Mechanical behavior of a Y-TZP ceramic for monolithic restorations: effect of grinding and low-temperature aging.

This study aimed to investigate the effects of grinding with diamond burs and low-temperature aging on the mechanical behavior (biaxial flexural strength and structural reliability), surface topography, and phase transformation of a Y-TZP ceramic for monolithic dental restorations. Disc-shaped specimens (Zirlux FC, Ivoclar Vivadent) were manufactured according to ISO 6872 (2008) and divided in accordance with two factors: "grinding - 3 levels" and "LTD - 2 levels". Grinding was performed using a contra-angle handpiece under constant water-cooling with different grit-sizes (extra-fine and coarse diamond burs). LTD was simulated in an autoclave at 134°C, under a pressure of 2 bar, over a period of 20h. Surface topography analysis showed an increase in roughness based on surface treatment grit-size (Coarse>Xfine>Ctrl), LTD did not influence roughness values. Both grinding and LTD promoted an increase in the amount of m-phase, although different susceptibilities to degradation were observed. According to existing literature the increase of m-phase content is a direct indicative of Y-TZP degradation. Weibull analysis showed an increase in characteristic strength after grinding (Coarse=Xfine>Ctrl), while for LTD, distinct effects were observed (Ctrl

Fatigue limit of polycrystalline zirconium oxide ceramics: Effect of grinding and low-temperature aging.

The following study aimed to evaluate the effect of grinding and low-temperature aging on the fatigue limit of Y-TZP ceramics for frameworks and monolithic restorations. Disc specimens from each ceramic material, Lava Frame (3M ESPE) and Zirlux FC (Ivoclar Vivadent) were manufactured according to ISO:6872-2008 and assigned in accordance with two factors: (1) "surface treatment"-without treatment (as-sintered, Ctrl), grinding with coarse diamond bur (181µm; Grinding); and (2) "low-temperature aging (LTD)" - presence and absence. Grinding was performed using a contra-angle handpiece under constant water-cooling. LTD was simulated in an autoclave at 134°C under 2-bar pressure for 20h. Mean flexural fatigue limits (20,000 cycles) were determined under sinusoidal loading using stair case approach. For Lava ceramic, it was observed a statistical increase after grinding procedure and different behavior after LTD stimuli (Ctrl

Low-temperature degradation of Y-TZP ceramics: A systematic review and meta-analysis.

The aim of this study was to systematically review the literature to assess if low-temperature degradation (LTD) simulation in autoclave promotes deleterious impact on the mechanical properties and superficial characteristics of Y-TZP ceramics compared to the non-aged protocol. The MEDLINE via PubMed electronic database was searched with included peer-reviewed publications in English language and with no publication year limit. From 413 potentially eligible studies, 49 were selected for full-text analysis, 19 were included in the systematic review with 12 considered in the meta-analysis. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. Statistical analysis was performed using RevMan 5.1, with random effects model, at a significance level of p<0.05. Descriptive analysis of monoclinic phase content data showed that aging in autoclave promotes an increase in m-phase content (ranging from 0% up to 13.4% before and 2.13% up to 81.4% after aging) with intensity associated to the material susceptibility and to the aging parameters (time, pressure and temperature). Risk of bias analysis showed that only 1 study presented high risk, while the majority showed medium risk. Five meta-analyzes (factor: aging×control) were performed considering global and subgroups analyzes (pressure, time, temperature and m-phase % content) for flexural strength data. In the global analysis a significant difference (p<0.05) was observed between conditions, favoring non-aging group. Subgroup analysis revealed statistical difference (p<0.05) favoring non-aging, for aging time >20h. However, for shorter aging times (≤20h), there was no difference between groups. Pressure subgroup analysis presented a statistical difference (p<0.05) only when a pressure ≥2bar was employed, favoring non-aging group. Temperature subgroup analysis showed a statistical difference (p<0.05) only when temperature=134°C was used, favoring the non-aging group. M-phase % content analysis presented statistical difference (p<0.05) when more than 50% of m-phase content was observed, favoring non-aging group. High heterogeneity was found in some comparisons. Aging in autoclave promoted low-temperature degradation, impacting deleteriously on mechanical properties of Y-TZP ceramics. However, the effect of LTD depends on some methodological parameters indicating that aging time higher than 20h; pressure ≥2bar and temperature of 134°C are ideal parameters to promote LTD effects, and that those effect are only observed when more than 50% m-phase content is observed.

Association between hepatitis B or hepatitis C virus infection and risk of pancreatic adenocarcinoma development: a systematic review and meta-analysis.

BACKGROUND: Pancreatic adenocarcinoma (PAC) is an aggressive cancer with a poor prognosis. To date, PAC causes are still largely unknown. Antigens and replicative sequences of oncogenic hepatitis B (HBV) and hepatitis C (HCV) virus were detected in different extra-hepatic tissues, including pancreas. OBJECTIVE: a systematic review and meta-analysis of epidemiological studies assessing PAC risk in patients with HBV/HCV chronic infections. METHODS: In September 2012, we extracted the articles published in Medline, Embase and the Cochrane Library, using the following search terms: "chronic HBV" and "HCV", "hepatitis", "PAC", "risk factors", "epidemiology". Only case/control (C/C), prospective/retrospective cohort studies (PCS/RCS) written in English were collected. RESULTS: four hospital-based C/C studies and one PCS, in HBV-infected patients and two hospital-based C/C studies and one RCS in HCV-infected subjects met inclusion criteria. In these studies HBsAg positivity enhanced significantly PAC risk (RR = 1.18, 95% CI:1.04-1.33), whereas HBeAg positivity (RR = 1.31, 95% CI:0.85-2.02) as well as HBsAg negative/HBcAb positive/HBsAb positive pattern (RR = 1.12, 95% CI:0.78-1.59) and HBsAg negative/HBcAb positive/HBsAb negative pattern (RR = 1.30, 95% CI:0.93-1.84) did not. Relationship between PAC risk and anti-HCV positivity was not significant, although it reached a borderline value (RR = 1.160, 95% CI:0.99-1.3). CONCLUSIONS: HBV/HCV infection may represent a risk factor for PAC, but the small number of available researches, involving mainly populations of Asian ethnicity and the substantial variation between different geographical areas in seroprevalence of HBV/HCV-antigens/antibodies and genotypes are limiting factors to present meta-analysis.

Hepatitis B and C virus infections as possible risk factor for pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAC) is a very aggressive and lethal cancer, with a very poor prognosis, because of absence of early symptoms, advanced stage at presentation, early metastatic dissemination and lack of both specific tests to detect its growth in the initial phases and effective systemic therapies. To date, the causes of PAC still remain largely unknown, but multiple lines of evidence from epidemiological and laboratory researches suggest that about 15-20% of all cancers are linked in some way to chronic infection, in particular it has been shown that several viruses have a role in human carcinogenesis. The purpose of this report is to discuss the hypothesis that two well-known oncogenic viruses, Human B hepatitis (HBV) and Human C hepatitis (HCV) are a possible risk factor for this cancer. Therefore, with the aim to examine the potential link between these viruses and PAC, we performed a selection of observational studies evaluating this association and we hypothesized that some pathogenetic mechanisms involved in liver carcinogenesis might be in common with pancreatic cancer development in patients with serum markers of present or past HBV and HCV infections. To date the available observational studies performed are few, heterogeneous in design as well as in end-points and with not univocal results, nevertheless they might represent the starting-point for future larger and better designed clinical trials to define this hypothesized relationship. Should these further studies confirm an association between HBV/HCV infection and PAC, screening programs might be justified in patients with active or previous hepatitis B and C viral infection.

Interleukin-4/interleukin-4 receptor gene polymorphisms in hand osteoarthritis.

OBJECTIVE: IL-13/IL-4/IL-4R system has strong chondroprotective activity. We investigated polymorphisms in these genes as potential hand osteoarthritis (OA) susceptibility loci by performing a case-control association study. METHODS: Eighteen common single nucleotide polymorphisms (SNPs) (nine in IL-4R, five in IL-4 and four in IL-13) were genotyped in 403 patients (380 females) with hand OA and 322 healthy controls (308 females). RESULTS: Two SNPs (rs1805013 and rs1805015), mapping to the IL-4R gene, were associated with P-values of 0.0116 and 0.0305 respectively in the whole sample. As far as the non-erosive hand OA group (n=159) is concerned, the significance level of association of SNP rs1805013 is increased. After correction for multiple testing (correction for the 54 tests) the significance was not retained. None of the IL-13 SNPs analyzed showed association with hand OA. Some of the analyzed SNP within the IL-4 gene showed significant association with hand OA only when considering subgroups of patients. With respect to the CMC1 OA group, two SNPs in IL-4 (rs2243250 and rs2243274) showed association with a P-value of 0.027 and 0.018 respectively. None of these associations remained after correction for multiple testing. CONCLUSIONS: The present study shows a trend to an association between non-erosive hand OA in Caucasian population and a genetic variant in the coding region of IL-4R gene. Our results, in keeping with previous data on hip OA, confirm the suggestion that IL-4/IL-4R system plays a role in OA pathogenesis. Further confirmation studies on different populations are necessary.

Circulating RANKL/OPG in polymyalgia rheumatica.

OBJECTIVE: To evaluate whether RANKL/OPG balance is modified in PMR patients, either in the active phase of the disease or during corticosteroid treatment. METHODS: Circulating levels of RANKL and OPG were assayed by enzyme-linked immunosorbent assay in PMR patients with active untreated disease and in patients treated by corticosteroids over a 12-month follow-up period. RESULTS: We found no statistically significant differences in circulating levels of OPG between PMR patients either in the active phase of the disease or during all follow-up period compared to normal controls. On the other hand, systemic production of sRANKL is increased and is not modulated by corticosteroid treatment. CONCLUSION: In PMR increased levels of sRANKL may be related to bone osteoporosis. Further investigations are necessary to evaluate the relationship between the RANK/RANKL/OPG system and bone turnover in PMR patients.

Synovial expression of vasoactive intestinal peptide in polymyalgia rheumatica.

OBJECTIVE: Polymyalgia rheumatica (PMR) is an inflammatory disease that typically affects elderly people. Its clinical hallmark is the severity of pain in the shoulder and pelvic girdle. Mild to moderate synovitis and/or bursitis of the joints involved has been described. Neuropeptides are involved in nociception and modulation of inflammatory reaction. To evaluate whether neuropeptides have a role in PMR pathophysiology, we studied the expression of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) in shoulder synovial tissues of PMR patients. METHODS: Synovial expression of neuropeptides was investigated by immunohistochemical analysis, in two groups of PMR patients: the first one at the onset of disease and the second one after corticosteroid treatment, and in other joint diseases, rheumatoid arthritis (RA) and osteoarthritis (OA). RESULTS: The only significant expression of VIP was found in PMR and, to a lesser extent, in RA synovial tissue. In PMR, we observed VIP immunostaining both in the lining layer and in the sublining area. In patients on corticosteroid treatment VIP lining layer expression was not significantly different while VIP positive cells in the sublining area were almost absent. CONCLUSION: Local VIP production in PMR synovial tissue might contribute to the typical musculoskeletal discomfort and it may have a role in the immunomodulation of synovial inflammation.

Elevated serum levels of soluble interleukin-4 receptor in osteoarthritis.

OBJECTIVE: To test the importance of the interleukin-4 (IL-4)/IL-4 receptor (IL-4R) system in osteoarthritis (OA) we evaluated soluble IL-4R (sIL-4R) levels in sera of patients with different forms of OA and healthy individuals. METHODS: We recruited: 141 patients with hand OA, 70 with nodal and 71 with erosive hand OA; 64 patients undergoing total joint replacement, 34 with hip and 30 with knee OA; and 38 ethnically and geographically age-matched healthy individuals [normal controls (NC)]. RESULTS: Serum sIL-4R concentration was found to be significantly higher in all OA patients than that in NC. When patients were divided into four subgroups (nodal, erosive, hip and knee OA) significant differences were present when comparing NC with each subgroup. This was true also when small-joint OA groups were compared with large-joint OA groups, the latter being associated with higher IL-4R levels. CONCLUSIONS: We found increased levels of sIL-4R in OA patients compared with healthy individuals. We speculate that this reduces availability of IL-4, and its effects on chondrocytes.

Vascular endothelial growth factor activities on osteoarthritic chondrocytes.

OBJECTIVE: Evaluation of the role of VEGF in cartilage pathophysiology. METHODS: VEGF release from chondrocytes in the presence of IL-1beta, TGFbeta and IL-10 was detected by immunoassay. VEGF receptor -1 and -2 expression and VEGF ability to modulate caspase -3 and cathepsin B expression were detected by immunohistochemistry on cartilage biopsies and cartilage explants. VEGF effects on chondrocyte proliferation was analysed by a fluorescent dye that binds nucleic acids. RESULTS: VEGF production by osteoartritis (OA) chondrocytes was significantly reduced by IL-1beta while it was increased in the presence of TGFbeta. Cartilage VEGFR-1 immunostaining was significantly downregulated in 'early' OA patients compared to normal controls (NC). VEGFR-2 expression was negligible both in OA and in NC. VEGF decreased the expression of caspase-3 and cathepsin B, whereas it did not affect proliferation. CONCLUSION: VEGF is able to down-modulate chondrocyte activities related to catabolic events involved in OA cartilage degradation.

[Multiple Spitz nevus]. / Nevo di Spitz multiplo.

Benign juvenile melanoma was originally described and differentiated from malignant melanoma by Sophie Spitz in 1948. The solitary form is the most frequent and usually appears on the face and extremities of young children and adolescents as a solitary, hairless, dome-shaped papule or nodule, varying in size from 3 to 15 mm. It can be of a wide spectrum of colors including pink, yellow, red, brown, purple and black, representing 1% to 8% of melanocytic tumors in children. Histologically, Spitz nevus has been subdivided into junctional, compound and intradermal type according to the location of neoplastic melanocytes in the skin. Rarely multiple benign juvenile melanoma arranged in clusters (agminated) or widespread (disseminated) are described. Less than 50 cases have been reported in the world literature. The grouped form usually occurs on the face of children on normal, but also hyperpigmented or hypopigmented skin, while the disseminated one in adults. A case of multiple agminated Spitz nevus arised on the face of a 2 years old girl is reported. The clinical presentations with a 3 years follow-up and the histologic features of this nevus are described as well as the therapeutic approach.

Down-modulation of chemokine receptor cartilage expression in inflammatory arthritis.

OBJECTIVE: To evaluate in vivo expression of chemokine receptors in cartilage tissue samples from healthy and diseased joints. METHODS: Presence and distribution of several chemokine receptors in cartilage samples from patients with osteoarthritis (OA) or inflammatory arthritis (IA) and from multi-organ donors were assessed by immunohistochemistry. The expression of messenger RNA (mRNA) for chemokine receptors was also analysed by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Normal and OA-affected cartilage showed a moderate to high expression of chemokine receptors, while staining of IA samples ranged from low to absent. Differences between OA and IA samples were present for all receptors but CCR2 and CXCR4. Moreover, mRNAs for CCR1, CCR5 and CXCR1 were found both in normal and pathological chondrocytes, suggesting that chemokine receptor down-modulation seen in IA samples could be a post-transcriptional event. CONCLUSION: Data on normal and pathological chondrocytes underline the role of chemokines in cartilage homeostasis and suggest an imbalance towards catabolic processes in inflammatory conditions.

Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis.

Osteoarthritis and rheumatoid arthritis are characterized by focal loss of cartilage due to an up-regulation of catabolic pathways, induced mainly by pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha). Since reactive oxygen species are also involved in this extracellular-matrix-degrading activity, we aimed to compare the chondrocyte oxidative status responsible for cartilage damage occurring in primarily degenerative (osteoarthritis) and inflammatory (rheumatoid arthritis) joint diseases. Human articular chondrocytes were isolated from patients with osteoarthritis or rheumatoid arthritis, or from multi-organ donors, and stimulated with IL-1beta and/or TNFalpha. We evaluated the oxidative stress related to reactive nitrogen and oxygen intermediates, measuring NO(-)(2) as a stable end-product of nitric oxide generation and superoxide dismutase as an antioxidant enzyme induced by radical oxygen species. We found that cells from patients with osteoarthritis produced higher levels of NO(-)(2) than those from patients with rheumatoid arthritis. In addition, IL-1beta was more potent than TNFalpha in inducing nitric oxide in both arthritides, and TNFalpha alone was almost ineffective in cells from rheumatoid arthritis patients. We also observed that the intracellular content of copper/zinc superoxide dismutase (Cu/ZnSOD) was always lower in rheumatoid arthritis chondrocytes than in those from multi-organ donors, whereas no differences were found in intracellular manganese SOD (MnSOD) or in supernatant Cu/ZnSOD and MnSOD levels. Moreover, intracellular MnSOD was up-regulated by cytokines in osteoarthritis chondrocytes. In conclusion, our results suggest that nitric oxide may play a major role in altering chondrocyte functions in osteoarthritis, whereas the harmful effects of radical oxygen species are more evident in chondrocytes from patients with rheumatoid arthritis, due to an oxidant/antioxidant imbalance.

IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: interaction with their plasma levels.

The balance between interleukin-1 (IL-1) and its competitive antagonist IL-1 receptor antagonist (IL-1Ra) may contribute to the pathogenesis of rheumatoid arthritis (RA). We analysed the frequency of different alleles in the IL-1B gene (at -511 and at +3954) as well as in the IL-1Ra gene (at +2018) in an association study involving 297 RA patients and 112 healthy controls from the same geographic area. We tested associations with RA susceptibility or severity, and with circulating levels of IL-1Ra and IL-1beta. Carriage of the rare IL-1B (+3954) allele 2 was increased in destructive arthritis (DRA) as compared to non-destructive arthritis (NDRA) (OR 1.7, 95% CI 1.1-2.8, 49.0% vs 35.9%) and controls (OR 1.7, 95% CI 1.1-2.8, 35.8%). Patients carrying this allele had a more destructive (Larsen wrist radiological index: mean +/- s.e.m., 2.1 +/- 0.2 vs 1.6 +/- 0.1, P = 0.005; Steinbrocker functional index: 2.4 +/- 0.1 vs 1.9 +/- 0.1, P = 0.002) and active disease (Ritchie articular index: 8.1 +/- 0.8 vs 5.3 +/- 0.6, P = 0.002; erythrocyte sedimentation rate (ESR): 36.6 +/- 2.9 mm/h vs 25.3 +/- 1.8 mm/h, P = 0.002). This contribution was independent from that of HLA DR4/DR1 to severity. IL-1Ra plasma levels adjusted to ESR values were significantly lower in IL-1B2 (+3954) positive than negative RA patients (1.0 +/- 0.1 vs 1.2 +/- 0.1 ng/ml, P = 0.01). This IL-1B (+3954) gene polymorphism may be an important marker for the severity of joint destruction in RA and is associated with an imbalance in IL-1Ra production. As this genetic association was independent and additive to the risk of HLA DR4/DR1 status, it could be a useful addition to HLA-DR4/1 as a genetic prognostic marker early in the course of the disease.

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.

Vascular endothelial growth factor production in polymyalgia rheumatica.

OBJECTIVE: To evaluate peripheral production and synovial expression of vascular endothelial growth factor (VEGF) in polymyalgia rheumatica (PMR). METHODS: Circulating levels of VEGF in PMR (serum concentration and in vitro release by peripheral blood mononuclear cells [PBMC]) were investigated by enzyme-linked immunosorbent assay. Local expression of VEGF in shoulder synovial tissue was investigated by immunohistochemical analysis. Investigations were performed in patients with active, untreated disease and in patients treated with corticosteroids. RESULTS: VEGF serum concentrations were significantly higher in untreated PMR patients than in normal control subjects. During steroid treatment, VEGF serum concentrations reached their lowest level after the sixth month of treatment. PBMC isolated from untreated PMR patients spontaneously secreted a higher amount of VEGF compared with PBMC from control subjects. Corticosteroid therapy did not affect the ability of PBMC to produce VEGF. Immunohistochemical staining performed on shoulder synovial tissue showed VEGF expression in both the lining layer and the sublining area. In 3 of 4 treated patients, no VEGF staining was found in synovial tissue during corticosteroid therapy. VEGF expression correlated with vessel density, but was not associated with alphavbeta3 and alphavbeta5 integrin expression. CONCLUSION: Peripheral and local VEGF releases have different responses to steroid treatment in PMR. The lack of response to corticosteroids by peripheral VEGF production supports the hypothesis that systemic involvement is dominant in PMR. At the synovial level, VEGF production is linked to vascular proliferation and is thus directly involved in the pathogenesis of synovitis.

IL-4 VNTR gene polymorphism in chronic polyarthritis. The rare allele is associated with protection against destruction.

OBJECTIVE: To evaluate the occurrence of variants of the interleukin 4 (IL-4) and IL-4 receptor (IL-4R) genes in patients with rheumatoid arthritis (RA) and their possible contribution to joint destruction. METHODS: Allelic frequencies for polymorphisms in the IL-4 [variable number of tandem repeat (VNTR) polymorphism in intron 3] and IL-4 receptor alpha chain (transition at nucleotide 1902) genes were assessed in 335 RA patients and 104 controls. Clinical indices of disease activity, disability and joint destruction and plasma levels of IL-1beta, IL-1Ra and sCD23 were assessed to evaluate a possible functional effect. RESULTS: Carriage of the rare IL-4(2) allele was higher in patients with non-destructive RA (40%) than in those with destructive RA (22.3%; odds ratio = 1.9, 95% confidence interval 1. 1-3.5, P = 0.0006) and in controls (26%, P = 0.002). Patients positive for this rare allele had significantly less joint destruction, assessed by the Larsen wrist index (P = 0.004) and a lower erythrocyte sedimentation rate (P = 0.04). A significantly higher carriage rate of IL-4(2) was seen in HLA-DR4/DR1(-) patients with non-destructive RA than in those with destructive RA. The IL-4 receptor polymorphism was not over-represented. Plasma levels of IL-1beta, IL-1Ra and sCD23, known to be modified by IL-4, were not different in individuals having different alleles. CONCLUSION: This IL-4 VNTR gene polymorphism may be a protective factor for severe joint destruction in RA that could be used as a prognostic marker early in the course of the disease.

[Familial variability in the clinical expression of hand-foot-mouth disease]. / Variabilità intrafamiliare della malattia mani-piedi-bocca.

Aim of the paper is to describe the variability of clinical symptoms in hand, foot and mouth disease, especially among patients belonging to the same family. In spring 1999, during an epidemic of hand, foot and mouth disease, nineteen cases were observed by the authors. In eight cases also some members of the family were affected. A great variability in the clinical expression of the disease, above all among the members of the same family were observed. No cases in children below twelve months or in elderly members of the family were found. Children below three years had more stressed general symptoms, but in no case hospitalization was necessary. Hand, foot and mouth disease does not always show vesicles and aphthae in the affected areas. Clinical expression can also be lacking, but in this case diagnosis can be made easy by the presence of an epidemic or of other cases in the same family.

Interleukin-1 cluster and tumor necrosis factor-alpha gene polymorphisms in polymyalgia rheumatica.

OBJECTIVE: To investigate whether polymorphisms in the interleukin (IL)-1 locus (human chrom. 2q13) and TNF-alpha gene are associated with susceptibility to or severity of polymyalgia rheumatica (PMR). METHODS: The study included 92 consecutive PMR patients diagnosed over a 5-year period who were prospectively followed-up for at least one year and 79 healthy controls over the age of 50 residing in the same area. All the patients and controls were Caucasians of Italian origin. We tested the allelic distribution of IL-1A (+4845), IL-B (-511), IL-B (+3954), IL-1RN Intron 2 VNTR and TNFA (-308). Frequencies were compared in the patient and control groups. RESULTS: A statistically significant association between PMR patients and the IL1RN*2 allele in the homozygous state was found [OR 8.46 (95% CI 1.05-68.31)]. The polymorphisms in the other genes of the IL-1 gene cluster did not reveal any association with PMR when compared with controls. A weak association between PMR patients and the TNF2 allele was also present [OR 2.09 (95% CI 1.0-4.17)]. None of the gene variants studied was associated with the disease severity of PMR. CONCLUSION: Our findings show that IL1RN*2 allele, particularly in the homozygous state, is associated with susceptibility to, but not with the severity of, PMR.