Results of the validation study of the Psodisk instrument, and determination of the cut-off scores for varying degrees of impairment.

BACKGROUND: The Psodisk is a 10-item visual instrument, aimed at measuring the burden of psoriasis on patients. OBJECTIVES: To validate the Psodisk in a large sample of patients with psoriasis, and to define categories for the interpretation of the scores. METHODS: Data were collected in 21 dermatological centres. The Psodisk was administered at baseline (t0), after 2 or 3 days (t1) and about 3 months (t2) after baseline, and data were used to assess validity and reliability of the instrument. The cut-off scores were determined using the perception of the severity of the disease by the patient as anchor point. RESULTS: The evaluable population consisted of 320 patients at baseline, with a mean Psodisk score of 36.9. The concurrent validity of the instrument was confirmed by the high correlation with Skindex-29 and DLQI. Factor analyses selected a single factor, which alone explained almost 60% of the variance. Cronbach's coefficient alpha was 0.927, suggesting a good reliability. Test-retest reliability was verified by a Pearson's correlation coefficient between the Psodisk scores at baseline and t1 of 0.924. Five categories of disease burden were defined: 1. minimal (<9); 2. mild (9-15); 3. moderate (16-30); 4. marked (31-50); 5. severe (>50). CONCLUSION: The Psodisk showed good psychometric properties. The definition of the cut-off scores will be useful to evaluate the burden of psoriasis on patients.

The impact of psoriasis on work-related problems: a multicenter cross-sectional survey.

BACKGROUND: Psoriasis can have cumulative physical and psychosocial effects preventing sufferers from achieving their full-life potential. Few studies have addressed the impact of psoriasis on work-related characteristics. OBJECTIVE: To evaluate the impact of psoriasis on education prospects and work limitations in patients with moderate-to-severe psoriasis. METHODS: This study was conducted in 29 dermatology centres across Italy. Information was collected by questionnaire during office visits. RESULTS: A total of 787 patients (64% male, aged 50 years) completed the questionnaire. At the time of the survey, mean Psoriasis Area and Severity Index (PASI) score and disease duration were 10 and 19 years respectively. Current smokers had higher PASI scores compared to non-smokers (10.8 vs. 9.4, P = 0.02). Plaque psoriasis was the most frequently described (91.2%). Fifty-five percent of patients had limited expectations of career progression. Similarly, in 42% of cases, psoriasis reduced the prospects of improvement in employment status and 35% of patients reported having reduced earning potential. Approximately 60% of patients reported that psoriasis localized to their hands or feet caused work limitations, whilst in about 25%, it caused them to quit their job. Approximately 37% of patients reported having lost between 3-10 work days in the past 3 months due to clinical assessment or treatment. Logistic regression revealed that gender, low standard of education, number of localizations, shame, anger and self-esteem were predictors significantly associated with limitations in work. CONCLUSIONS: Moderate-to-severe psoriasis has a profound negative impact on the employment capacity of patients in Italy. Psoriasis also contributes to days lost from work, affects job opportunity, career prospects and revenue potential.

Respiratory syncytial virus induces interleukin-10 by human alveolar macrophages. Suppression of early cytokine production and implications for incomplete immunity.

Respiratory syncytial virus (RSV) causes repeated infections thought to be due to an ineffective immune response. We examined the hypothesis that incomplete immunity may result, in part, from RSV-infected alveolar macrophage production of IL-10 which can interfere with the production of immunoregulatory cytokines. We also assessed whether RSV induced the expression of the 2',5' oligoadenylate (2-5A)-dependent RNase L, an endoribonuclease involved in the antiviral activities of interferons. Human alveolar macrophages were exposed to medium (uninfected control), RSV, LPS, and RSV + LPS then were assessed for expression of the cytokines TNF-alpha, IL-1 beta, IL-8, IL-10, as well as 2-5A-dependent RNase L. LPS up-regulated the expression of protein and mRNA for all cytokines. RSV stimulated the protein levels of TNF-alpha, did not alter IL-1 beta, and decreased IL-8. RSV markedly stimulated protein expression of IL-10 and 2-5A-dependent RNase L. RSV had minor effects on the steady state mRNA levels of TNF-alpha, IL-1 beta, and IL-8, yet potently induced IL-10. Cells costimulated with RSV + LPS demonstrated reduced protein and mRNA levels of TNF-alpha, IL-1 beta, IL-8 but synergistically increased IL-10 levels compared to RSV- or LPS-activated cells. Kinetic analysis indicated that RSV induced a delayed and sustained increase in IL-10 transcripts. Furthermore, RSV-infected alveolar macrophage supernatants suppressed IL-1 beta and IL-8 production by LPS-stimulated alveolar macrophages as did recombinant IL-10. Anti-IL-10 neutralized these effects. These studies indicate that RSV is capable of suppressing production of early immunoregulatory cytokines through induction of IL-10 perhaps mediated by 2-5A-dependent RNase L (or other endoribonucleases) accounting for the ineffective immune response to this virus.

Gastrointestinal symptoms in infancy: a population-based prospective study.

BACKGROUND: During the first months of life, infants can suffer from many 'minor' gastroenterological disturbances. However, little is known about the frequency of these problems and the factors which predispose or facilitate their onset. AIMS: (a) To ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence of some variables on the onset of the symptoms. STUDY DESIGN AND PATIENTS: Each of the 150 paediatricians distributed throughout Italy followed 20 consecutive infants from birth to 6 months. 2879 infants (1422 f, 1457 m) concluded the study. The presence of the following symptoms was evaluated: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or during a set monthly examination. RESULTS: 1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms. Regurgitation was the most common disturbance (present in 23.1% of infants), followed by colic (20.5%), constipation (17.6%), failure to thrive (15.2%), vomiting (6%) and diarrhoea (4.1%). Low birth weight was the factor most frequently associated with the onset of gastrointestinal symptoms, followed by low gestational age. Feeding habits did not influence the onset of symptoms, with the exception of constipation, which was linked to a low frequency of breast-feeding. Ninety-three infants (3.2%) were hospitalised for one or more of the gastrointestinal symptoms which were considered. During the whole study period the type of formula-milk was changed in 60% of the infants with one or more gastrointestinal symptoms, and in 15.5% of the infants who did not suffer from any gastrointestinal troubles. CONCLUSIONS: Gastrointestinal symptoms are very common in infants during the first 6 months after birth. These symptoms required hospitalisation only in a small percentage of cases, but led to the prescription of a 'dietary' milk formula in approximately 60% of the cases. Low birth weight and low gestational age were the main factors influencing the onset of the symptoms.

Detection of Pneumocystis carinii among children with chronic respiratory disorders in the absence of HIV infection and immunodeficiency.

A nested polymerase chain reaction (PCR) assay was investigated for detection of Pneumocystis carinii in 96 respiratory tract specimens from 82 children, of whom 28 were immunocompetent but with chronic lung disorders (CLD), eight had AIDS and P. carinii pneumonia (PCP), 16 had AIDS but no respiratory symptoms, and 30 were healthy immunocompetent children. Gomori methenamine silver stain (GMS) and indirect immunofluorescence assay (IFA) were performed in parallel. Of 36 specimens from children with CLD, 12 were P. carinii PCR-positive compared to 10 positive by GMS-IFA. Of eight specimens from children with AIDS and PCP, seven were P. carinii-positive by PCR and six by GMS-IFA, and of 22 specimens from HIV-positive children without respiratory symptoms, two were positive by PCR and none by GMS-IFA. P. carinii DNA was also detected by PCR in blood samples from four children with P. carinii-positive nasopharyngeal aspirates. Specimens from healthy children were negative for P. carinii by both PCR and GMS-IFA. Of the seven children with CLD, who were P. carinii-positive, two had clinical and microbiological improvement with co-trimoxazole treatment, two improved initially but relapsed, and one had P. carinii cysts persistently in follow-up specimens despite co-trimoxazole treatment. These results suggest an association between P. carinii and exacerbations of CLD in childhood, in the absence of HIV infection or other immunodeficiency syndromes.

Prevalence of mefE, erm and tet(M) genes in Streptococcus pneumoniae strains from Central Italy.

One hundred and seventy-three Streptococcus pneumoniae strains isolated from surveillance studies conducted in daycare centres were studied. The mefE, erm and tet(M) genes were detected in 16.2, 45.1 and 47.4% of isolates respectively. Agreement between PCR results and antibiotic susceptibility patterns was 100%. Macrolide resistance was due to the presence of erm in 73.6% of strains and to the presence of mefE in the remaining 26.4%. All tetracycline resistant strains carried the tet(M) gene. erm was associated with tet(M) in 98.7% of strains, whereas no isolate carrying mefE carried tet(M). A significant association was found between mefE and serogroup 6 (P < 0.0005) and between erm and tet(M) and serogroup 19 (P < 0.00001).

Bronchoalveolar lavage studies in children without parenchymal lung disease: cellular constituents and protein levels.

We evaluated bronchoalveolar lavage fluid (BAL) for cellular constituents, concentration of total protein (TP), albumin (AL), fibronectin (FN), and hyaluronic acid (HA) in 16 children aged 2-32 months without pulmonary inflammatory or parenchymal disease to establish reference values. We compared our data to those reported in older children and in normal adult volunteers. BAL results were obtained simultaneously from the right middle lobe and the lingula. Results indicated that children younger than 3 years of age had a higher number of cells/mL than older children and adults (59.9 x 10(4) vs. 17.6 x 10(4) and 12 x 10(4)). Differential cell count revealed that the percentages of alveolar macrophages (AM), lymphocytes (LYM), and eosinophils (EOS) were similar to those obtained in older children and in adults, whereas the percentage of neutrophils (NEU) was higher in younger children (NEU 5.5 vs 1.6 and 1.2%, respectively) than in older children and adults. The latter difference was even greater in infants under 12 months of age (NEU 7.6%). The concentrations of TP, AL, FN, and HA in children's BAL samples were compared to values reported for adults. There were no differences between infants and children 13-32 months of age or normal adults. BAL fluid obtained simultaneously from the middle lobe and lingula were not significantly different. In conclusion, this is the first report on BAL values (cellular and noncellular constituents) in children younger than 3 years. The results may be used as reference values for further studies in children with parenchymal lung disease in this age group.

Analysis of expiratory pattern for monitoring bronchial obstruction in school-age children.

This study was designed to assess the validity of the percent of volume expired at tidal peak flow (dV/Vt) as an indicator of bronchial obstruction in school-age children. We analyzed 126 dV/Vt ratios and compared them with spirometric and plethysmographic results measured in 24 healthy (14 males) and 60 asthmatic (41 males) children; 42 of them underwent measurements before and after bronchial challenge with histamine. The two groups differed in resistance, forced expiratory volume in 1 sec (FEV1), and forced expiratory flows, as percents of predicted (FEV1: 94.6 +/- 2.4% in controls vs 86.7 +/- 1.6% in asthmatics; P less than 0.001). They did not differ in peak expiratory flow (PEF), forced vital capacity, functional residual capacity, measured by body plethysmography, and in dV/Vt. The dV/Vt was found to correlate with FEV1 (r = 0.58, P less than 0.001), PEF (r = 0.57, P less than 0.001), and other lung function parameters. Forty-two of the asthmatic children performed a bronchoprovocation histamine test. The fall of dV/Vt after histamine was significantly correlated (r = 0.61, P less than 0.001) with the variation in FEV1 and other lung function parameters. We conclude that dV/Vt is a good indicator of bronchial obstruction, as useful in school-age children as in adults and infants, with no need for the subject's cooperation.

Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity.

This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.

Respiratory disorders and hospitalization rates during the second RSV season in preterm infants who received palivizumab prophylaxis during their first RSV season.

This prospective study evaluated the frequency and severity of respiratory symptoms during the second respiratory syncytial virus (RSV) season in an italian cohort of preterm infants (< or = 35 weeks) who had received palivizumab prophylaxis in their first year of life (October 2004-April 2005) and who had not previously been hospitalized for RSV-induced lower respiratory tract infection (LRTI). infants were evaluated at enrolment (May-September 2005), in October/November 2005 and in April 2006. The occurrence of any respiratory episode, the rate of hospitalization for respiratory-related LRTI, total length of stay in hospital, physician-documented recurrent wheezing (>or = 3 physician-documented episodes of wheezing) and use of airway medication/antibiotics were recorded during follow-up. All infants had prior palivizumab prophylaxis during their first RSV season. In the total evaluable population (n=260), 32.3% of infants experienced at least one respiratory episode, 3.8% required short hospitalization because of LRTI, 8.5% had physician-documented recurrent wheezing, and 48.8% required airway medications/antibiotics during follow-up. in this study the rate of airway morbidity, hospitalization and physician-documented recurrent wheezing during the second RSV season was low among preterm infants who had received prior palivizumab prophylaxis.

Incidence of respiratory syncytial virus positivity in young Italian children referred to the emergency departments for lower respiratory tract infection over two consecutive epidemic seasons.

BACKGROUND: The rate and severity of respiratory syncytial virus (RSV) infections within the same nation may vary from one year to another. PATIENTS AND METHODS: The "Osservatorio VRS" study collected epidemiological data on RSV infection among Italian children aged < or = 4 years referred to emergency departments of 14 centers, for suspected lower respiratory tract infections (LRTI) in two consecutive RSV seasons (October 2000-April 2001 and October 2001-April 2002). Medical history and physical examination were recorded and an immunoenzymatic RSV test was performed on nasal secretions. Study variables were collected and evaluated separately, then compared. RESULTS: In all, 272 and 756 children were included in the two seasons, respectively, of which 31.6% and 19.2% were RSV positive (+). Children of the first season had lower gestational and chronological age, higher rates of chronic lung disease (CLD), very low birth weight (< 1,500 g), larger use of corticosteroids or bronchodilators. Main risk factors for RSV infection were a young age (< 1 year) and a low birth weight (< 1,500 g). RSV infection reached its peak in February (first season) or March (second season), with an earlier appearance in the northern and central as compared to the southern regions. Rate of hospitalization and LRTI was higher in RSV+ children, especially if young. CONCLUSION: Although rhythms of the RSV seasons and patient characteristics may vary from one year to another, the severity of RSV disease in nonprophylaxed infants and young children remains high.

[Evaluation of the effects of a nucleotide-enriched formula on the incidence of diarrhea. Italian multicenter national study]. / Valutazione degli effetti di una formula arricchita con nucleotidi sulla incidenza della diarrea. Studio multicentrico nazionale italiano.

BACKGROUND: Aim of this study is to evaluate the incidence of diarrhea in children fed with a nucleotide-supplemented formula (Similac FormulaPlus) in comparison with formula without nucleotide supplementation. METHODS: We investigated the effects of a nucleotide-supplemented formula on the incidence of diarrheal episodes in 3315 infants with a multicenter study conduced by 386 pediatricians since March 1998 until October 1999. The study population has been divided into 4 groups based on the type of feeding; group 1 (n = 958) = exclusively nucleotide-supplemented formula, group 2 (n = 824) = exclusively formula without nucleotide supplementation, group 3 (n = 920) = mixed breast-feeding and nucleotide-supplemented formula, group 4 (n = 613) = mixed breastfeeding and formula without nucleotide supplementation. At the beginning of the study the 4 groups did not differ for body weight, length and mass index. The infants were enrolled since the first month up to the end of the third month of life and they were followed-up to the end of the sixth month of life. During the period of observation the growth of lenght, weight and mass index was similar among the 4 groups. RESULTS: Monthly incidence of diarrhea was computed and the comparison between group 1 and group 2 using the summary odds-ratio of Mantel-Haenszel showed that in group 1 the incidence of diarrhea was significantly lower than un group 2 (RR = 0.567); CI 95% = 0.440-0.732); similar results were obtained comparing the incidence of diarrhea between group 3 and group 4, having the former a RR = 0.630 (CI 95% = 0.476-0.834). CONCLUSIONS: The conclusion drawn is that the supplementation with nucleotide of the formula milk decreases the risk of diarrheal episodes during the first six month of life in healthy infants. Such a positive effect is present both in exclusively nucleotide-supplemented formula and in mixed breast-feeding and nucleotide-supplemented formula fed infants. Interpretation of these results is that nucleotides, much more present in human milk than in formula milk, improve the immune defense of the infants stimulating particularly the cell-mediated immunity.

Respiratory syncytial virus replication in human lung epithelial cells: inhibition by tumor necrosis factor alpha and interferon beta.

Respiratory syncytial virus (RSV) is the major pathogen causing severe lung disease in children. RSV initially replicates efficiently in the respiratory tract but becomes undetectable by 7 to 21 d after infection in normal children, suggesting that intrinsic cellular mechanisms, as yet undefined, may restrict virus replication. To provide an in vitro model to examine mechanisms that restrict RSV replication, three human lung epithelial cell lines were exposed to RSV in vitro and virus replication proceeded in a dose- and time-dependent manner, although less efficiently than the highly permissive CV-1 cell line (monkey kidney epithelial cell). Tumor necrosis factor alpha (TNF alpha) and/or interferon beta (IFN beta) markedly inhibited RSV replication in a dose- and time-dependent manner. TNF alpha combined with IFN beta essentially aborted RSV replication in A549 epithelial cells. TNF alpha and/or IFN beta did not induce cell membrane damage, cause cell lysis, or inhibit cellular protein synthesis. RSV-infected human alveolar macrophages, which produce TNF alpha, failed to productively infect lung epithelial cells in co-culture. Together these studies suggest that endogenous TNF alpha coupled with exogenous IFN beta could restrict RSV replication in lung epithelium.

Electrophoretic investigation of L-asparaginase influence on blood and spleen blood globulins. Experimental study.

In view of detecting the influence of L-asparaginase on blood and spleen blood globulins, 42 rabbits were daily injected for three weeks with different doses of this drug. Electrophoretic analysis of blood and spleen blood samples from these animals showed no relationship between the doses used and the changes of circulating blood globulins indicating the well known immunodepressing effects of the drug. However, in the spleen blood from the inoculated rabbits (as compared with a control group) a small excess of gamma globulins which appeared especially after 1-2 weeks of daily injections with 2,000 or 10,000 I.U.L-asparaginase/kg b.w. was interpreted as due to the antigenic action of the enzymatic product administered.

L-Asparaginase: effect on 7S gamma globulin extents and germinal centers in spleen and lymph-nodes.

Administration of L-asparaginase may cause remission in a high percentage of acute lymphocytic leukemias and lymphomas, either in experimental animals or in human beings. This enzyme is able to depress immune reactions like lymphocyte blastogenesis and delayed hypersensitivity, and to impair gamma-globulin synthesis. L-asparaginase also has antigenic properties, and may cause the formation of anti-L-asparaginase antibodies. This study reports observations on the effect of L-asparginase on the 7S gamma-globulin levels and on the behaviour of the germinal centers in spleen and lymph nodes. It has been found that after administration of low or intermediate doses of L-asparginase, a decrease in the size of the follicular marginal zones occurred. This was accompanied by an enlargement of the germinal centers. Furthermore the spleen weight decreased and the concentration of 7S gamma-globulin diminished slightly. In animals given high doses of L-asparaginase, germinal centers were enlarged even more but marginal zones appeared repopulated although not to the degree of the controls. The spleen weight of these enzyme-injected animals reached almost the normal values, while a statistically significant decrease of 7S gamma-globulin concentrations was found.

Respiratory syncytial virus lung infection in infants: immunoregulatory role of infected alveolar macrophages.

Thirteen previously healthy children with acute onset of severe lower respiratory tract signs and symptoms underwent bronchoscopy and bronchoalveolar lavage (BAL) for diagnostic purposes. BAL samples were assessed for viral, bacterial, mycobacterial, and fungal cultures. Cytospin preparations of BAL cells were assessed for expression of respiratory syncytial virus (RSV), HLA-DR, interleukin-1 beta, and tumor necrosis factor proteins. Purified alveolar macrophages from 2 RSV-infected children were assessed for viral replication. Three children had bacterial pneumonia and 6 were infected with RSV. BAL cells from RSV-infected children demonstrated viral protein expression. Alveolar macrophages were the predominant cell type recovered by BAL and demonstrated coexpression of RSV, HLA-DR, interleukin-1 beta, and tumor necrosis factor proteins. Purified alveolar macrophages from 2 RSV-infected children replicated RSV by infectious center assays. Thus, alveolar macrophages are infected by RSV in vivo and coexpress potent immunomodulatory molecules that potentially regulate the local immune response or lung injury due to this virus.

Restricted replication of respiratory syncytial virus in human alveolar macrophages.

The cellular factors that regulate infection and replication of respiratory syncytial virus (RSV) in human alveolar macrophages were examined. RSV-exposed alveolar macrophages demonstrated a time-dependent expression of viral glycoproteins, maximal by 24 h post-infection resulting in infection of approx. 38% of the cells. Essentially all (33%) of these freshly isolated alveolar macrophages replicated RSV as shown by infectious centre assays. This RSV-permissive subpopulation of alveolar macrophages consisted primarily of major histocompatibility class II-expressing cells as determined by fluorescence-activated cell sorting. Re-infection of alveolar macrophages did not significantly alter the number of cells infected or capable of replicating RSV. However, in vitro differentiation of alveolar macrophages prior to infection resulted in a significant (P < 0.05), time-dependent decrease (approx. sevenfold) in the number of cells that replicated virus. The mechanism by which cellular differentiation restricted RSV replication is unknown. Production of defective interfering particles did not account for this decrease. Alveolar macrophages infected with RSV produce a variety of cytokines potentially contributing to this restricted viral replication. Pretreatment with several of these cytokines did not affect viral infection or replication. However, tumour necrosis factor (TNF alpha) significantly (P < 0.05) decreased viral replication but only by 30 to 60%. Thus RSV replication is reduced by in vitro differentiation of alveolar macrophages and, to a lesser degree, by pretreatment with TNF.