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Biomedical subjects

D Franciotta

Publications and source records attributed to D Franciotta.

At least 19 recordsLinked to original sources
PubMed2005

Postinfectious inflammatory disorders: subgroups based on prospective follow-up.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) refers to a monophasic acute multifocal inflammatory CNS disease. However, both relapsing and site-restricted variants, possibly associated with peripheral nervous system (PNS) involvement, are also observed, and a systematic classification is lacking. OBJECTIVE: To describe a cohort of postinfectious ADEM patients, to propose a classification based on clinical and instrumental features, and to identify subgroups of patients with different prognostic factors. METHODS: Inpatients of a Neurologic and Infectious Disease Clinic affected by postinfectious CNS syndrome consecutively admitted over 5 years were studied. RESULTS: Of 75 patients enrolled, 60 fulfilled criteria for ADEM after follow-up lasting from 24 months to 7 years. Based on lesion distribution, patients were classified as encephalitis (20%), myelitis (23.3%), encephalomyelitis (13.3%), encephalomyeloradiculoneuritis (26.7%), and myeloradiculoneuritis (16.7%). Thirty patients (50%) had a favorable outcome. Fifteen patients (25%) showed a relapsing course. Poor outcome was related with older age at onset, female gender, elevated CSF proteins, and spinal cord and PNS involvement. All but two patients received high-dose steroids as first-line treatment, with a positive response in 39 (67%). Ten of 19 nonresponders (53%) benefited from high-dose IV immunoglobulin; 9 of 10 had PNS involvement. The data were not controlled. CONCLUSIONS: A high prevalence of "atypical variants" was found in this series, with site-restricted damage or additional peripheral nervous system (PNS) involvement. Prognosis and response to steroids were generally good, except for some patient subgroups. In patients with PNS involvement and steroid failure, a favorable effect of IV immunoglobulin was observed.

Adult↗
PubMed2005

Long term disability and social status change after Guillain-Barré syndrome.

OBJECTIVE: Even if the majority of patients with Guillain-Barré syndrome (GBS) have a favourable functional outcome some residual motor and sensory signs and symptoms may remain. The aim of this study was to evaluate the long-term effect of GBS on daily life,working activities, hobbies and social status and the presence of residual symptoms. PATIENTS AND METHODS: Seventy patients with GBS enrolled in a case-control study were examined. Information on signs or symptoms during the acute phase of the disease was retrieved from medical records and an ad-hoc questionnaire administered during hospitalization. Patients were interviewed by phone 3 to 5 years after disease onset about residual symptoms and changes in daily living. Disability and handicap were assessed using the Hughes, Rankin and Rotterdam 9-items scale. RESULTS: At follow-up 45 patients (64 %) made a complete functional recovery; 19 patients (27%) had some minor limitations in daily life although they were able to perform all their activities independently while 6 (9 %) needed aid for some hours or continuously during the day. Nineteen patients (27 %) had, however, to make substantial changes in their job, hobbies or social activities. There was no significant correlation between clinical and laboratory features during the acute phase of GBS and outcome. CONCLUSIONS: Although over 90% of our GBS patients had a more or less complete functional recovery, almost 30% of them had to make substantial changes in daily life. These findings indicate that GBS still has a significant impact on patients' life which may go beyond their residual disability or impairment. Treatment of GBS should not be only aimed at improving patients' disability but also at limiting the impact of the disease on their social life.

Adult↗
PubMed2005

Analysis of Chlamydia pneumoniae-specific oligoclonal bands in multiple sclerosis and other neurologic diseases.

OBJECTIVE: Paired serum and cerebrospinal fluid (CSF) specimens were investigated for Chlamydia pneumoniae-specific oligoclonal bands (OCBs) to determine band specificity in multiple sclerosis (MS). MATERIAL AND METHODS: Serum and CSF samples were collected from patients with relapsing-remitting MS (n = 56), other inflammatory (n = 18) or non-inflammatory (n = 15) neurologic diseases, and from 10 healthy controls. OCBs were determined with affinity immunoblotting of C. pneumoniae-specific IgG onto antigen-coated nitrocellulose paper after protein separation with agarose isoelectric focusing. RESULTS: Chlamydia pneumoniae-specific OCBs were present in 5 of 56 patients with MS, and in 3 of 18 patients with other inflammatory neurologic diseases. CONCLUSIONS: The intrathecal production of C. pneumoniae-specific oligoclonal IgG occurs in a minority of patients with MS. This intrathecal anti-C. pneumoniae reactivity is likely part of a polyspecific humoral immune response in MS.

AIDS Dementia Complex↗
PubMed2004

Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects.

The authors used a liquid-phase radiobinding assay to measure serum anti-myelin oligodendrocyte protein (MOG) immunoglobulin (Ig) G in 87 patients with multiple sclerosis (MS), in 12 patients with encephalomyelitis, and in 47 healthy subjects. Anti-MOG IgM was determined in samples obtained at onset from 40 of 87 patients with MS and in control subjects. The frequency of positive samples with low titers of anti-MOG IgG (< or =5.7%) and IgM (< or =8.3%) was similar in all the groups and subgroups. Binding competition experiments showed that these antibodies had low affinity. Anti-MOG antibodies are not disease specific.

Adolescent↗
PubMed2004

Oligoclonal bands in Devic's neuromyelitis optica and multiple sclerosis: differences in repeated cerebrospinal fluid examinations.

We studied repeated cerebrospinal fluids of patients with Devic's neuromyelitis optica (NMO) and multiple sclerosis (MS). Variations of oligoclonal bands (OBs) had opposite trends in the two groups. In MS, OBs were detected in 399 of 411 patients (97%) and never disappeared. In NMO, OBs were detected in three of 11 patients (27%) and always disappeared. The hypothesis that NMO and MS follow distinct pathogenetic pathways is supported by our findings, which can be useful for the differentiation of NMO from MS.

Adult↗
PubMed2004

Biological markers in multiple sclerosis.

Advances in treatments for MS and the prospect of more (and increasingly effective) therapies make the search for disease-related biomarkers essential and urgent. Markers are needed for subtyping the disease itself, and for detecting disease-specific inflammation, axonal damage, remyelination and individual responses to therapies. The current dearth of reliable markers reflects our lack of knowledge of MS aetiology and pathogenesis. New technologies promise to boost understanding of MS and help identify biological markers for different aspects of the disease. The study of cerebrospinal fluid is of primary importance, as this bodily fluid is most likely to contain traces of products of the pathological/reparative processes occurring at the lesional level.

Axons↗
PubMed2003

Measurement of skeletal muscle mass in Duchenne muscular dystrophy: use of 24-h creatinine excretion.

Creatinine concentration in 24-h urine has been proposed as an indirect measure of body skeletal muscle mass (SMM). We attempted to correlate urinary creatinine levels with SMM in eight patients with Duchenne muscular dystrophy, a progressive disease in which the degree of muscle wasting parallels the rate of progression. Magnetic resonance imaging and a newly developed protocol for image analysis were used for the measurement of SMM. The patients ate a creatine-free diet for the week before urine collection. Creatinine was measured with an enzymatic-colorimetric method. Mean (+/-SD) SMM value was 5.4+/-2.5 kg and urine creatinine levels 205.8+/-96.4 mg/day. Daily urinary creatinine excretion did not correlate with SMM. The simple creatinine determination in urine cannot predict SMM in Duchenne muscular dystrophy.

Biomarkers↗
PubMed2003

Interferon gamma and interleukin 4 producing T cells in peripheral blood of multiple sclerosis patients undergoing immunomodulatory treatment.

Intracellular cytokine flow cytometry was used to analyse the percentages of interferon (IFN) gamma and interleukin (IL)-4 producing T cells in the peripheral blood of multiple sclerosis patients, before and after immunomodulatory treatment, and of healthy controls. After six months of treatment, different doses of IFN beta1a (Avonex or Rebif) decreased CD4+ (Th1, Th2) and CD8+ (Tc1) cells to a similar extent, without affecting the Th1/Th2 ratio. These T cell subsets were unmodified after nine months of glatiramer acetate (Copaxone) treatment, and after six day courses of high dose 6-methylprednisolone. The data suggest that IFN beta1a produces sustained downmodulation of IFN gamma and IL-4 producing T cells in vivo, which may contribute to its therapeutic efficacy; that glatiramer acetate possibly acts without altering non-specific cellular immunity; and that glucocorticoid induced lymphocytopenia does not affect the percentages of Th1, Th2, and Tc1 cells; at least in the periphery, none of the treatments caused a Th1 to Th2 shift that could account for their respective therapeutic effects.

Adjuvants, Immunologic↗
PubMed2003

An MRI study of Chlamydia pneumoniae infection in Italian multiple sclerosis patients.

We amplified sequences of the Chlamydia pneumoniae (CP) major-outer membrane protein in the cerebrospinal fluid (CSF) from 23 of 107 (21.5%) relapsing-remitting or secondary progressive multiple sclerosis (MS) patients and two of 77 (2.6%) patients with other neurological diseases (OND) (P = 0.00022). CP+ patients showed magnetic resonance imaging (MRI) evidence of more active disease (P = 0.02) compared to CP- MS patients and tended to have an anticipation of age at disease onset (32.3 +/- 12 versus 28.5 +/- 10 years; P = ns) causing a longer disease duration (7.5 +/- 5 versus 4.4 +/- 4 years; P = 0.016) at the time of clinical evaluation. These findings, although indirectly, suggest that CP infection of the central nervous system (CNS) might affect disease course in a subgroup of MS patients.

Adolescent↗
PubMed2001

Polymorphic markers in MHC class II/III region: a study on Italian patients with myasthenia gravis.

With an Italian case series of 81 Italian patients and 130 controls, we analysed associations between myasthenia gravis (MG) and genetic polymorphisms in the MHC class II/III region. Increases in the frequency of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype, which is likely part of the 8.1 ancestral haplotype, were maximal in females with early onset (EO) MG vs. controls [p<0.05, relative risk (RR)=9.9]. These patients showed neither a significantly high frequency of thymic hyperplasia, nor high levels of serum anti-acethylcholine receptor antibodies. The DRB1*03 allele was absent in patients with thymoma; however, in comparison with controls, occurrence of this marker was frequent in MG patients (p<0.005; RR=6.2), more frequent in females (p<0.005; RR=7.8) and most frequent in EOMG female patients (p<0.005; RR=15.1). Analysis of the TNF-B*1, C4A*Q0, C4B*1, DRB1*03 supratype and its recombinants showed that the MHC region between C4 and TNF might contain genes that influence susceptibility to MG in females. Polymorphic markers within the supratype, e.g. TNF-B*1 and C4A*Q0, might contribute to pathogenetically significant abnormalities in immune responses in a subset of female MG patients. The combined effect of other intervening genes cannot be excluded.

Adult↗
PubMed2001

Serum and CSF levels of MCP-1 and IP-10 in multiple sclerosis patients with acute and stable disease and undergoing immunomodulatory therapies.

The two chemokines, monocyte chemoattractant protein (MCP)-1 and gamma-interferon inducible protein (IP)-10, are thought to be involved in the pathogenesis of multiple sclerosis (MS). We measured MCP-1 and IP-10 levels in serum and CSF samples from 38 acute and 25 stable MS patients and from 40 controls. The latter consisted in patients with other inflammatory neurological diseases (OIND) or with non-inflammatory neurological diseases, and healthy controls. CSF MCP-1 levels exceeded those found in serum in all the patients studied as well as in healthy controls. CSF MCP-1 levels were significantly lower in acute MS [468+/-(S.E.M.) 18 pg/ml] than in stable MS (857+/-104 pg/ml). When detectable, serum and CSF IP-10 levels were significantly higher in acute MS (serum 331+/-66 pg/ml; CSF 118+/-16 pg/ml) than in stable MS (serum 69+/-7 pg/ml; CSF 25+/-2 pg/ml). Among OIND patients, those with HIV-1-associated dementia showed high serum and CSF levels of both MCP-1 and IP-10. Those with encephalitis showed high serum and CSF levels of IP-10 and CSF mononuclear pleiocytosis. We also evaluated the effects of 6-methylprednisolone or IFN-beta1a therapy on circulating MCP-1 and IP-10 levels. Neither MCP-1 nor IP-10 post-therapy levels varied significantly from baseline values. Our findings suggest that (a) MCP-1 could be constitutively produced within the brain; (b) MCP-1 and IP-10 CSF levels in acute MS vary significantly from those in stable MS, and these variations are inverse; and (c) current MS therapies do not modify circulating levels of MCP-1 and IP-10.

Acute Disease↗
PubMed2000

Interferon-beta treatment in multiple sclerosis patients decreases the number of circulating T cells producing interferon-gamma and interleukin-4.

Systemic administration of interferon (IFN)-beta has been recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The immunological mechanism by which IFN-beta ameliorates MS is still partially unknown. We measured the number of blood circulating CD4(+), CD4(-), CD8(+), and CD8(-) T cells secreting IFN-gamma and IL-4 in 26 RRMS patients followed for up to 9 months of an alternate day s.c. treatment with 8x16 IU of IFN-beta1b. Compared to pre-treatment values, a significant (P<0.05) reduction of CD4(+), CD4(-), CD8(+) and CD8(-) cells producing IFN-gamma and of CD4(+) and CD4(-) cells producing IL-4 was observed in MS patients. The IFN-beta-associated effect was evident soon after the beginning of the treatment and persisted for the entire follow-up period. We did not observe any effect of IFN-beta treatment on the percentage of IL-4-producing CD8(+) and CD8(-) cells nor in that of natural killer (NK) cells producing IFN-gamma. Our results show that IFN-beta treatment in MS patients induces a profound and persistent down-regulation of the number of circulating T cells secreting IFN-gamma and IL-4 thus suggesting a broader rather than a specific immunomodulatory effect of IFN-beta in MS.

Adjuvants, Immunologic↗
PubMed2000

Interferon-gamma and interleukin-4-producing T cells in peripheral blood of multiple sclerosis patients.

Pro- and anti-inflammatory cytokines are thought to participate in the development and regulation of autoimmunity in multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS). We analysed the percentage of interferon (IFN)-gamma and interleukin (IL)-4-producing cells in the peripheral blood of both active and stable MS patients, and of healthy controls. After short-term stimulation, cytokine-producing cells were intracellularly stained and sorted. Significantly lower percentages of IFN-gamma and IL-4-producing T cells were found in stable MS patients than in controls, and in active than in stable patients. The diminution affected CD4(+) (Th1, Th2) and CD8(+) (Tc1) phenotypes. Tc2 cells were not detected. The Th1/Th2 ratio did not differ in active and stable MS, nor in controls. The fact that Th2 and Tc1 cell percentages were higher in stable than in active MS possibly indicates that these cells play a downmodulating role in the immune response. In contrast, a role in exacerbating the immune response is not attributable to Th1 cells, given their reduction in acute MS. Our data do not support the hypothesis that MS is a Th1/Th2 paradigmatic disease; rather, they suggest that sequestration in the CNS, or activation-induced apoptosis (whether in vivo or in vitro) may explain reduced levels of IFN-gamma and IL-4-producing subsets in the peripheral blood of clinically acute patients.

Adolescent↗
PubMed1999

Relevance of interleukin 1 receptor antagonist intron 2 polymorphism in Italian MS patients.

The A1/A1 genotype of the anti-inflammatory cytokine interleukin 1 receptor antagonist (IL-1Ra) polymorphism was more frequent in 339 Italian MS patients than in healthy controls (HCs) (odds ratio = 1.83). A more aggressive disease course was also associated with A1+ genotypes and might reflect the reduced ability of mononuclear cell cultures of A1+ HCs to produce IL-1Ra. We conclude that an IL-1Ra gene polymorphism is associated with occurrence of disease and clinical course variability in Italian MS patients.

Adult↗
PubMed1999

TE671 cell-based ELISA for anti-acetylcholine receptor antibody determination in myasthenia gravis.

BACKGROUND: Acetylcholine receptor (AChR) from human muscles is the antigen used currently in radioimmunoprecipitation assays (RIPAs) for the determination of anti-AChR antibodies in the diagnosis of myasthenia gravis (MG). Our aim was to develop and validate an ELISA using TE671 cells as the source of AChR. METHODS: After TE671 cell homogenization, the crude AChR extract was used for plate coating. Anti-AChR antibodies were determined in 207 MG patients and in 77 controls. RESULTS: The mean intra- and interassay CVs (for two samples with different anti-AChR antibody concentrations) were 9.7% and 15.7%, respectively. Test sensitivity and specificity, for generalized MG, were 79.5% (95% confidence interval, 72.8-85.0%) and 96.1% (89.0-99.1%). The detection limit was 2 nmol/L. Anti-AChR antibody concentrations from 53 MG patients, as tested with our ELISA, showed good agreement with an RIPA with a mean difference (SD) of 1.0 (5.6) nmol/L. CONCLUSION: Our ELISA is a simple screening test for the diagnosis of MG and enables rapid and inexpensive patient follow-up.

Adolescent↗
PubMed1999

Tumor necrosis factor-alpha and its soluble receptors in plasma and cerebrospinal fluid of multiple sclerosis patients treated with methylprednisolone.

Demyelination is the main pathological feature of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. Tumor necrosis factor-alpha (TNF-alpha) can cause myelin damage and contribute to MS pathogenesis. We measured plasma and cerebrospinal fluid (CSF) levels of TNF-alpha and its soluble receptors, TNF-sRp55 and TNF-sRp75, in 18 patients with active MS, and in neurological and healthy controls. The same determinations were repeated on plasma and on CSF samples that were collected after the MS patients had ended a six-day treatment with high-dose methylprednisolone (MP). Pre- and post-treatment plasma and CSF TNF-alpha levels, when detectable, and those of TNF-sRp75, did not vary, and were similar to those of controls. CSF TNF-sRp55 levels were higher in acute MS patients than in controls. Post-treatment CSF TNF-sRp55 levels were higher than in the active phase of the disease. The MS patients, who clinically improved, tended to have the highest CSF TNF-sRp55 levels. The increase was due to intrathecal TNF-sRp55 synthesis. Although it is involved in MS pathogenesis, TNF-alpha is not detectable in plasma or in CSF samples from MS patients in various phases of the disease. A better marker of disease activity seems to be CSF TNF-sRp55 levels. The increased CSF levels of TNF-sRp55 in response to MP circumstantially suggest that this receptor could partially account for the beneficial effects of MP in acute MS.

Adult↗