Novel autoantibodies in rheumatoid arthritis.

Rheumatoid factor and antibodies against cyclic citrullinated peptides represent a diagnostic hallmark in rheumatoid arthritis (RA). However, over the last decades many other autoantibodies have been identified. Several proteins can trigger an aberrant autoimmune response in their native form while others acquire this feature after post-translational modifications such as citrullination, carbamylation or acetylation. It is of interest that also the enzymes catalyzing such post-translational modifications (e.g. the protein arginine deiminases) can transform themselves into autoantibodies in RA. The purpose of this review article is to provide an overview of relevant literature published over the last years regarding novel autoantibodies and their possible diagnostic and prognostic significance in RA.

Extra-articular rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly affects the joints, though a consistent proportion of patients may also display extra articular manifestations (EAMs). From rheumatoid nodules to interstitial lung disease, from cardiovascular events to vasculitis, the spectrum of EAMs encompasses various conditions with different prognoses. EAMs may also occur as first RA manifestation, therefore the coordination with other health professionals, including general practitioners, is needed. The aim of this article is to provide an overview on EAMs in RA with particular focus on the recognised risk factors and the available recommendations for managing them, as well as comorbidities in RA patients.

Role of Inflammatory Diseases in Hypertension.

Chronic inflammatory diseases (CID) are characterized by an increased risk of cardiovascular (CV) morbidity and mortality. Several mechanisms, including early acceleration of subclinical atherosclerotic damage, inflammatory markers and immune system deregulation factors, have been demonstrated to strictly interplay for development and progression of atherosclerosis. Moreover, traditional CV risk factors are likely to explain at least some of the excess of CV risk in these patients. Among traditional CV risk factors, compelling evidence suggests a higher incidence and prevalence of hypertension in patients with CID in comparison to the general population. Moreover, hypertension represents an important predictor of CV events in these patients. Pathogenic mechanisms underlying the rise of blood pressure in CID are multifactorial and still poorly investigated. Indeed, multiple disease-related factors may affect blood pressure control in these patients and hypertension may affect disease prognosis and increase CV risk. Better knowledge of the complex interplay between hypertension and CID will be important to elucidate pathogenic mechanisms and to improve CV outcome in these patients. Aim of this review is to highlight available evidence on the relationship between hypertension and CID and to elucidate the multiple factors that may affect blood pressure control in these disorders.

Metabolomics comparison of red cells stored in four additive solutions reveals differences in citrate anticoagulant permeability and metabolism.

BACKGROUND AND OBJECTIVES: Metabolomics studies have revealed transition points in metabolic signatures of red cells during storage in SAGM, whose clinical significance is unclear. We set out to investigate whether these transition points occur independent of storage media and define differences in the metabolism of red cells in additive solutions. MATERIALS AND METHODS: Red cell concentrates were stored in SAGM, AS-1, AS-3 or PAGGSM, and sampled fourteen times spanning Day 1-46. Following quality control, the samples were split into extracellular and intracellular aliquots. These were analysed with ultra-high-performance liquid chromatography coupled to mass spectrometry analysis affording quantitative metabolic profiles of both intra- and extracellular red cell metabolites. RESULTS: Differences were observed in glycolysis, purine salvage, glutathione synthesis and citrate metabolism on account of the storage solutions. Donor variability however hindered the accurate characterization of metabolic transition time-points. Intracellular citrate concentrations were increased in red cells stored in AS-3 and PAGGSM media. The metabolism of citrate in red cells in SAGM was subsequently confirmed using 13 C citrate isotope labelling and shown to originate from citrate anticoagulant. CONCLUSION: Metabolic signatures that discriminate between 'fresh' and 'old' stored red cells are dependent upon additive solutions. Specifically, the incorporation and metabolism of citrate in additive solutions with lower chloride ion concentration is altered and impacts glycolysis.

Treatment of traumatic dental injuries: evaluation of knowledge among Italian dentists.

AIM: The aim of this study was to evaluate the degree of knowledge in the management of different scenarios of dental trauma in a population of Italian dentists. MATERIALS AND METHODS: A closed-ended questionnaire consisting of 5 clinical cases of common traumatic dental injuries was asked to be filled out by dentists in the area of Milan, Italy. A total of 500 questionnaires were collected; after a descriptive analysis of the population, results of correct answers were expressed in frequency distribution and computed in percentages. To examine possible associations between the level of knowledge for each question (number/percentage of correct answers) and independent variables of the population (sex, number of years after graduation, attendance of dental trauma courses, type of clinical activity) appropriate correlation tests were performed (Pearson chi-square, or Fisher's exact; level of significance = 0.05) for identification of statistically significant differences. RESULTS: More than 75% of participants answered correctly to the questions regarding crown fracture and extrusive luxation injuries; only 40% of dentists responded correctly about the duration and type of splinting following avulsion; 60% of participants incorrectly chose immediate invasive therapies (tooth extraction or endodontic procedures) for horizontal middle-root fracture. There was a trend towards slightly better knowledge (in 7 out of 9 questions) for dentists 1) working in hospitals and 2) who had attended a post-graduate course in traumatology. CONCLUSION: The level of knowledge in the group of dentists considered was heterogeneous; problems in the management of traumatic dental injuries were restricted to specific clinical cases and topics.

Development and validation of a LC/MS/MS method for simultaneous quantification of oxcarbazepine and its main metabolites in human serum.

A fast, sensitive and specific LC/MS/MS method for the simultaneous analysis of oxcarbazepine (OXC), 10-hydroxycarbazepine (MHD) and trans-diol-carbazepine (DHD), in human serum, has been developed and validated. Serum drugs were extracted by C8 solid-phase cartridges (SPE) and separated in less than 3 min on a C18 reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring. Calibration curves, obtained on two ranges of concentration (0.78-50 mg/L for MHD and 0.078-5.0 mg/L for OXC and DHD), showed correlation coefficients (r) better than 0.997. Within day and between days quality controls imprecision, as CV%, ranged from 0.3 to 4.6% and from 1.9 to 5.8%, respectively. Cyheptamide (CYE) was used as internal standard. No detectable carry-over and no relevant cross-talk and matrix effect occurred. Samples from 24 treated patients were analysed and drug serum concentrations obtained by this method are in agreement with those of other methods and also are well correlated (r=0.88) in comparison to our routine HPLC-UV method. Based on the analytical results and short run time, the method is suitable to support routine analysis of therapeutic drugs monitoring from human serum of treated patients or for pharmacokinetic studies.

Understanding the insulating phase in colossal magnetoresistance manganites: shortening of the Jahn-Teller long-bond across the phase diagram of La1-xCaxMnO3.

The detailed evolution of the magnitude of the local Jahn-Teller (JT) distortion in La(1-x)Ca(x)MnO3 is obtained across the phase diagram for 0< or =x< or =0.5 from high-quality neutron diffraction data using the atomic pair distribution function method. A local JT distortion is observed in the insulating phase for all Ca concentrations studied. However, in contrast with earlier local structure studies, its magnitude is not constant, but decreases continuously with increasing Ca content. This observation is at odds with a simple small-polaron picture for the insulating state.

[Incidence of occupational accident in Sicilian University Hospital]. / Andamento del fenomeno infortunistico nel quinquennio 2002-06 in una Azienda Universitaria Ospedaliera Sicliana.

The evolution of the disease accident has been analysed in a University Hospital in Sicily (approx. 2500 employees/year) for the time period between 2002 and 2006. The industrial injuries index has shown a swing in course (from a value of 3.80% in 2002 to 5.17% in 2003 to 4.49% in 2004), affecting the categories of nurses and health social workers most. The phenomenon shows a constant course within the same period for medical staff, technical assistants and administrative staff. Biological risk industrial injuries have the highest frequency compared to all others (62.5% in 2002 down to 42.3% in 2006). The most interesting datum is the relative scarce entity of the phenomenon when compared to other similar hospital situations and the progressive reduction of biological risk incidents.

["Barber's hair sinus": new clinical observation]. / "Barber's hair sinus": recente osservazione clinica.

The AA describe an unusual case of pilonidal sinus in a barber. The clinical analysis showed the presence, in all digital spaces, of erythemateous areas irregularly infiltrated by small fistular tracts and a keratinization area. In the first interdigital space of the left hand, the discharge of a bristle from the apex of a papule was also visibly evident. The histological examination showed the presence of a foreign body granuloma, with giant cells, lymphocyte and plasma cells, centered on a bristle fragment immersed in a collagenous matrix with abundant keratine, skin thickening and fibrous dermis. Using a probe, it was possible to follow the fistular path and obtain the discharge of several hair fragments, conglutinated by corneous scales, but it was not possible to achieve clinical cure of the lesion. The solution to the problem therefore required surgical therapy.

[Usefulness of HbCO level determination in chronic exposure to low environmental concentrations of CO. Study of a group of exposed workers]. / Utilità del dosaggio della HbCO nell'esposizione cronica a basse concentrazioni ambientali di CO. Indagine su un campione di esposti.

This research is based on consideration that HbCO sampling, routinely effected on environmental physician demand for workers' biological monitoring, has a low significance. To confirm or reject this statement, we considered two population groups: n. 583 exposed workers and n. 334 not exposed subjects as control group. The habit of smoking (either as number of cigarettes or as time elapsed between the drawn and the last smoked cigarette) was obviously considered on both groups. The results have shown that it isn't possible to acknowledge the effect of a low CO occupational pollution by using HbCO haematic sampling. The A.A. affirm that it's due to low pollution level in work place and to wrong praxis of haematic sampling performed after a long time from the end of working turn. The research showed a direct correlation between HbCO level and smoking habit and a strong association between time elapsed from last smoked cigarette and haematic sampling.

[Shift-work seniority increases the severity of sleep disorders. Comparison of different categories of shift-workers]. / L'anzianità di turnismo aumenta la gravità dei disturbi del sonno. Confronto fra diverse categorie di turnisti.

Shift-work disrupts the sleep-wake cycle and could bring about sleep disorders and excessive daytime sleepiness. We studied two samples of shift-workers, a group of 178 nurses and one of 174 police officers, all working in the town of Palermo (Italy); their answers to a sleep disorder questionnaire were scored and added in order to create a Sleep Disorder Score (SDS). The SDS cut-off value, discrimining pathological values from physiological ones, was settled a-priori. In both groups SDS did not depend on sex, age, weight, height nor on working seniority, but it increased non linearly (cubic form) with shift-work seniority. In nurses this mathematical description of SDS exceeded the cut-off value after 15 years of shift-work seniority; in police officers it settled asymptotically under the critical value. This could be ascribable both to the different composition in sex of the two samples (nurses: 49% F-51% M vs. police officers: 6% F-94% M) both to the self-selection process that seems to undergo police officers (nurses do not leave shift-work because of salary incentives).

Trinucleotide microsatellites in Norway spruce ( Picea abies): their features and the development of molecular markers.

Trinucleotide microsatellites have proven to be the markers of choice in human genetic analysis because they are easier to genotype than dinucleotides. Their development can be more time-consuming due to their lower abundance in the genome. We isolated trinucleotide microsatellites in Norway spruce ( Picea abies K.) using an enrichment procedure for the genomic-library construction. Here we report on the characterisation of 85 ATC microsatellite-containing clones, from which 39 markers were developed. Many of the clones showed the occurrence of tandem repeats of higher order than the trinucleotide ones, often resembling minisatellite repeats. The sequencing of a sample of the alleles at one of the loci revealed size homoplasy due to base substitutions within the microsatellite region. The presence of ATC motifs within repetitive sequence families was observed. We found a significant relationship between the level of polymorphism and the length of the microsatellite. The levels of variability for ATC trinucleotide markers were lower than those for dinucleotides, both when tested on all loci in a set of six individuals and on a subset of loci in four natural populations. This difference is most likely attributable to lower mutation rates for trinucleotide than for dinucleotide loci. The availability of markers with different mutation rates allows one to select the proper marker set to investigate population processes on different time scales.

Towards second-generation STS (sequence-tagged sites) linkage maps in conifers: a genetic map of Norway spruce (Picea abies K.).

Genetic linkage maps have been produced for a wide range of organisms during the last decade, thanks to the increasing availability of molecular markers. The use of microsatellites (or Simple Sequence Repeats, SSRs) as genetic markers has led to the construction of "second-generation" genetic maps for humans, mouse and other organisms of major importance. We constructed a second-generation single-tree genetic linkage map of Norway spruce (Picea abies K.) using a panel of 72 haploid megagametophytes with a total of 447 segregating bands [366 Amplified Fragment Length Polymorphisms (AFLPs), 20 Selective Amplification of Microsatellite Polymorphic Loci (SAMPLs) and 61 SSRs, each single band being treated initially as a dominant marker]. Four hundred and thirteen markers were mapped in 29 linkage groups (including triplets and doublets) covering a genetic length of 2198.3 cM, which represents 77.4% of the estimated genome length of Picea abies (approximately 2839 cM). The map is still far from coalescing into the expected 12 chromosomal linkage groups of Norway spruce (2n = 2x = 24). A possible explanation for this comes from the observed non-random distribution of markers in the framework map. Thirty-eight SSR marker loci could be mapped onto 19 linkage groups. This set of highly informative Sequence Tagged Sites (STSs) can be used in many aspects of genetic analysis of forest trees, such as marker-assisted selection, QTL mapping, positional cloning, gene flow analysis, mating system analysis and genetic diversity studies.

[Primary prevention: environmental modification and changes in chronic respiratory pathology in workers in a metallurgical industry]. / In tema di prevenzione primaria: modifiche ambientali e variazioni della patologia respiratoria cronica in lavoratori di una industria metalmeccanica.

The authors analyse the data connected with chronic pulmonary diseases (mainly bronchitis) of two groups of workers, both belonging to the same metallurgical factory. The data is taken in two different periods, before and after the introduction of measures for primary prevention in the factory. The results confirm that the overall cases of pulmonary diseases are greatly reduced by a correct improvement in the working environment. Moreover, they confirm that a dangerous working environment affects the breathing system more prominently then other factors such as smoking, etc.

[Possible etiologic role of occupational exposure to arsenic anhydride in a case of bladder carcinoma]. / Possible ruolo eziologico dell'esposizione professionale ad anidride arseniosa in un caso di carcinoma vescicale.

It has long been known that occupational or environmental exposure to arsenic (As) may cause skin and lung cancer. Moreover, several epidemiological studies on populations exposed to inorganic As by ingestion indicate an increased risk for cancer at other sites and, particularly, for bladder cancer. We describe the case of a petrol chemical worker, who died of metastasized bladder cancer at the age of 52, after being employed for over 30 years in a hydrogen production unit. Analysis of the technological cycle and biological monitoring data revealed an excessive, prolonged exposure to arsenic trioxide (As2O3) vapours and fumes; a solution of this compound was utilized to absorb the CO2 produced by oxidation of the synthesis gas. Careful anamnesis indicated a prolonged contact between the carcinogen and the bladder mucosa, due to the presence of severe urethral stenosis with chronic urinary obstruction. It also appears likely that synergism between As exposure and smoking (5-10 cigarettes per day until 46 years) occurred. This case suggests the opportunity to extend to the occupational setting future epidemiological research on the relationship between inorganic As exposure and bladder cancer.

[Myoclonus of focal action and localized hemispheric lesion. A polygraphic and pharmacological study]. / Myoclonus d'action focal et lésion hémisphérique localisée. Etude polygraphique et pharmacologique.

Authors report a case of focal action myoclonus due to a localized hemispheric lesion. The woman had cardiac arrest complicated by ischemic stroke involving the left parietal region. Action myoclonus of the inferior right limb was the sole residual complaint, provoked by movement and maintenance of posture. Patient noted that myoclonus was worsened by carbamazepine and vigabatrin. EEG-EMG polygraphic study demonstrated action myoclonus and showed a particular EEG activity consisting in a volley of spikes on the vertex region during the right inferior limb movements. Contralateral movements did not elicit this activity. Pharmacological response to clonazepam, piracetam and alcohol was studied. A marked improvement of myoclonus was obtained with alcohol. Pathophysiology of this exceptional form of cortical action myoclonus is discussed.

Early modification of stretch reflex in Parkinson's disease.

We stretched quadriceps femoris in healthy subjects and in patients with a recent diagnosis of PD in order to assess whether modifications of the long-latency component of the stretch reflex is an early event in the course of Parkinson's disease (PD). We found a modified mechanical and electromyographic (EMG) behavior in stretching relaxed muscles of patients while voluntary activation greatly reduced differences between normal and Parkinsonian subjects, suggesting that a lower threshold of the response is an early sign in PD.

Stretch reflex of quadriceps femoris in normal man: methodological considerations and normative data.

Short- and long-latency responses to stretching have been evoked in various muscles in the healthy subject. The quadriceps femoris, however, has never been investigated in this connection, despite its functional importance. We studied its stretch reflex in 17 healthy subjects with a torque motor to determine its morphological features in relation to the level of background EMG activity, the stretching velocity and duration and the instructions given to the subject. Two bursts of EMG activity were constantly evoked when the muscle was voluntarily activated. Response magnitude was proportional to the background activity and displacement velocity. Short stretching evoked only one EMG burst. These findings are similar to those from other muscles. Intra-individual variability was evaluated repeating the experiment in the same session without changing position of the electrodes, and then after two months. The long-latency response showed a good intra-individual reproducibility.

Stretch reflex of quadriceps femoris and its relation to rigidity in Parkinson's disease.

Much evidence suggests that parkinsonian rigidity is due to hyperactivity of a reflex arc. While tendon jerk and H reflex are not modified in Parkinson's disease (PD), the long-latency component of stretch reflex (LLR) shows an increased size in PD. It has been proposed that this modification could account for rigidity. We studied in 14 PD patients and 8 normal subjects the stretch reflex of the quadriceps femoris. The muscle was stretched by a torque motor in two experimental sets: at rest and with voluntary background activity. Latency, duration and size of the reflex were compared in two groups; correlation between size of the reflex and rigidity was investigated. A lower threshold for the reflex was found in PD patients in trials at rest, and LLR showed increased size and duration in trials with background activity. No clear relationships between these data and rigidity were demonstrated.

[Normal spirometric values in the Sicilian population]. / Valori spirometrici "normali" nella popolazione siciliana.

Principal spirometric parameters have been measured in a sample group of 1641 male subjects. Due to the significant difference in values often found when using the standards proposed by CECA (1983) (particularly in the medico-legal field) in order to obtain reference values as close as possible to the local norm the chosen subjects are clinically and functionally healthy and come from different parts of Sicily. The regression plots obtained using three independent variables (age, weight, height) other than demonstrating a good affinity with the original sample and an elevated predictivity level, underline the difference between obtained reference values and European ones (higher for VC and FEV 1; lower for FRC and RV) even though evolutive trend and ageing overlap. The above mentioned difference, found also for some parameters (VC and FEV 1) using normal Italian standards can be explained; not only by different evaluations of normal conditions, respiratory risk, smoking etc., but also by the existence of a different ethnic constitution which influences in various ways the ventilatory parameters.