Reliability of toxicokinetic modelling for PFAS exposure assessment in contaminated water in northern Italy.

Introduction: Long-term contamination of tap water and groundwater by perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been documented in the Veneto region of northern Italy. This study aimed to assess the exposure of individuals residing in the contaminated area and to test several toxicokinetic (TK) models of varying complexities to identify an efficient method for predicting perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) concentrations in human serum using observed data.The ultimate goal is to provide public health officials with guidance on selecting the appropriate TK model for specific contexts, a reliable and rapid tool to support human bio-monitoring (HBM) studies. Methods: Two simpler empirical TK models and a more complex multi-compartment physiologically based toxicokinetic (PBTK) model were compared with individual and aggregate data from an HBM study. In addition, the PBPK model was modified by adjusting input parameters and introducing new terms into the equations within the original model code. These modifications aimed to optimize the results compared to the original model, with some versions incorporating adjustments to account for the influence of menstruation in women. All models were evaluated to understand their strengths and weaknesses, providing guidance on the appropriate model to use according to specific scenarios. Results: The results obtained from the tested models were quite similar, with significant improvements observed only in the modified models. Simpler models also provided satisfactory results in scenarios involving low PFOS serum concentrations and recent exposure cessation. In many cases, predictions demonstrated high accuracy, particularly at the aggregate level and for women. Conclusions: These findings suggest that environmental protection agencies and health authorities may benefit from employing the tested models at the aggregate level as an initial step in HBM studies, rather than conducting more invasive and expensive screening campaigns.

Correlation between the presence of degenerated inclusion-bearing cells in voided urine samples and the occurrence of polyomavirus infection.

OBJECTIVE: The purpose of the present, prospective, cohort study was to monitor urine cytology samples from recipients of renal transplants to search for the occurrence of decoy cells and degenerated inclusion-bearing cells with an aim to correlate the existence of these cells with molecular detection of polyomavirus BK (BKV) DNA in urine. MATERIAL AND METHODS: This study included patients who underwent renal transplantation. Patients had their urine tested quarterly, during the first year post-transplantation, for the presence of decoy cells and degenerated cells, as well as by quantitative determination of BKV load in the urine and plasma. RESULTS: Three hundred and sixty-one examinations were performed on 101 patients within 12 months of attendance. Urine cytology results were: 198 (54.9%) negative and 60 (16.6%) positive for the presence of viral cytopathic effects depending on the presence of BKV infection, 72 (19.9%) positive for the manifestation of degenerated cells and 31 (8.6%) unsatisfactory for analysis. There was a subtle tendency towards the presence of degenerated inclusion-bearing cells in cases in which the virus was detected in voided urine. However, the presence of degenerated cells exhibited a tendency to BKV positivity in months 3, 6 and 9 and, exclusively in month 12, this trend was statistically significant. CONCLUSIONS: There were not enough strong morphological and staining elements to state the origin of the degenerated cells or to describe the nature of the infection (viral or bacterial), given that these cells were undergoing an apoptotic process in post renal transplant patients.

Combining land use regression models and fixed site monitoring to reconstruct spatiotemporal variability of NO2 concentrations over a wide geographical area.

The epidemiological research benefits from an accurate characterization of both spatial and temporal variability of exposure to air pollution. This work aims at proposing a method to combine the high spatial resolution of Land Use Regression (LUR) models with the high temporal resolution of fixed site monitoring data, to model spatiotemporal variability of NO2 over a wide geographical area in Northern Italy. We developed seasonal LUR models to reconstruct the spatial distribution of a scaling factor that relates local concentrations to those measured at two reference central sites, one for the northern flat area and one for the southern mountain area. We calculated the daily average concentrations at 19 locations spread over the study areas as the product of the local scaling factor and the reference central site concentrations. We evaluated model performance comparing modeled and measured NO2 data. LUR model's R2 ranges from 0.76 to 0.92. The main predictors refers substantially to traffic, industrial land use, buildings volume and altitude a.s.l. The model's performance in reproducing measured concentrations was satisfactory. The temporal variability of concentrations was well captured: Spearman correlation between model and measures was >0.7 for almost all sites. Model's average absolute errors were in the order of 10µgm-3. The model for the southern area tends to overestimate measured concentrations. Our modeling framework was able to reproduce spatiotemporal differences in NO2 concentrations. This kind of model is less data-intensive than usual regional atmospheric models and it may be very helpful to assess population exposure within studies in which individual relevant exposure occurs along periods of days or months.

Particulate matter air pollution components and risk for lung cancer.

BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. RESULTS: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.

Exposure to emissions from municipal solid waste incinerators and miscarriages: a multisite study of the MONITER Project.

BACKGROUND: Miscarriages are an important indicator of reproductive health but only few studies have analyzed their association with exposure to emissions from municipal solid waste incinerators. This study analyzed the occurrence of miscarriages in women aged 15-49years residing near seven incinerators of the Emilia-Romagna Region (Northern Italy) in the period 2002-2006. METHODS: We considered all pregnancies occurring in women residing during the first trimester of pregnancy within a 4km radius of each incinerator. Addresses were geocoded and exposures were characterized by a dispersion model (ADMS Urban model) producing pollution maps for incinerators based on PM10 stack measurements and for other pollution sources based on NOx ground measurements. Information on pregnancies and their outcomes was obtained from the Hospital Discharge Database. Simplified True Abortion Risks (STAR)×100 estimated pregnancies were calculated. We ran logistic regressions adjusting for maternal characteristics, exposure to other sources of pollution, and sites, considering the whole population and stratifying by miscarriage history. RESULTS: The study analyzed 11,875 pregnancies with 1375 miscarriages. After adjusting for confounders, an increase of PM10 due to incinerator emissions was associated with an increased risk of miscarriage (test for trend, p=0.042). The odds ratio for the highest quartile of exposed versus not exposed women was 1.29, 95% CI 0.97-1.72. The effect was present only for women without previous miscarriages (highest quartile of exposed versus not exposed women 1.44, 95% CI 1.06-1.96; test for trend, p=0.009). CONCLUSION: Exposure to incinerator emissions is associated with an increased risk of miscarriage. This result should be interpreted with those of a previous study on reproductive health conducted in the same area that observed an association between incinerator exposure and preterm births.

A comparison between self-reported and GIS-based proxies of residential exposure to environmental pollution in a case-control study on lung cancer.

In epidemiological studies both questionnaire results and GIS modeling have been used to assess exposure to environmental risk factors. Nevertheless, few studies have used both these techniques to evaluate the degree of agreement between different exposure assessment methodologies. As part of a case-control study on lung cancer, we present a comparison between self-reported and GIS-derived proxies of residential exposure to environmental pollution. 649 subjects were asked to fill out a questionnaire and give information about residential history and perceived exposure. Using GIS, for each residence we evaluated land use patterns, proximity to major roads and exposure to industrial pollution. We then compared the GIS exposure-index values among groups created on the basis of questionnaire responses. Our results showed a relatively high agreement between the two methods. Although none of these methods is the "exposure gold standard", understanding similarities, weaknesses and strengths of each method is essential to strengthen epidemiological evidence.

Posture and movement in healthy preterm infants in supine position in and outside the nest.

OBJECTIVE: To evaluate whether lying in a nest affects the posture and spontaneous movements of healthy preterm infants. METHOD: 10 healthy preterm infants underwent serial video recording in the supine position, when lying in a nest and outside it, at three ages: 30-33 weeks postmenstrual age (PMA) (early preterm), 34-36 weeks PMA (late preterm) and 37-40 weeks PMA (term). The nest was shell-shaped, made by putting two rolled blankets in a form of an oval. Posture was assessed both before and after general movements by scoring the predominant postural pattern. Movements towards and across the midline, elegant wrist movements, abrupt hand and/or limb movements, rolling to side, and frozen postures of the arms and legs were assessed during four general movements. All data relating to motor and postural items were normalised into frequencies of events per minute because the general movements varied in duration. RESULTS: When lying in the nest, the infants more often displayed a flexed posture with shoulder adduction and elbow, and hip and knee flexion, and the head was frequently in the midline. The nest was also associated with an increase in elegant wrist movements and movements towards and across the midline and a reduction in abrupt movements and frozen postures of the limbs. The nest did not affect the occurrence of asymmetrical tonic neck posture. CONCLUSIONS: A nest promotes a flexed posture of the limbs with adduction of shoulders, facilitates elegant wrist movements and movements towards and across the midline and reduces abrupt movements and frozen postures of the arms and legs.

Alternaria spores at different heights from the ground.

BACKGROUND: Alternaria tenuis (Alt) is one of the main allergens in pediatric age. In temperate climates, airborne Alt spores are detectable from May to November with peaks in late summer and autumn. Sensitized children display symptoms even in the absence of airborne Alt spores. Alt spore concentration, as well as pollen, is usually detected by fixed devices located on the roof of a building at a height of 10-20 m. The aim of the current study is to find out whether ground-level (50 cm) Alt spore concentrations are different from those at roof-top level, even during low-concentration periods. METHODS: Alt samples were taken simultaneously using a Hirst fixed volumetric collector (FVC) placed on a 15 m-high roof and by a portable volumetric collector (PVC). Firstly, the results of FVC and PVC, both placed on the roof-top, were compared to verify the correlation coefficient of the two samplers. Subsequently, the PVC was placed 50 cm above the ground in a courtyard (30 samplings) and in private green areas (50 samplings). The results were compared by statistical analysis (Student's t-test or K-S test). RESULTS: The values of the 20 samples taken jointly in summer time (FVC 195 +/- 134 spores/m(3); PVC = 134 +/- 131 spores/m(3)) showed a good correlation between the two samplers (r = 0.850; P < 0.01), with a correction factor equal to 1.177. 1. Thirty samples obtained in summer and winter when the PVC was positioned in an enclosed courtyard directly below the FVC showed no significant difference (PVC, 181 +/- 194 spores/m(3); FVC, 152 +/- 145 spores/m(3); P = 0.221). 2. Fifty samples taken by PVC placed in private green areas in a low-concentration period, showed significantly higher concentrations than by FVC: PVC, 531 +/- 925 spores/m(3); FVC, 25 +/- 51 spores/m(3) (K-S test: P < 0.0001). In particular, 33 samples taken in winter when Alt counts by FVC were <10 spores/m(3) still demonstrated highly significant differences: PVC, 398 +/- 961 spores/m(3); FVC, 2.0 +/- 2 spores/m(3) (K-S test: P < 0.0001). CONCLUSION: Our results lead to the conclusion that Alt spore concentration is significantly higher at ground level in the presence of vegetation, even when the spore concentration is very low (<10 spores/m(3)). These results further suggest that the individual's exposure to Alt, especially in the case of children, is underestimated by samples taken at roof-top level by FVC.

Early intracardiac thrombosis in preterm infants and thrombolysis with recombinant tissue type plasminogen activator.

OBJECTIVES: To determine the incidence of catheter related thrombosis and to test the efficacy of recombinant tissue type plasminogen activator (rt-PA) in preterm infants. STUDY DESIGN: From January 1995 to December 1998, echocardiography was performed in the first few days of life in 76 very low birthweight (< or = 1500 g) infants out of a total of 147 having an umbilical catheter placed. When intracardiac thrombosis was diagnosed, rt-PA infusion was performed. RESULTS: Four infants (5%) developed an intracardiac thrombosis during the first few days of life. In three of them, rt-PA at a dose of 0.4-0.5 mg/kg in a 20-30 minute bolus led to dissolution of the clot. One patient received a three hour infusion after the bolus, at a dose of 0.1 mg/kg/h, with resolution of the thrombus. No systemic effects were observed after rt-PA infusion. CONCLUSIONS: Early thrombosis may occur as a complication of umbilical catheterisation in preterm infants; early echocardiographic detection of this disorder allows complete, safe, and rapid lysis with rt-PA.

[Case-control study in an area of the province of Ferrara having a high mortality rate for lung tumors]. / Studio caso-controllo in un'area della provincia di Ferrara a elevata mortalità per tumore del polmone.

The province of Ferrara represents one of the areas with the highest mortality rate for lung cancer in Italy. The aim of the study is to evaluate the relative importance of the main known risk factors for lung cancer in that area. It is a case control study based on the population where the cases under study (249) are selected from subjects deceased over the period 1988-1993 in the territory of the ex USL 33 (Local Health Authority) of Comacchio, while the controls (500) lived in the same area. The statistical analysis showed the same information that can be found in other medical literature regarding the known risk factors: smoking (OR = 3.7-44.9 per n. cigarettes/die), spouse passive smoking (OR = 1.1), passive smoking due to social setting (pubs) (OR = 1.9), vegetable diet (OR = 0.4). A important role was played by the factors linked to socio-economic differences. There was a significant increase in risk for those who had lived in "casazze" in the area, which are typical homes of the poorer social classes. There was also a significant increase in risk for subjects with a lower level of education. To obtain these results the analysis method known as "classification trees" was also used in order to verify its possible use in the public health sector.

Absence of the association with CC chemokine receptor 5 polymorphism in polymyalgia rheumatica.

OBJECTIVE: Elevated RANTES serum levels are present in polymyalgia rheumatica (PMR) patients with active disease. Chemokines may contribute to the inflammatory PMR process through their binding to CC chemokine receptor 5 (CCR5). The aim of this study was to examine if the 32 base pair deletion allele in CCR5 (CCR5 delta 32 allele) might be associated with PMR susceptibility and influence the disease outcome. METHODS: We enrolled 88 consecutive patients with PMR residing in the Reggio Emilia area (Italy) who had a follow-up duration of at least one year. As a control group we used 86 healthy blood donors from the same geographic area. The CCR5 genotype of all PMR patients and controls was studied by polymerase chain reaction amplification of the region which includes the 32 deletion (CCR5 delta 32). RANTES serum levels were measured by commercial ELISA kits in CCR5 delta 32 heterozygous and CCR5 homozygous PMR patients at diagnosis before starting corticosteroid therapy and again after 6 months of therapy, as well as in 28 healthy subjects over 50 years of age. RESULTS: Frequencies of the CCR5 and CCR5 delta 32 alleles in patients and controls did not differ significantly. Homozygosity for CCR5 delta 32 was not detected in PMR patients and was detected in only one of the controls. No significant differences were observed between the patients carrying the CCR5 delta 32 allele and those homozygous for the normal CCR5 allele when we compared sex, presence of distal synovitis and systemic signs and/or symptoms, initial and cumulative prednisone dose, duration of therapy, ESR at diagnosis, frequency of relapse/recurrence and RANTES serum levels at diagnosis and after 6 months of corticosteroids. CONCLUSION: These results indicate that the frequency of the 32 deletion of the CCR5 receptor was not significantly different between PMR patients and healthy controls, and this genotype does not appear to be associated with the susceptibility to or severity of PMR.

[The elderly and street safety: analysis of geographical differences in the province of Modena]. / Gli anziani e la sicurezza stradale: analisi delle differenze territoriali nella provincia di Modena.

The progressive ageing of the population and the increasing importance of road traffic in our society renders the relationships between elderly people and road traffic an increasingly important problem. In the province of Modena elderly people are not equally distributed over the area, in fact they are concentrated mainly in small towns situated in hill/mountain areas. This study aims to verify the risk conditions for elderly people in relation to road accidents in different areas in the province of Modena. The time-series analyses of road accidents involving elderly people, from 1991 to 1996, in the province of Modena were carried out on 2,291 cases out of 16,267 total accidents. The results of the analysis showed statistically significant differences for the ratio of fatalities according to the geographical area, divided into low plain, urban and hill/mountain areas (p = 0.015 urban and hill/mountain areas). No statistically significant differences were obtained for the division into small, medium and big towns, however such analysis indicated an increased risk for elderly people living in small towns, regardless of the means of transport involved in the accident (p = 0.052). The relationship between old people and road traffic seems to be worse in the small towns situated in hill/mountain areas, where there is a higher number of elderly people, and where the facilities probably have not adapted themselves to the social-cultural changes that take place.

Audiovisual sexual stimulation by virtual glasses is effective in inducing complete cavernosal smooth muscle relaxation: a pharmacocavernosometric study.

Audiovisual sexual stimulation (AVSS) is frequently employed to promote cavernosal smooth muscle relaxation (SMR) in hemodynamic diagnostic settings for erectile dysfunction. Our aim has been to adapt conventional AVSS to the particular test conditions of pharmacocavernosometry and pharmacocavernosography (DICC), by the use of virtual glasses. Thirty-seven consecutive patients undergoing DICC were randomized in two groups: no-AVSS and AVSS through commercially available virtual glasses (VG-AVSS) with tri-dimensional capabilities and stereophonic headphones. Such device partially excludes the patient from the surrounding environment. In both groups a standard dose of vasoactive agents was intracavernosally administered, and possibly repeated (re-dosing), until complete SMR was obtained (3 doses/patient maximum). Psychometric tests (State Trait Anxiety Inventory and ad hoc visual analogue scales for embarrassment, stress and pain) were administered before and after DICC. The no-AVSS group consisted of 18 patients, the AVSS group of 19. Number of needed vasoactive agent doses: in the no-AVSS group 6 patients needed 1 dose, 3 patients 2, 9 patients 3 (mean dose number: 2.17); in the AVSS group 15 patients needed 1 dose, 1 patient 2, 3 patients 3 (mean dose number: 1.37). The difference in the number of doses used in the two groups was statistically significant (Student's t-test P = 0.007). Complete SMR, regardless of the number of used doses: in the no-AVSS group 9 patients (50%) achieved complete SMR, in the AVSS group 16 patients (84.2%). The difference in the two groups was statistically significant (chi-square P = 0.026). From evaluated psychometric measures no statistically significant difference between the two groups was detected. VG-AVSS significantly promotes complete SMR without increasing test related stress or anxiety. Its induced arousal suggests the possibility of performing dynamic evaluations of the erectile function with the oral agent sildenafil in place of intracavernosally administered vasoactive agents. VG-AVSS furthermore constitutes a promising tool for the investigation of normal physiology and pathophysiology of female sexual function.

Erythrocyte sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in polymyalgia rheumatica: a prospective follow-up study.

OBJECTIVE: To determine the frequency and clinical features of patients with polymyalgia rheumatica (PMR) and normal erythrocyte sedimentation rate (ESR) at diagnosis or during relapse/recurrence. To evaluate the usefulness of C-reactive protein (CRP) and ESR in the assessment of PMR activity. METHODS: A prospective follow-up study on 177 consecutive patients meeting the criteria for PMR diagnosed over a 5-year period was conducted in two Italian secondary referral centers of rheumatology. At diagnosis and during follow-up, ESR (Westergren method) and CRP (nephelometry) were measured in all patients. Phenotypic analysis of lymphocyte subpopulations was performed on 78 PMR patients at diagnosis. A two-color technique using the association of specific monoclonal antibodies was applied. A control group consisting of 18 healthy adults older than 60 years was matched for age and sex with the PMR patients. RESULTS: Ten of 177 (6%) patients had normal ESR values at diagnosis (< or = 30 mm/h). Patients with normal ESR were predominantly men and had lower CRP levels; systemic signs and symptoms were more frequent in patients with higher ESR. The percentages of circulating CD8+ cells were similar in the two groups. CRP values at diagnosis were normal in only 2 of 177 (1%) patients. CRP values were elevated in 9 of 10 patients with normal ESR at diagnosis. Twenty-five episodes of relapse/recurrence with normal ESR occurred in 17 patients. CRP was high in 62% of these episodes. Results of univariate analysis indicated that the 10th percentile for ESR (40 mm/h) and the 70th percentile for CRP (7.8 mg/dL) values at diagnosis were the best cutoff points that discriminate between patients with and without relapse/recurrence. Cox proportional hazards modeling showed that ESR greater than 40 mm/h and CRP greater than 7.8 mg/dL at diagnosis were the two variables that independently increased the risk of relapse/recurrence. However, the relative risk related to ESR was twice than that related to CRP (4.9 vs 2.1). CONCLUSION: PMR with a normal ESR at diagnosis was infrequent in our study compared with previous studies. ESR was a superior predictor of relapse than CRP. However, CRP was a more sensitive indicator of current disease activity.

Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: association with disease risk and severity.

OBJECTIVE: Intercellular adhesion molecule 1 (ICAM-1) is widely distributed in shoulder synovial membrane of active polymyalgia rheumatica (PMR) and strongly expressed in granulomatous inflammatory infiltrate of the temporal artery in giant cell arteritis (GCA). ICAM-1 genes may contribute to the inflammatory PMR/GCA processes. We examined potential associations of ICAM-1 gene polymorphisms with PMR/GCA susceptibility and severity. METHODS: We enrolled 121 consecutive patients with "pure" PMR and 56 patients with biopsy positive GCA residing in Reggio Emilia, Italy. Among patients with PMR, 91 had a followup duration of at least one year. Selected as control subjects were 228 healthy blood donors, 75 patients with nonarteritic central retinal artery occlusion, and 116 cataract surgery patients from the same geographic area. All PMR/GCA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphism at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: The frequency of R241 was significantly higher in PMR/GCA patients [p = 0.00001, odds ratio (OR) 5.0 (95% confidence intervals, CI 2.6-9.6) ], in pure PMR patients [p = 0.00001, OR 5.0 (95% CI 2.5-10.0)], and in GCA patients [p = 0.00005; OR 5.0 (95% CI 2.2-11.5)] compared to the healthy controls. The frequency of R241 was significantly higher in total PMR/GCA patients compared to patients with nonarteritic central retinal artery occlusion [p = 0.0007; OR 5.3 (95% CI 1.8-15.5)] and cataract surgery patients [p = 0.0003; OR 4.1 (95% CI 1.8-9.0)]. The distribution of E/K 469 genotype was similar in PMR/GCA patients and in the 3 control groups. Cox proportional hazards modeling identified 2 variables that independently increased the risk of PMR relapse/recurrence: erythrocyte sedimentation rate at diagnosis > 72 mm/h [relative risk 1.6 (95% CI 1.1-2.3)] and the presence of R241 allele [relative risk 1.6 (95% CI 1.1-2.4)]. CONCLUSION: Our findings show that G/R 241 polymorphism of ICAM-1 is associated with PMR/GCA susceptibility and confers an increased risk of relapse/recurrence in PMR.

HLA-DRB1, DQA1, and DQB1 alleles associated with giant cell arteritis in northern Italy.

OBJECTIVE: To evaluate by molecular typing the possible associations of HLA-DRB1, DQA1, and DQB1 alleles with biopsy proven giant cell arteritis (GCA) in a Mediterranean country, and to examine possible relationships between these alleles and GCA clinical subsets. METHODS: Thirty-nine patients from the Reggio Emilia area diagnosed over a 12 year period with biopsy proven GCA were studied. The clinical findings at diagnosis and during the followup were evaluated through interviews and by reviewing the medical records. HLA-DRB1, DQA1, and DQB1 alleles were determined in the 39 patients and in 250 healthy controls from the same geographic area by polymerase chain reaction amplification using sequence-specific primers. RESULTS: No associations were found between GCA and the shared epitope, the DRYF epitope, or the DRB1*04 or DQA1 alleles. The only significant association was with DQB1*0302 allele (p = 0.03, RR = 2.2). However, the association was weak and the significance was lost when corrected for the number of antigens tested. The frequencies of DQB1*0301 and 0302 in DR4 patients were not significantly different from those observed in DR4 positive controls. Significant associations were found between DRB1*04 allele and the presence of systemic signs and/or symptoms (p = 0.04, RR = 1.5) and between DRB1*07 allele and the male patients (p = 0.04, RR = 2.6). CONCLUSION: Our data showed no associations of biopsy proven GCA with HLA-DRB1*04 and HLA-DRB1*01 alleles, rheumatoid epitope, or DRYF epitope. Discrepancies with other studies may be related to the different ethnic backgrounds of the populations studied and to differences in the referral patterns of patients with GCA.

First-trimester fetal sex prediction by deoxyribonucleic acid analysis of maternal peripheral blood.

OBJECTIVES: We investigated whether the number of weeks of gestation influences the accuracy of first-trimester fetal sex prediction by analysis of deoxyribonucleic acid extracted from whole maternal blood. A comparison was also made to determine whether a difference exists between this approach and the deoxyribonucleic acid analysis of transcervical cells performed on the same group of subjects. STUDY DESIGN: Deoxyribonucleic acid was isolated from 50 maternal blood samples taken between gestational weeks 7 and 11. The sex of the fetus was assessed by nested polymerase chain reaction specific for the amelogenin gene. A receiver-operating characteristic curve analysis was used to correlate the accuracy of fetal gender prediction with the gestational age and also to compare the goodness of the 2 methods under investigation. RESULTS: Analysis of the receiver-operating characteristic curve provided a cutoff value of 9 weeks 4 days of gestation for both tests, indicating that a higher degree of accuracy in the sex assignment was obtained in those samples taken before or at this time. However, this difference was statistically significant only for analysis of deoxyribonucleic acid from maternal blood. The comparison between tests of deoxyribonucleic acid from maternal blood and from transcervical cells showed that the first approach is better, although a statistically significant difference was not found. CONCLUSION: Analysis of maternal blood deoxyribonucleic acid is a better approach than analysis of trans-cervical cell deoxyribonucleic acid in fetal sex prediction. The highest degree of accuracy is obtained when blood is drawn before 10 weeks of gestation. This can be important when sampling of chorionic villi should be avoided because of the risk of an X-linked disease when the fetal sex is female.

Prediction of successful outcome in a randomised controlled trial of the long-term efficacy of interferon alpha treatment for chronic hepatitis C.

To evaluate the efficacy of a 12-month course of recombinant interferon alpha (IFN-alpha2b), and to assess predictive factors of successful response to IFN therapy in chronic active hepatitis C (HCV CAH), 242 patients with histologically proven HCV CAH were assigned randomly to two groups, one treated with IFN-alpha2b (3 MU three times weekly, intramuscularly), the other untreated. To determine the efficacy of IFN-alpha2b 12 months after therapy, a second liver biopsy was carried out on 100 treated patients and 27 untreated patients. The biochemical, virological, and serological response of patients followed up for at least 50 months after treatment was also evaluated to confirm the efficacy of IFN-alpha2b. The genotypes of infecting HCV, anti-HCV core IgM, and HCV-RNA concentrations were also analysed and the predictors of response determined by univariate and multivariate analyses. Response was defined in terms of the normalisation of aminotransferase activities and the disappearance of HCV-RNA. The overall long-term response was 39.4%. Anti-HCV core IgM levels were significantly lower in long-term responders. Patients with increased levels of IgM anti HCV core (>3.8 sample/cut-off), infected with genotype 1b were nonresponders. Liver histology improved significantly in patients with long-term response. Multivariate analysis identified three independent predictors of the likelihood of long-term response to IFN therapy: age younger than 40 years, basal anti-HCV core IgM levels < or = 3.8, and genotypes other than 1b. These data indicate that the treatment with IFN-alpha2b used in this randomised controlled trial is effective in HCV CAH. Anti-HCV core IgM was the strongest predictor of long-term response in the present study.

HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation with disease severity.

OBJECTIVE: To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity. METHODS: A five year prospective follow up study of 92 consecutive PMR patients diagnosed by the secondary referral centre of rheumatology of Reggio Emilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patients, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 controls from the same geographical area by polymerase chain reaction amplification and oligonucleotide hybridisation. RESULTS: No significant differences were observed in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70-74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis indicated that an erythrocyte sedimentation rate (ESR) at diagnosis > 72 mm 1st h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rheumatoid epitope were significant risk factors associated with relapse/recurrence. Cox proportional hazards modelling identified two variables that independently increased the risk of relapse/recurrence: ESR at diagnosis > 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epitope (RR=2.7). CONCLUSION: These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at diagnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity.