Effects of repeated low-dose exposure of the nerve agent VX on monoamine levels in different brain structures in mice.

In a previous report, alterations of the serotonin metabolism were previously reported in mice intoxicated with repeated low doses of soman. In order to better understand the effects induced by repeated low-dose exposure to organophosphorus compounds on physiological and behavioural functions, the levels of endogenous monoamines (serotonin and dopamine) in different brain areas in mice intoxicated with sublethal dose of (O-ethyl-S-[2(di-isopropylamino) ethyl] methyl phosphonothioate) (VX) were analysed by HPLC method with electrochemical detection. Animals were injected once a day for three consecutive days with 0.10 LD50 of VX (5 µg/kg, i.p). Neither severe signs of cholinergic toxicity nor pathological changes in brain tissue of exposed animals were observed. Cholinesterase (ChE) activity was only inhibited in plasma (a maximum of 30% inhibition 24 h after the last injection of VX), but remained unchanged in the brain. Serotonin and dopamine (DA) metabolism appeared significantly modified. During the entire period of investigation, at least one of the three parameters investigated (i.e. DA and DOPAC levels and DOPAC/DA ratio) was modified. During the toxic challenge, an increase of the serotonin metabolism was noted in hippocampus (HPC), hypothalamus/thalamus, pons medulla and cerebellum (CER). This increase was maintained 4 weeks after exposure in HPC, pons medulla and CER whereas a decrease in cortex 3 weeks after the toxic challenge was observed. The lack of correlation between brain ChE activity and neurochemical outcomes points out to independent mechanisms. The involvement in possibly long-lasting behavioural disorders is discussed.

Novel treatments of asthma and allergic diseases.

The prevalence of allergic diseases has considerably increased, mostly in industrialized countries (> 20%), and asthma affects approximately 300 million individuals worldwide. Current therapies are able to control symptoms although they do not modulate immunological dysregulation that characterizes allergic diseases. Over the last 30 years, only a few new drugs have been introduced on the market and they all act on Th2-type response which has a critical role in the pathogenesis of allergic diseases. Recently, a new scenario has been opened on Th17-cells, Th1-type cytokines and innate immune system components involved in the inflammatory pathogenesis of asthma and other allergic diseases. These findings suggest a promising therapeutic role of new agents that block the action of specific cytokines. Furthermore, the concept of an intrinsic structural defect in the bronchial epithelium paves the way to innovative therapeutic strategies. In this review we present an update on therapies for allergic diseases with special focus on asthma.

Immune responses to tetanus vaccination in Italian healthy subjects and children with recurrent infections.

The ability of vaccine antigen to generate protection is a challenge that cannot be restricted to the antibody response; however, the contribution of T cell-mediated mechanisms has not been extensively analyzed. Age and administration to specific categories of patients, i.e. children with recurrent infections (RI), are some of the factors that might affect the vaccine immune response. We investigated the humoral and cellular response to tetanus toxoid (TT) vaccine in 104 healthy children (HC), 11 newborns and 22 healthy adults to characterize the status of immunity according to age and compared it to 118 RI children. Humoral and cellular responses varied in both groups according to age and doses of TT administered. The prevalence of antibody and cellular response was similar in both cohorts (HC 88 percent and 82 percent versus RI 86 percent and 85 percent), however, TT antibody values were significantly higher in 12-18 months old RI children compared to HC (median: 5 IU/ml vs 1.10 IU/ml) (p = 0.02). The lack of an efficient immune response was observed in 12-15 percent of children from both cohorts. Our data showed that specific antibodies were responsible for early protection, whereas cell-mediated mechanisms may contribute to the generation of long-term immunity after an appropriate vaccine recall. The occurrence of higher TT antibody values in 12-18 months old RI children deserves additional research to determine whether they are caused by different infectious agents and/or by other environmental factors. Clarification of this issue is important for categorizing patients into an optimal vaccine policy.

Anti-infective prophylaxis for primary immunodeficiencies: what is done in Italian Primary Immunodeficiency Network centers (IPINet) and review of the literature.

Primary immunodeficiencies (PIDs) are rare diseases characterized by an increased susceptibility to infections. Early diagnosis and appropriate treatment are critical for reducing morbidity and mortality. Based on available data, the efficacy of antibiotic administration for the prophylaxis of infections remains uncertain, and recommendations supporting this practice are poor. The use of antimicrobial prophylaxis is mainly based on single institution-specific experience without controlled measurements of patient safety and quality health outcomes. To address this issue an Italian Network on Primary Immunodeficiencies (IPINet) has been set up in 1999 within the Italian Association of Pediatric Hematology and Oncology (AIEOP) to increase the awareness of these disorders among physicians. Further, diagnostic and treatment guideline recommendations have been established to standardize the best clinical assistance to all patients, including antibiotic prophylaxis, and for a national epidemiologic monitoring of PIDs. The aim of this review is not only to give a scientific update on the use of antimicrobial prophylaxis in selected congenital immunological disorders but also to draw a picture of this practice in the context of the Italian Primary Immunodeficiency Network (IPINet). Controlled multicenter studies are necessary to establish if, when and how you should start an efficacious antimicrobial prophylaxis.

The impact of TACI mutations: from hypogammaglobulinemia in infancy to autoimmunity in adulthood.

Common variable immunodeficiency (CVID) is considered the most common symptomatic antibody deficiency and, although mainly reported in adults, it may present from childhood. Few data on the impact of TACI defects on the clinical and immunological status of children are available. We screened 42 hypogammaglobulinemic children to investigate the frequency and mutational features of TACI defects. The genetic, clinical and immunological characterization was extended to 31 relatives of 11 children with TACI mutations. Of interest, our analysis showed a considerably higher mutation frequency in hypogammaglobulinemic children (13/42; 31%) than in other cohorts of adult patients. In seven out of nine families with the C104R variant, the prevalence of autoimmunity was significantly higher in C104R heterozygous relatives (8/15; 53%) than in those with no C104R mutation (1/11; 9%). Our data suggest a different impact of TACI mutations, from hypogammaglobulinemia in children to autoimmune disease in adulthood.

Uptake by breast carcinoma of a lipidic nanoemulsion after intralesional injection into the patients: a new strategy for neoadjuvant chemotherapy.

OBJECTIVE: Previously we showed that after intravenous injection a lipidic nanoemulsion concentrates in breast carcinoma tissue and other solid tumors and may carry drugs directed against neoplastic tissues. Use of the nanoemulsion decreases toxicity of the chemotherapeutic agents without decreasing the anticancer action. Currently, the hypothesis was tested whether the nanoemulsion concentrates in breast carcinoma tissue after locoregional injection. METHODS: Three different techniques of injection of the nanoemulsion were tested in patients scheduled for surgical treatment: G1 (n=4) into the mammary tissue 5 cm away from the tumor; G2 (n=4) into the peritumoral mammary tissue; G3 (n=6) into the tumoral tissue. The nanoemulsion labeled with radioactive cholesteryl oleate was injected 12 h before surgery; plasma decay of the label was determined from blood samples collected over 24 h and the tissue fragments excised during the surgery were analyzed for radioactivity uptake. RESULTS: Among the three nanoemulsion injection techniques, G3 showed the greatest uptake (data expressed in c.p.m/g of tissue) by the tumor (44,769+/-54,749) and by the lymph node (2356+/-2966), as well as the greatest concentration in tumor compared to normal tissue (844+/-1673). In G1 and G2, uptakes were, respectively, tumor: 60+/-71 and 843+/-1526; lymph node: 263+/-375 and 102+/-74; normal tissue: 139+/-102 and 217+/-413. CONCLUSIONS: Therefore, with intralesional injection of the nanoemulsion, a great concentration effect can be achieved. This injection technique may be thus a promising approach for drug-targeting in neoadjuvant chemotherapy in breast cancer treatment.

A prospective study on children with initial diagnosis of transient hypogammaglobulinemia of infancy: results from the Italian Primary Immunodeficiency Network.

Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder characterized by reduced serum IgG levels in early infancy. A putative diagnosis is initially made after exclusion of other causes of hypogammaglobulinemia while a definitive diagnosis of THI can only be made a posteriori in patients with normalization of IgG levels. The aim of this study is to characterize clinical and immunological features of children with an initial diagnosis of THI in correlation to natural outcome, and to assess predictive laboratory parameters of clinical evolution for this disorder. We prospectively analysed clinical and immunological characteristics of 77 THI children at initial diagnosis and of 57 patients at follow-up. Memory B cell subsets and in vitro immunoglobulin production were evaluated. Seventy patients (91 percent) showed clinical symptoms. Patients suffered from infections (91 percent), allergies (47 percent) and autoimmune disease (4 percent). During follow-up 41/57 children (72 percent) normalized IgG values, mostly within 24 months of age (p less than 0.001), allowing the diagnosis of THI. The 16 children who did not normalize their IgG levels showed a higher frequency of severe infections and autoimmune disease (p less than 0.01). Moreover, they expressed a reduced frequency of IgM and switched memory B cells (p less than 0.01) and an inability to produce IgG in vitro (p less than 0.02). We conclude that most patients with an initial diagnosis of THI spontaneously recover within 24 months of age and have a benign clinical course, while a subgroup of children with undefined hypogammaglobulinemia share a clinical and immunological profile with other primary immunodeficiencies. Early recognition of children with hypogammaglobulinemia during infancy who are likely to suffer from permanent immunodeficiencies later in life would allow prompt and appropriate laboratory and clinical interventions.

Happy Air: a school-based educational program to maximize detection of asthma in children.

OBJECTIVE: To investigate whether an active partnership among school, parents, and pediatricians allows early identification and treatment of asthmatic children. METHODS: An asthma educational program (Happy Air), based on a strong family-physician-school interrelationship, was performed in six primary schools (2,765 children) before administering a screening questionnaire to the parents. RESULTS: A high response rate (96%) demonstrated 2,649 responders available for the asthma screening: 135 children (5%) received a diagnosis of asthma, of which 37 (27%) were recognized de novo. CONCLUSION: The active participation of school and parents is the determining factor for the success of an asthma screening program.

[Back school project in a company: how to prevent low back pain]. / Progetto back school in azienda: come prevenire il mal di schiena.

This study refers to the experience of Back School training which was performed inside the Fire Brigade Department of the multicompany Petrochemical Plant of Ferrara. Our project includes integrated activities that promote employee's well-being related to their workplace and their work duties with the intention of improving how the organization runs. This project has been carried out in cooperation with the Reahabilitation Medicine Department "S. Giorgio" of Arcispedale S. Anna in Ferrara.

The effect of education on dementia occurrence in an Italian population with middle to high socioeconomic status.

OBJECTIVE: To explore the relation between education and dementia prevalence by computing the odds ratios (ORs) for different educational levels after adjustment for age, gender, occupational level, and life habits. METHODS: A two-phase community study including 495 elderly subjects with middle to high socioeconomic status, aged more than 60 years and with a high percentage of noneducated subjects, was carried out in the province of Ravenna, Italy. Dementia and dementia type were clinically diagnosed using DSM-III-R diagnostic criteria. RESULTS: A higher prevalence of dementia was observed among noneducated subjects of both genders. Comparing no education with any education, the OR (adjusted for age, gender, and occupation) was 4.7 (95% CI = 2.3 to 9.6). The association, although present in all age groups, was extraordinarily strong among the youngest subjects (61 to 69 years) (OR = 139.5, 95% CI = 6.4 to 3,024.6) and decreased with increasing age. Life habits, such as smoking and alcohol consumption as well as current or previous history of hypertension, did not change the results. There was no significant difference in dementia prevalence among less well-educated (up to 3 years of education) and better-educated subjects (more than 3 years of schooling) after age and gender were taken into account. Similar findings were found for Alzheimer's disease and vascular dementia separately. CONCLUSIONS: Having no education is associated with dementia independent of gender, occupation, life habits, and hypertension. This association was stronger among younger old persons, and decreased with increasing age. The findings suggest that the first decade of life is a critical period for developing dementia later in life. The decrease in dementia risk may be due to schooling, according to the cerebral reserve hypothesis, or to other factors associated with a higher educational level during childhood.

Respiratory quotient changes in full term newborn infants within 30 hours from birth before start of milk feeding.

OBJECTIVE: To evaluate substrate utilization in full-term newborn infants, fed every 3-4 h with glucose 10% solution, within 30 h from birth. DESIGN: Random. SETTING: Full term newborn infants at the Paediatric Division City Major Hospital, Chair of Paediatrics, Verona University. SUBJECTS: Forty-six newborn infants, 24 females and 22 males of 39+/-2 weeks gestational age. METHODS: Oxygen consumption (VO2) and CO2 production (VCO2) were measured. Permitting the computation of the respiratory quotient (RQ), which expresses substrate oxidation, at 6 and 30 h from birth. An indirect calorimeter (Deltratrac TMII-MBM-200-DATEX) was used to measure components of energy-balance. RESULTS: Energy expenditure calculated at 6 h was 8.130 (+/-1.5757) kJ/kg/h. At 30 h the value changed to 8.858 (+/-1.483) kJ/kg/h. Statistical evaluation (t-student) showed a significant (P=0.000) variation in RQ values (6 h: RQ=0.94; 30 h: R=0.88). CONCLUSIONS: Respiratory quotient suggests an increase of energy derived from fat metabolism at 30 h from birth. Our data confirm that early breast feeding or formula milk feeding could represent a physiological approach to nutritional regimen of the newborn infant.

Pulmonary valve origin of pedunculated rhabdomyoma causing moderate right ventricular outflow obstruction: surgical-implications.

A rare case of single, pedunculated, ball-like rhabdomyoma of the pulmonary valve, causing moderate right ventricular outflow obstruction in an infant with tuberous sclerosis, is presented. The diagnostic and surgical implications are discussed.

Renal-portal shunt to restore normal reninism and blood pressure in experimental renovascular hypertension in dogs.

The role of the liver in the metabolism of renin was evaluated in dogs with high plasma renin and hypertension due to experimental bilateral renal artery stenosis. Ten adult dogs were studied in three consecutive phases: (1) basal conditions, (2) with bilateral ischemic kidneys, and (3) after derivation of renal vein blood into the portal system. Secretion, total clearance, hepatic clearance, and hapatic extraction of renin were estimated in each phase by measuring plasma renin activity (PRA) in blood collected simultaneously from arteries, inferior vena cava, vena porta, hepatic and renal veins, and by determining renal and hepatic blood flow. Blood pressure was measured by intra-arterial catheterization. The results demonstrated an increase in the hepatic metabolism of renin when the hyper-reninemic patterns of renal blood directly perfused the liver. Under these conditions, hepatic and circulating renin fell to basal values and blood pressure returned to normal.

[Criteria of surgical treatment in 148 cases of recto-sigmoid cancer]. / Criteri di terapia chirurgica su 148 casi di cancro del retto-sigma.

The clinical aspects of cancer of the rectum and sigmoid colon are discussed, and stress is laid on the importance of symptomatological, radiological and endoscopical examination, including biopsy. A description is given of the surgical criteria employed in 148 cases, with particular attention to the indications for anterior resection of the rectum and abdominoperineal amputation of the rectum according to Miles.

[Surprise in the hernia sac: the intrasaccular tumor of the sigma]. / Sorprese nel sacco erniario: il tumore intrasacculare del sigma.

In this report we define the terms of saccular, extra-saccular and intrasaccular tumor and present a rare case of intrasaccular tumor of the colon; it is remarked a careful clinical examination of patients with inguinal hernias to find a colon tumor; diagnosis in emergency is intra-operative. Two therapeutics options are possible: the simultaneous treatment or the delayed resolution.

[Intestinal enterolithiasis]. / Enterolitiasi intestinale.

We present a case report of a patient affected by chronic ileitis re-made acute and in which we found some entheroliths; they wern't not bezoars. We remarked the importance in bowel diseases in which are stasis or ipomotility like the Crohns disease. Sometimes they are responsible of subsequent complications like obstructions, hemorrages, perforations and so their presence must be considered by important diagnostic implications.