Incidence of sex chromosome aneuploidy in a prenatal population: 27-year longitudinal study in Northern Italy.

OBJECTIVES: The availability of cell-free (cf) DNA as a prenatal screening tool affords an opportunity for non-invasive identification of sex chromosome aneuploidy (SCA). The aims of this longitudinal study were to investigate the evolution and frequency of both invasive prenatal diagnostic testing, using amniocentesis and chorionic villus sampling (CVS), and the detection of SCA in cfDNA samples from a large unselected cohort in Northern Italy. METHODS: The results of genetic testing from CVS and amniotic fluid samples received from public and private centers in Italy from 1995 to 2021 were collected. Chromosomal analysis was performed by routine Q-banding karyotype. Regression analyses and descriptive statistics were used to determine population data trends regarding the frequency of prenatal diagnostic testing and the identification of SCA, and these were compared with the changes in indication for prenatal diagnostic tests and available screening options. RESULTS: Over a period of 27 years, there were 13 939 526 recorded births and 231 227 invasive procedures were performed, resulting in the prenatal diagnosis of 933 SCAs. After the commercial introduction of cfDNA use in 2015, the frequency of invasive procedures decreased significantly (P = 0.03), while the frequency of prenatal SCA detection increased significantly (P = 0.007). Between 2016 and 2021, a high-risk cfDNA result was the indication for 31.4% of detected sex chromosome trisomies, second only to advanced maternal age. CONCLUSIONS: Our findings suggest that the inclusion of SCA in prenatal cfDNA screening tests can increase the prenatal diagnosis of affected individuals. As the benefits of early ascertainment are increasingly recognized, it is essential that healthcare providers are equipped with comprehensive and evidence-based information regarding the associated phenotypic differences and the availability of targeted effective interventions to improve neurodevelopmental and health outcomes for affected individuals. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

A high-resolution neutron spectroscopic camera for the SPARC tokamak based on the Jet European Torus deuterium-tritium experience.

Dedicated nuclear diagnostics have been designed, developed, and built within EUROFUSION enhancement programs in the last ten years for installation at the Joint European Torus and capable of operation in high power Deuterium-Tritium (DT) plasmas. The recent DT Experiment campaign, called DTE2, has been successfully carried out in the second half of 2021 and provides a unique opportunity to evaluate the performance of the new nuclear diagnostics and for an understanding of their behavior in the record high 14 MeV neutron yields (up to 4.7 × 1018 n/s) and total number of neutrons (up to 2 × 1019 n) achieved on a tokamak. In this work, we will focus on the 14 MeV high resolution neutron spectrometers based on artificial diamonds which, for the first time, have extensively been used to measure 14 MeV DT neutron spectra with unprecedented energy resolution (Full Width at Half Maximum of ≈1% at 14 MeV). The work will describe their long-term stability and operation over the DTE2 campaign as well as their performance as neutron spectrometers in terms of achieved energy resolution and high rate capability. This important experience will be used to outline the concept of a spectroscopic neutron camera for the SPARC tokamak. The proposed neutron camera will be the first one to feature the dual capability to measure (i) the 2.5 and 14 MeV neutron emissivity profile via the conventional neutron detectors based on liquid or plastics scintillators and (ii) the 14 MeV neutron spectral emission via the use of high-resolution diamond-based spectrometers. The new opportunities opened by the spectroscopic neutron camera to measure plasma parameters will be discussed.

The influence of risk factors on the onset and outcome of psychosis: What we learned from the GAP study.

The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The "jumping to conclusions" bias appeared to mediate the effect of lower IQ on vulnerability to psychosis. We confirmed that environmental factors operate on the background of polygenic risk, and that genetic and environment act together to push individuals over the threshold for manifesting the clinical disorder. The study demonstrated how biological pathways involved in the stress response (HPA axis and immune system) provide important mechanisms linking social risk factors to the development of psychotic symptoms. Further evidence implicating an immune/inflammatory component to psychosis came from our finding of complement dysregulation in FEP. Patients also showed an upregulation of the antimicrobial alpha-defensins, as well as differences in expression patterns of genes involved in NF-κB signaling and Cytokine Production. Being of African origin not only increased risk of onset but also of a more difficult course of illness. The malign effect of childhood adversity predicted a poorer outcome as did continued use of high potency cannabis.

A qualitative study of the acceptability of cognitive bias modification for paranoia (CBM-pa) in patients with psychosis.

BACKGROUND: Cognitive Bias Modification (CBM) has been used successfully as a computer-based intervention in disorders such as anxiety. However, CBM to modify interpretations of ambiguous information relevant to paranoia has not yet been tested. We conducted a qualitative investigation of a novel intervention called CBM for paranoia (CBM-pa) to examine its acceptability in patients with psychosis. METHODS: Eight participants with psychosis who completed CBM-pa were identified by purposive sampling and invited for a semi-structured interview to explore the facilitators and barriers to participation, optimum form of delivery, perceived usefulness of CBM-pa and their opinions on applying CBM-pa as a computerised intervention. The interviews were transcribed and analysed using thematic analysis by researchers working in collaboration with service users. RESULTS: Themes emerged relating to participants' perception about delivery, engagement, programme understanding, factors influencing experience, perceived impact and application of CBM-pa. CBM-pa was regarded as easy, straightforward and enjoyable. It was well-accepted among those we interviewed, who understood the procedure as a psychological intervention. Patients reported that it increased their capacity for adopting alternative interpretations of emotionally ambiguous scenarios. Although participants all agreed on the test-like nature of the current CBM-pa format, they considered that taking part in sessions had improved their overall wellbeing. Most of them valued the computer-based interface of CBM-pa but favoured the idea of combining CBM-pa with some form of human interaction. CONCLUSIONS: CBM-pa is an acceptable intervention that was well-received by our sample of patients with paranoia. The current findings reflect positively on the acceptability and experience of CBM-pa in the target population. Patient opinion supports further development and testing of CBM-pa as a possible adjunct treatment for paranoia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: 90749868 . Retrospectively registered on 12 May 2016.

Epithelial-to-mesenchymal transition in FHC-silenced cells: the role of CXCR4/CXCL12 axis.

BACKGROUND: Ferritin plays a central role in the intracellular iron metabolism; the molecule is a nanocage of 24 subunits of the heavy and light types. The heavy subunit (FHC) is provided of a ferroxidase activity and thus performs the key transformation of iron in a non-toxic form. Recently, it has been shown that FHC is also involved in additional not iron-related critical pathways including, among the others, p53 regulation, modulation of oncomiRNAs expression and chemokine signalling. Epithelial to mesenchymal transition (EMT) is a cellular mechanism by which the cell acquires a fibroblast-like phenotype along with a decreased adhesion and augmented motility. In this work we have focused our attention on the role of the FHC on EMT induction in the human cell lines MCF-7 and H460 to elucidate the underlying molecular mechanisms. METHODS: Targeted silencing of the FHC was performed by lentiviral-driven shRNA strategy. Reconstitution of the FHC gene product was obtained by full length FHC cDNA transfection with Lipofectamine 2000. MTT and cell count assays were used to evaluate cell viability and proliferation; cell migration capability was assayed by the wound-healing assay and transwell strategy. Quantification of the CXCR4 surface expression was performed by flow cytometry. RESULTS: Experimental data indicated that FHC-silenced MCF-7 and H460 cells (MCF-7shFHC, H460shFHC) acquire a mesenchymal phenotype, accompanied by a significant enhancement of their migratory and proliferative capacity. This shift is coupled to an increase in ROS production and by an activation of the CXCR4/CXCL12 signalling pathway. We present experimental data indicating that the cytosolic increase in ROS levels is responsible for the enhanced proliferation of FHC-silenced cells, while the higher migration rate is attributable to a dysregulation of the CXCR4/CXCL12 axis. CONCLUSIONS: Our findings indicate that induction of EMT, increased migration and survival depend, in MCF-7 and H460 cells, on the release of FHC control on two pathways, namely the iron/ROS metabolism and CXCR4/CXCL12 axis. Besides constituting a further confirmation of the multifunctional nature of FHC, this data also suggest that the analysis of FHC amount/function might be an important additional tool to predict tumor aggressiveness.

Equine hepacivirus persistent infection in a horse with chronic wasting.

Equine hepacivirus is the closest homologue of hepatitis C virus. Limited data on the clinical features of this infection are available. We report the identification of a horse with high-titre viremia by equine hepacivirus. Over a 15-month follow-up, the clinical signs and the viremic status persisted, suggesting a chronic evolution.

Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses.

BACKGROUND: Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated. METHOD: This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not. RESULTS: Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25-4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44-9.56); and patients of male gender (OR 3.13 95% CI 1.35-7.23). CONCLUSIONS: For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.

A comparison of the nutritional status between adult celiac patients on a long-term, strictly gluten-free diet and healthy subjects.

BACKGROUND/OBJECTIVES: There are conflicting data on the effect of a gluten-free diet (GFD) on the nutritional status of celiac patients. In the present study, we evaluated, in adult celiac patients, the influence of a long-term, strictly GFD on their nutritional status and compared it with matched healthy volunteers. SUBJECTS/METHODS: Our study included 39 celiac patients and 39 healthy volunteers. The body mass index (BMI) of patients and controls was evaluated at enrollment, while the patients' BMI before the GFD was retrieved from clinical records. In addition, at enrollment, in both groups, we compared BMI, fat mass (FM), bone mineral density (BMD), as well as their dietary intake, recorded on a 7-day diary. RESULTS: At the time of diagnosis, the majority of celiac patients (82.0%) had a normal BMI or were overweight, while 10.3% were malnourished. After the GFD, patients with a normal BMI showed a significant weight increase (P=0.002), but none of them switched in the overweight or obese category. Two (50%) of the four malnourished patients achieved a normal BMI. Controls and patients on a GFD had a similar BMI, FM, BMD and total calorie intake, but the amount of lipids and fiber intake was significantly different in the two groups (P=0.003 and P<0.0001, respectively). CONCLUSIONS: Our study demonstrates that a GFD is able to improve the nutritional status of celiac patients without inducing overweight or obesity. Our findings are related to a celiac population adopting a GFD based on a Mediterranean-type diet.

Impact of childhood adversities on specific symptom dimensions in first-episode psychosis.

BACKGROUND: The relationship between childhood adversity (CA) and psychotic disorder is well documented. As the adequacy of the current categorical diagnosis of psychosis is being increasingly questioned, we explored independent associations between different types of CA and specific psychotic symptom dimensions in a well-characterized sample of first-episode psychosis (FEP) patients. METHOD: This study involved 236 FEP cases aged 18-65 years who presented for the first time to psychiatric services in South London, UK. Psychopathology was assessed with the Positive and Negative Syndrome Scale and confirmatory factor analysis was used to evaluate the statistical fit of the Wallwork/Fortgang five-factor model of psychosis. CA prior to 17 years of age (physical abuse, sexual abuse, parental separation, parental death, and being taken into care) was retrospectively assessed using the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Childhood sexual abuse [ß = 0.96, 95% confidence interval (CI) 0.40-1.52], childhood physical abuse (ß = 0.48, 95% CI 0.03-0.93) and parental separation (ß = 0.60, 95% CI 0.10-1.11) showed significant associations with the positive dimension; while being taken into care was associated with the excited dimension (ß = 0.36, 95% CI 0.08-0.65), independent of the other types of CA. No significant associations were found between parental death and any of the symptom dimensions. CONCLUSIONS: A degree of specificity was found in the relationships between different types of CA and psychosis symptom dimensions in adulthood, suggesting that distinct pathways may be involved in the CA-psychosis association. These potentially different routes to developing psychosis merit further empirical and theoretical exploration.

The impact of childhood adversity on the persistence of psychotic symptoms: a systematic review and meta-analysis.

BACKGROUND: Evidence suggests that childhood adversity is associated with the development of psychotic experiences (PE), psychotic symptoms and disorders. However, less is known regarding the impact of early adversity on the persistence of PE and clinically relevant psychosis. Thus we conducted a systematic review of the association between childhood adversity and the course of PE and symptoms over time. METHOD: A systematic search of Medline, EMBASE and PsychINFO databases was undertaken to identify articles published between January 1956 and November 2014. We included studies conducted on general population samples, individuals at ultra-high risk (UHR) of psychosis, and patients with full-blown psychotic disorders. A meta-analysis was performed on a subgroup. RESULTS: A total of 20 studies were included. Of these, 17 reported positive associations between exposure to overall or specific subtypes of childhood adversity and persistence of PE or clinically relevant psychotic symptoms. A meta-analysis of nine studies yielded a weighted odds ratio of 1.76 [95% confidence interval (CI) 1.19-2.32, p < 0.001] for general population studies and 1.55 (95% CI 0.32-2.77, p = 0.007) for studies conducted using clinical populations. CONCLUSIONS: The available evidence is limited but tentatively suggests that reported exposure to adverse events in childhood is associated with persistence of PE and clinically relevant psychotic symptoms. This partially strengthens the case for addressing the consequences of early adversity in individuals presenting with psychotic phenomena to improve long-term outcomes. However, the heterogeneity of studies was high which urges caution in interpreting the results and highlights the need for more methodologically robust studies.

Do premorbid and post-onset cognitive functioning differ between schizophrenia and bipolar disorder? A systematic review and meta-analysis.

BACKGROUND: Schizophrenia (SZ) is characterized by a broad global cognitive impairment that precedes the onset of the disease. By contrast, some studies suggest that premorbid deficits are absent, or even reversed, in bipolar disorder (BD). However, studies have shown impairments in cognitive functioning after the illness onset in both disorders. The aim of this study was to systematically review and meta-analyze those studies that compared premorbid and/or post-onset global cognitive function between SZ and BD. METHOD: We searched Medline (PubMed), EMBASE and PsycINFO for studies where information on cognitive functioning was collected in both SZ and BD within the same study or using the same methods. RESULTS: Compared to healthy comparison groups, SZ patients showed a significant premorbid cognitive impairment [standardized mean difference (SMD) -0.597, 95% confidence interval (CI) -0.707 to -0.487, p < 0.0001] and a large post-onset impairment (SMD -1.369, 95% CI -1.578 to -1.160, p < 0.0001). We found small significant deficits in premorbid intellectual function in the BD group when this was assessed retrospectively (-0.147, 95% CI -0.238 to -0.056, p = 0.001) but not prospectively (-0.029, 95% CI -0.199 to + 0.142, p = 0.744), and moderate cognitive impairment after onset (SMD -0.623, 95% CI -0.717 to -0.529, p < 0.0001). CONCLUSIONS: SZ is characterized by significant deficits in premorbid intellectual function but the evidence regarding premorbid function in BD is equivocal. After illness onset, patients with both disorders seem to suffer a further decline in cognitive function but the magnitude of the impairment remains greater in SZ than in BD.

Gel-embedded niosomes: preparation, characterization and release studies of a new system for topical drug delivery.

In the present paper physical gels, prepared with two polysaccharides, Xanthan and Locust Bean Gum, and loaded with non-ionic surfactant vesicles, are described. The vesicles, composed by Tween20 and cholesterol or by Tween85 and Span20, were loaded with Monoammonium glycyrrhizinate for release experiments. Size and zeta (ζ)-potential of the vesicles were evaluated and the new systems were characterized by rheological and dynamo-mechanical measurements. For an appropriate comparison, a Carbopol gel and a commercial gel for topical applications were also tested. The new formulations showed mechanical properties comparable with those of the commercial product indicating their suitability for topical applications. In vitro release experiments showed that the polysaccharide network protects the integrity of the vesicles and leads to their slow release without disruption of the aggregated structures. Furthermore, being the vesicles composed of molecules possessing enhancing properties, the permeation of the loaded drugs topically delivered can be improved. Thus, the new systems combine the advantages of matrices for a modified release (polymeric component) and those of an easier permeability across the skin (vesicle components). Finally, shelf live experiments indicated that the tested gel/vesicle formulations were stable over 1 year with no need of preservatives.

[Anabolic therapy of induced osteoporosis in beta-thalassaemia major: case report and literature review]. / La terapia anabolica nella osteoporosi indotta da beta-talassemia major: caso clinico e revisione della letteratura.

Transfusion program and chelating therapy treatment has extended the life expectancy of thalassaemic patient; osteoporosis is considered an important cause of morbidity in adult patients who display increased fracture risk. This is a case report is about a thalassaemic young female with multiple spine fractures (D11, D12 e L2) and lumbar spine DEXA - T score = -3,1 and femoral = -3,4. This was in spite of therapy with alendronate 70 mg/week from January 2006 to September 2007. The patient was subsequentently treated for 18 months with 1-34 recombinant human parathyroid hormone and colecalciferol (100.000 U/monthly). After 4 months of therapy, the patient showed a decrease in spinal pain (Roland and Morris Disability Questionnaire) and an improvement of quality of life (Qualeffo) with normalization of osteocalcin and 25-OHcolecalciferol haematic levels after 6 months. Lumbar spine and femoral DEXA - Tscore, at 18 months, rose respectively to -2,5 and -2,4. Thalassaemia-induced osteoporosis is multifactorial and its management is very difficult. Bone marrow expansion, endocrine dysfunction, iron overload and genetic factors all seem to play important roles in the development of low bone mass in these patients. Bisphosfonates have been used in the management of thalassemia induced osteoporosis but there is no data about fracture risk. Anabolic therapy for thalassemic patients requests additional study on a large scale.

[Adult Scheuermann's disease as cause of mechanic dorsalgia]. / La malattia di Scheuermann dell'adulto come causa di dorsalgia meccanica.

Scheuermann's disease (SD) or vertebral osteochondrosis is the most frequent cause of non postural kyphosis and one of more frequent cause of adolescent's dorsalgia. The criteria for the diagnosis are: more than 5 degrees of wedging of at least three adjacent vertebrae at the apex of the kyphosis; a toracic kyphosis of more than 45 of Cobb's degree; Schmorl's nodes and endplates irregularities. In addition to classic SD, there are radiological alterations that remain asymptomatic for a long time to reveal in adult age: in that case it speaks of adult Scheuermann's disease (ASD). We considered the diagnosis of patients came from April 2006 to April 2007 on Day Hospital in our Clinic. ASD was diagnosed, besides, in 10 of these patients. 7 patients had previous diagnosis such as: dorsal Spondiloarthrosis (4 subjects); Osteoporosis with vertebral fractures (3 subjects). All these diagnosis was not confirmed by us. In case of chronic dorsalgia of adult, ASD is rarely considered as differential diagnosis. Besides, the vertebral dorsalgia, even in absence of red flags as fever, asthenia,hypersedimetry, functional loss and aching spinal processes to tapping, could hide a serious scene that lead us to be careful in the differential diagnosis, because of similar radiological pictures of the MSA to other pathology as spondylodiscitis, primitive or metastasic spinal tumors, and brittleness vertebral fractures.

Combined effect of Neridronate and specific antibiotic therapy in a case of tuberculous spondylodiscitis.

Because of the increased incidence of tuberculosis (TB) in recent years, infective spondylitis is still a major problem in the world. In skeletal TB the spine is the most often involved and lumbosacral spine involvement is rare. Nowadays early diagnosis and new medical treatment can reduce the incidence of the serious skeletal sequelae and the number of surgery procedures in spinal TB. We present a case of TB spondylodiscitis characterized by a rapid and progressive clinical and radiological improvement after treatment with Neridronate and chemotherapic drugs. Our data suggest that in the treatment of the TB spondylodiscitis the combined use of these drugs is a good alternative to stimulate bone reparative process to the chemotherapy alone. To our knowledge this is first case of a patient with TB discitis treated with Neridronate. Further studies are necessary to confirm the effectiveness of Neridronate treatment added to antiTB drugs in spondylodiscitis.

Cervical myelopathy caused by periodontoid synovial pannus in a patient with psoriatic arthritis: a case report.

The atlantoaxial subluxation and the formation of a synovial periodontoid pannus are associated with rheumatoid arthritis causing mechanical compression of the spinal cord and cervical myelopathy. Atlantoaxial subluxation is very rare in psoriatic arthritis (PsA). Even more rare is the formation of a periodontoid synovial pannus associated with PsA and signs of myelopathy. In this report, cervical myelopathy caused by periodontoid synovial pannus in PsA is described.

Pubic symphysis sclerosis in psoriatic arthritis. Case report.

Pubic symphysis sclerosis is a very interesting event in psoriatic arthritis (PsA). PsA is a cronical arthritis, associated with psoriasis, classified with seronegative spondyloarthrities. There are 5 clinical PsA patterns: an oligoarticular pattern, characterized by asymmetrical involvement of metacarpophalangeal and interphalangeal joints of hands and feet, as well as ankles and knees; a polyarticular pattern; a pattern characterized by involvement of distal interphalangeal joints; an arthritis mutilans pattern, characterized by acro-osteolysis of distal phalanxes; a pattern with spondylitic involvement. Although pubic involvement in PsA is not described in literature, a lot of authors describe the presence of erosive and/or sclerotic osteitis pubis in seronegative spondyloarthrities, without a more accurate subclassification. In seronegative spondyloarthrities sclerotic involvement of pubic symphysis has been described in patients suffering from ankylosing spondylitis for 5-10 years. A case of pubic symphysis sclerosis, evident on radiographs and detected also by magnetic resonance, which shows also a pattern of oedema and enhancement, with increased signal intensity on pubic symphysis in T2-weighted images, after the contrast agent was injected in the bone marrow, is reported in a woman affected by PsA. Pubic symphysis sclerosis is atypical in PsA and may be considered, by analogy with ankylosing spondylitis, the final result of repairing mechanisms of the previous erosive changes.

Arbuscular mycorrhizae increase the arsenic translocation factor in the As hyperaccumulating fern Pteris vittata L.

Phytoremediation techniques are receiving more attention as decontaminating strategies. Phytoextraction makes use of plants to transfer contaminants from soil to the aboveground biomass. This research is devoted to study the effects of arbuscular mycorrhizae (AM) on growth and As hyperaccumulation in the Chinese brake fern Pteris vittata. We grew for 45 days P. vittata sporophytes, infected or not infected with the AM fungi Glomus mosseae or Gigaspora margarita, in a hydroponic system on quartz sand. As-treated plants were weekly fed with 25 ppm As. The As treatment produced a dramatic increase of As concentration in pinnae and a much lower increase in roots of both mycorrhizal and control plants. Mycorrhization increased pinnae dry weight (DW) (G. margarita = G. mosseae) and leaf area (G. margarita > G. mosseae), strongly reduced root As concentration (G. mosseae > G. margarita), and increased the As translocation factor (G. mosseae > G. margarita). The concentration of phosphorus in pinnae and roots was enhanced by both fungi (G. margarita > G. mosseae). The quantitatively different effects of the two AM fungi on plant growth as well as on As and P distribution in the fern suggest that the As hyperaccumulation in P. vittata can be optimized by a careful choice of the symbiont.

[Fibromyalgic syndrome: new perspectives in rehabilitation and management. A review]. / La sindrome fibromialgica: le nuove prospettive riabilitativo-terapeutiche. Review.

Fibromyalgia is a chronic syndrome, characterized by widespread body pain and pain at specific tender points, whose etiology and pathogenesis is still unknown. Patient can also exhibit a range of other symptoms including irritable bowel syndrome, chest pain, anxiety, fatigue, sleep disturbance, headache. The prevalence of fibromyalgia ranges from 1-3% in the general population, and the condition is more common among female than males. Contrary to the situation a few years ago, the most widely accepted hypothesis now evoke central nervous system mechanisms, whose local functions could influence also periferical microvascular activity at tender points. There are many findings supporting the hypothesis of different endogenic and exogenic factors that lead to chronic local hypoxia in muscle tissue. Currently, therapy is polipragmatic and is aimed at reducing the pain. A range of medical treatment had been used to treat fibromyalgia. Pharmacological therapy aims to enhance the pain threshold and to support sleep. Nonpharmaceutical treatment modalities, such as exercise, massage, idrotherapy can be helpful. Future studies should investigate the possible benefits of new strategies that may combine the effects of hot pool water, stretching exercises, massage and relaxation benefits of balneotherapy.

Combination therapy with cyclosporine and methotrexate in patients with early rheumatoid arthritis soon inhibits TNFalpha production without decreasing TNFalpha mRNA levels. An in vivo and in vitro study.

OBJECTIVE: To evaluate the ability of two different combination therapies with prednisone (PDN), methotrexate (MTX) and cyclosporine (CSA) to modulate both TNFalpha transcription and production in early rheumatoid arthritis (RA). METHODS: 24 patients with early RA received a step-down bridge therapy with MTX and PDN (group A). Twelve patients out of the 24 randomly received also CSA (group B). Blood samples and peripheral blood mononuclear cells (PBMC) were collected at different times. TNFalpha levels were measured both in sera and in PBMC supernatants. TNFalpha mRNA was assessed by use of RT-PCR. RESULTS: 10 patients in group A and 9 in group B improved. At baseline, RA patients serum TNFalpha levels were increased compared to controls (p < 0.001) and did not correlate with clinical and serological parameters. These levels decreased within the first month of therapy in both groups, the lower levels being observed in the sera of CSA treated patients. After 30 days of therapy, TNFalpha levels in group B supernatants were significantly lower than those observed in group A, both after 24 and 48 hours of PHA stimulation (p < 0.03 and p < 0.05 respectively). TNFalpha mRNA levels never differed between patients and controls, independently of both the clinical picture and the assigned therapy. CONCLUSION: The addition of CSA to a treatment regimen of PDN + MTX lowers TNFalpha production in vitro without decreasing TNFalpha mRNA expression. This effect could help to induce early immunosoppressive and therapeutic effects during RA.