesting an activation of the immune system almost identical to that of patients with CH-C and elevated transaminase. In both groups only responder patients showed a moderate decrease below baseline serum values.     

Neonatal hypothyroidism induces striatal dopaminergic dysfunction

Oral administration of the antithyroid drug methimazole (50 mg/kg per day) to rats during the last six days of pregnancy, and subsequent daily s.c. injection of methimazole (20-30 mg/kg) to their pups from birth to postnatal day 30 provoked hormonal and somatic alterations resembling (with all caution to any association between rodent and human data) those of congenital hypothyroidism. The steady-state concentrations of striatal dopamine were similar in hypothyroid and euthyroid, 32-day-old rats, while the levels of the dopamine metabolites 3,4-dihydroxyphenylacetic and homovanillic acids were markedly decreased in hypothyroidism. The results of this and our earlier study [Vaccari A. and Gessa G. L. (1989) Neurochem. Res. 14, 949-955] show that the maximal synaptosomal uptake of [3H]dopamine, an index for the density of nigrostriatal dopaminergic terminals, and the maximum number of membrane [3H]tyramine binding sites, reflecting the concentration of the vesicular transporter for dopamine, were decreased in the hypothyroid striatum. There was also a loss of those D1-type dopaminergic receptors claimed to be located on neurons intrinsic to the striatum, and, consequently, dopamine-stimulated, D1-regulated adenylate cyclase activity was depressed. It is suggested that individual dopaminergic nerve endings in the neonatal hypothyroid striatum must contain more dopamine, owing to some loss of pertinent innervation and, therefore, to the presence of less vesicular transport sites for dopamine. Hypothyroidism-related decreases in the maximum number of striatal D1- and, reportedly, D2-receptors, plus the impairment of D1-coupled second messenger activity, may play a role in the derangement of those neurobehavioural patterns where a dopaminergic regulation is putatively implied.     

Mechanisms of uterine specificity of vaginal progesterone

Endometrial transformations achieved by vaginal progesterone exceed those normally expected from the circulating concentrations obtained, this suggests some degree of direct vagina to uterus transport. We speculate on the different mechanisms involved in uterine specificity of vaginal progesterone and report data of a preliminary randomized study comparing progesterone concentrations in serum and endometrial tissue obtained from hysterectomy specimens after vaginal or i.m. administration. Eight post-menopausal women undergoing transabdominal hysterectomy were randomized to receive either vaginal progesterone gel, 90 mg, or i.m. progesterone formulation, 50 mg, at 08.00 and 20.00 on the day before surgery and at 06.00 on the day of surgery. Venous blood samples for progesterone measurement were drawn at 08.00 on the day before surgery and during the surgery. Endometrial progesterone concentrations were markedly higher in women who received vaginal progesterone (1.38+/-0.66 and 0.38+/-0.19 ng/mg protein, for vaginal and i.m. groups respectively) (P < 0.02) despite lower serum concentrations (4.17 < 0.56 and 32.32+/-11.06 ng/ml, for vaginal and i.m. groups respectively) (P < 0.001). The vaginal route induces endometrial progesterone concentrations that far exceed those expected from the serum progesterone concentrations achieved.     

Clinical,immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study

A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and 0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively. For the 9 patients who developed CLD during follow-up, the duration of follow-up, rather than age at diagnosis; previous administration of intramuscular immunoglobulin; and residual IgG levels had a significant effect on the development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15 already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and meningitis/meningoencephalitis decreased over follow-up, probably due to optimal protection provided by high circulating IgG levels reached with IVIG.