Uterine artery Doppler in predicting pregnancy outcome in women with connective tissue disorders.
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Adult↗
Biomedical subjects
M Govoni
Publications and source records attributed to M Govoni.
Incidence and prevalence of systemic lupus erythematosus in a district of north Italy.
The objective of this study was to investigate the incidence and the prevalence of systemic lupus erythematosus (SLE) in an area of northeast Italy. We retrospectively examined all patients of 16 years and older of native Italian origin and resident in Ferrara district either admitted to hospital or referred to our outpatient clinic with a diagnosis of SLE determined between 1 January 1996 and 31 December 2002. SLE subjects were identified both by a search of hospital discharge code 710.0 according to the international classification of diseases-9 codes, and using a computerized search for this pathology code in the national health care system. Incidence and prevalence rates were calculated as number of cases per 100 000 inhabitants. Population data were based on the 2002 National Census. A total of 299 cases of SLE were identified. After a review of all cases by one experienced investigator, 98 were excluded because did not satisfied the 1982 revised criteria of the American College Rheumatology. Therefore, 201 patients had a definite diagnosis of SLE. The prevalence of SLE in the district was 57.9/100 000. The mean age at diagnosis was 41 years, the average duration of the disease from symptoms onset to diagnosis was 4.8 years and the female/male ratio 9:1. Annual incidence in 2000 was 2.01/100000, in 2001 1.15/100000 and in 2002 2.6/100000. This is the first study dealing with prevalence and incidence of SLE in an Italian district. Data obtained concerning prevalence, incidence, age at diagnoses and female predominance are in agreement with those published in literature.
Adult↗
Proton magnetic resonance spectroscopy may predict future brain lesions in SLE patients: a functional multi-imaging approach and follow up.
OBJECTIVE: To determine whether single photon emission tomography (SPECT) and magnetic resonance spectroscopy (1H-MRS) can predict the appearance of new lesions in systemic lupus erythematosus (SLE), detectable by magnetic resonance imaging (MRI). METHODS: (99)Tc(m)-HMPAO-SPECT, brain MRI, and (1)H-MRS were done in eight women with SLE (mean age 31.8 years; disease duration 5.5 years). NAA/Cho, NAA/Cre, and Cho/Cre ratios were assessed in hypoperfused and normoperfused areas detected by SPECT that were normal on MRI examination. Reference values were obtained in 20 normal healthy controls. In five patients, MRI was repeated four to six years after the first evaluation. RESULTS: Mean NAA/Cho and Cho/Cre ratios in hypoperfused and normoperfused frontal areas were, respectively, lower and higher than control. There were no differences in NAA/Cre ratios. Mean Cho/Cre ratios were increased in hypoperfused v normoperfused brain areas (mean (SD): 1.43 (0.27) v 1.00 (0.07); p<0.023). NAA/Cre ratios were not altered (2.18 (0.30) v 1.99 (0.28); p = 0.381). Three of five patients who had a second MRI had new lesions in areas previously abnormal on MRS and SPECT but normal on first MRI. One patient with positive MRI, SPECT, and MRS showed an increase in the number of MRI lesions; one patient with negative MRI, SPECT, and MRS did not show any new lesions. CONCLUSIONS: Abnormalities reflecting altered perfusion or neuronal-chemical changes can be demonstrated by functional imaging techniques even in the absence of morphological lesions detectable by MRI. The abnormal areas identified by SPECT and MRS may predict future parenchymal damage.
Adolescent↗
Beta thalassaemic trait and systemic lupus erythematosus.
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Adult↗
[Neuropsychiatric systemic lupus erythematosus: where are we now?].
When dealing with Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) there are still many controversial topics. In 1999 the American College of Rheumatology gave classification criteria for 19 clinical syndromes. However major problems are still related to low specificity of some of them such as headache, cognitive impairment or mood disorders. Even though a frequency of CNS involvement from 14 to 75% has been described, depending on both the population studied and the methodology of assessment, a lower frequency ranging from 21 to 28 % derived by larger case series seems more realistic. The introduction of the concept of "borderline cases", proposed by Italian Study Group for NP-SLE, is based both on clinical and instrumental evaluation and could represent a useful tool when dealing with conditions which do not fulfil ACR classification. Also the relationship between SLE activity and NP involvement is a debated issue. Concerning pathogenesis, it seems reasonable to consider multifactorial mechanisms related to antibody-mediated damage, antiphospholipid pro-thrombotic effect, non-inflammatory vasculopathy and cytokines mediated cytotoxycity. However, direct and unequivocal evidence for the implication of any of the above-mentioned mechanisms is still lacking. Although a wide range of neuroimaging tools have been used to evaluate CNS involvement, no single technique has proven to be definitive and, when dealing with a patient with suspected NPSLE, it is important to combine different diagnostic techniques. Due to the lack of effective imaging along with limitation in knowledge of underlying pathogenetic mechanisms and paucity of histopathologic findings, therapeutic approach in NPSLE remains a difficult issue and is currently based on personal experience. Italian Study Group for NP-SLE proposes the creation of a national registry on NPSLE to validate ACR classification criteria. Furthermore, the possibility to collect large series and stratifying them for each of the included neuro-psychiatric syndromes seems a good strategy for planning multicentric controlled therapeutic trials in the near future.
Cognition Disorders↗
Recent advances and future perspective in neuroimaging in neuropsychiatric systemic lupus erythematosus.
Involvement of the central nervous system (CNS) is one of the most important complications of systemic lupus erythematosus (SLE), occurring in 14-75% of SLE patients. Neurological and psychiatric involvement is mainly manifested as cerebrovascular disease, seizures, cognitive impairment, headaches and psychosis. However, diagnosis of brain involvement in SLE (i.e., neuropsychiatric lupus: NPSLE) as well as understanding of pathogenetic mechanisms still remains a difficult challenge. Although a wide range of neurodiagnostic tools have been used in the last decade to assess CNS involvement, no single technique has proven to be definitive or reliable. Since neurometabolic impairment, neurochemistry and perfusion abnormalities in NPSLE may precede anatomic lesions, new functional techniques such as magnetic resonance spectroscopy, diffusion and perfusion weighted imaging, and magnetization transfer imaging may be useful in order to indentify pathologic changes unrevealed by conventional imaging. So these new diagnostic tools could modify diagnostic and therapeutic approaches to this major unsolved problem, also shedding some light on the physiopathology of CNS disease in SLE.
Brain Mapping↗
Visceral leishmaniasis complicating a connective tissue disease: three case reports from Italy.
We report the occurrence of visceral leishmaniasis in three patients coming from the northern part of Italy treated with immunosuppressive drugs for different rheumatic conditions. This paper highlights the importance of adequate work-up in those patients presenting with serious clinical manifestations that can complicate, exacerbate or mimic a systemic connective tissue disorder. A prompt diagnosis is very important because visceral leishmaniasis has a high mortality and, if untreated, can be fatal.
Adult↗
In vitro evaluation of a new treatment for urinary tract infections caused by nitrate-reducing bacteria.
Dietary and endogenous nitrates are excreted in urine, and during infection with nitrate-reducing bacteria they are reduced to nitrite. At a low pH nitrite is converted to a variety of nitrogen oxides that are toxic to bacteria. We hypothesized that acidification of nitrite-rich infected urine would result in the killing of the nitrate-reducing bacteria. An Escherichia coli control strain and a mutant lacking nitrate reductase activity were preincubated in urine supplemented with sodium nitrate (0 to 10 mM) at pH 7.0. Then, the nitrite-containing bacterial culture was transferred (and diluted 1/10) to slightly acidic urine (pH 5 and 5.5) containing ascorbic acid (10 mM) and growth was monitored. The control strain produced nitrite in amounts related to the amount of nitrate added. This strain was killed when the culture was transferred to acidic urine. In contrast, the mutant that did not produce nitrite retained full viability. When control bacteria were grown in acidic urine with nitrate and ascorbic acid present from the start of the experiment, no inhibition of growth was noted. The MICs and minimal bactericidal concentrations of sodium nitrite-ascorbic acid in acidic urine were comparable to those of conventional antibiotics. Preincubation of nitrate-reducing E. coli in nitrate-rich urine leads to the accumulation of nitrite. Subsequent acidification of the urine results in generation of nitrogen oxides that are bactericidal. Killing, however, requires a sequential procedure in which the bacteria are first allowed to grow in a nitrate-rich neutral environment, later followed by acidification. We speculate that ingestion of nitrate followed some hours later by acidification of urine could be a new therapeutic strategy for the treatment of urinary tract infections.
Adult↗
[Semeiology of "early arthritis"].
The main problems related to "early arthritis" are making an accurate diagnosis and predicting the outcome. Clinical evidence strongly suggest that structural damage occur early and that early DMARD treatment improves the long term outcome of disease. Clinical criteria would facilitate early referral of the patients to establish the risk of persistent disease. From the "early arthritis clinics" (E.A.C.) experience has been developed a set of diagnostic criteria characterized by an excellent ability to discriminate, at the first visit, between self-limiting, persistent non-erosive and persistent erosive arthritis. The proposed set consists of 7 criteria: symptom duration (6 weeks - 6 months), morning stiffness of at least 1 hour, arthritis in >/= 3 joints, bilateral compression pain in the metatarsophalangeal joints, IgM-rheumatoid factor positivity, anti-cyclic-citrullinated-peptide antibody positivity and erosions on radiographs of the hands or feet. This approach requests an easy organization to simplify the access to sanitary services and represents an hard challenge both for rheumatologist and health administration.
Arthritis↗
Hearing loss evaluation of Sjögren's syndrome using distortion product otoacoustic emissions.
Sjögren's syndrome (SS) is a cell-mediated immune disorder primarily affecting the exocrine glands and hearing loss may be the first otological manifestation of this autoimmune disease. In order to assess the degree of sensorineural hearing loss in SS, 22 female patients were examined by means of standard audiometric tests (pure-tone audiometry, acoustic reflexes and impedance testing) and using distortion product otoacoustic emissions (DPOAEs). The results indicated that only 36.3% of the patients had mild sensorineural hearing loss. Hearing level and distortion product threshold estimates were found to be significantly correlated. No relationship was found between the duration of the disease and the DPOAE and hearing threshold variables. The data suggest that SS may not directly cause sensorineural hearing loss.
Adult↗
Anti-cE (Rh27), a rarely occurring antibody.
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Letter↗
CNS involvement in primary Sjögren's syndrome: prevalence, clinical aspects, diagnostic assessment and therapeutic approach.
Among the systemic manifestations of primary Sjögren's syndrome, neurological involvement is still an intriguing and debated issue. Although peripheral nervous system abnormalities are a well documented occurrence with a reported prevalence ranging from 10 to 20%, opinions differ as to the prevalence of CNS disease, with suggestions from 'nonexistent' to 'very common'. The lack of agreement probably reflects the different populations selected, different inclusion criteria and lack of rigorous epidemiological studies. In our experience, CNS involvement was detected in 7 of 87 (8%) unselected consecutive patients observed over a period of 5 years. The spectrum of CNS involvement is wide, including focal, diffuse, neuropsychiatric and spinal cord symptoms, frequently characterised by insidious onset, remitting course and, sometimes, progressive evolution. The diagnostic approach enabling early recognition of this complication relies on careful clinical assessment using history and physical examination combined with neuropsychological testing and instrumental, laboratory and imaging investigations such as magnetic resonance imaging, single photon emission computed tomography, electrophysiological testing and CSF analysis. The clinical picture often shows spontaneous remission, but when overt neurological symptoms occur or become progressive, therapeutic interventions with high dose corticosteroids and cytotoxic agents, such as intravenous cyclophosphamide pulse therapy, may be indicated.
Brain Diseases↗
Intercellular adhesion molecule-1 gene polymorphisms in Behçet's Disease.
OBJECTIVE: Intercellular adhesion molecule 1 (ICAM-1) is strongly expressed in vascular endothelial cells and perivascular inflammatory infiltrates in immunopathologic studies of Behçet's disease (BD) lesions. ICAM-1 genes may contribute to the inflammatory events responsible for the vessel damage in BD. We examined potential associations of ICAM-1 gene polymorphisms with BD susceptibility. METHODS: Case patients were 74 consecutive Italian patients with BD who were followed at the Bologna, Ferrara, Milano, Potenza, Prato, Reggio Emilia, and Trento rheumatology, ophthalmology, and neurology units over a 3 year period (1997-99) who satisfied the International Study Group criteria for BD; 228 healthy Italian blood donors from the same geographic areas were selected as control groups. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: The frequency of R241 was significantly higher in BD patients than in controls (20.3% vs 5.7%; p = 0.001, pcorr = 0.002, OR 4.2, 95% CI 1.9-9.3). The distribution of E/K 469 genotype was similar in patients and controls. Comparing patients with different clinical features, we found only a trend to higher frequency of R241 in patients with articular manifestations (21.4% vs 12.5%; p = 0.08). CONCLUSION: Our findings show that G/R 241 polymorphism of ICAM-1 is associated with BD susceptibility.
Adult↗
Association of MICA alleles and HLA-B51 in Italian patients with Behçet's disease.
OBJECTIVE: To evaluate the distribution of the MHC class I chain related gene A transmembrane (MICA-TM) alleles in Italian patients with Behçet's disease (BD), and to investigate the relative contribution of MICA alleles and HLA-B51 in the susceptibility and specific clinical features of BD. METHODS: A total of 69 consecutive Italian patients who satisfied the International Study Group criteria for BD were followed at rheumatology, ophthalmology, and neurology units during a 3 year period (1997-99). We selected 130 healthy subjects from the same geographic areas as controls. All patients and controls were examined for MICA microsatellite polymorphisms using polymerase chain reaction. Serological HLA class B51 typing was performed by a standard microlymphocytotoxicity technique. RESULTS: A strong association with HLA-B51 was observed in patients with BD (OR 5.7, 95% CI 2.8-11.3). The MICA-TM allele A6, in linkage disequilibrium with HLA-B51, was only slightly increased in patients compared to controls (60.9% vs 50.8%; p = NS). No significant associations between HLA-B51 or MICA-TM alleles and clinical subgroups, particularly central nervous system or eye involvement, were found. CONCLUSION: HLA-B51 is the most important susceptibility gene in BD. Association with MICA-A6, when it exists, is secondary to the strong linkage disequilibrium with HLA-B51.
Adult↗
Polynucleotide:adenosine glycosidase activity of saporin-L1: effect on various forms of mammalian DNA.
Saporin-L1 from the leaves of Saponaria officinalis belongs to a group of plant polynucleotide:adenosine glycosidases, known as ribosome-inactivating proteins due to their property of depurinating the major rRNA. Previous experiments indicated that saporin-L1 and other ribosome-inactivating proteins depurinate also DNA [Barbieri et al. (1994) Nature 372, 324; and (1996) Biochem. J. 319, 507-513]. Here we describe the effects of highly purified nuclease-free saporin-L1 on mammalian nuclear and mitochondrial DNA. Saporin-L1 had less activity on mitochondrial DNA than on nuclear DNA. A low, although significant, depurination of both chromatin and whole nuclei was observed. Mitochondrial nucleic acids are heavily depurinated in intact mitochondria, although the contribute of mtDNA to the deadenylation events is not known. The kinetic constants for several substrates were determined.
Animals↗
Nucleolar size indicates the rapidity of cell proliferation in cancer tissues.
In order to define the importance of the nucleolus in tumour pathology, the relationship between nucleolar size and function and tumour mass growth rate was studied in vivo. Ten established human cancer cell lines from colon carcinomas and neuroblastomas were inoculated subcutaneously in athymic mice and the doubling time (DT) of the xenograft tumour mass was calculated. The tumour DTs ranged from 3.2 to 15.7 days. Nucleolar size was evaluated in sections from formalin-fixed and paraffin-embedded tumour samples after silver staining for AgNOR proteins, using a specific image analysis system. The nucleolar area values were inversely related to the xenograft tumour mass DTs (r=-0.90; p<0.001). Nucleolar functional activity was also evaluated using rapid, intermediate, and slow growing tumours (one each). The values of RNA polymerase I activity measured in vitro were strongly related to the corresponding tumour DTs (r=-0. 99; p=0.03). The labelling indices (LIs) of three proliferation markers, MIB1, PCNA, and bromodeoxyuridine (BrdU), were also evaluated. As revealed by the MIB1 and PCNA LIs, almost all the cells of the xenograft tumours were cycling (86.6+/-5.6 SD and 95. 5+/-2.0 SD, respectively). Neither the MIB1, PCNA or BrdU LIs were related to the xenograft tumour mass DT, showing that the different growth rates of tumour xenografts were not due to different growth fractions, but were mainly related to different cell proliferation rates. The present data demonstrate that the size and function of the nucleolus are related to the cell proliferation rate of cancer tissue. Evaluation of nucleolar size after silver staining of AgNOR proteins represents a unique parameter for the histological assessment of rapidity of cell proliferation in tumour lesions.
Animals↗
The role of nuclear medicine in the evaluation of neuropsychiatric systemic lupus erythematosus: comment on the article by Sibbitt et al.
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Lupus Vasculitis, Central Nervous System↗
Prolonged remission state of refractory adult onset Still's disease following CD34-selected autologous peripheral blood stem cell transplantation.
We report a 38-year-old patient affected by refractory adult onset Still's disease who achieved a prolonged remission following CD34-selected ABMT. The conditioning regimen was based on the use of CY and anti-thymocyte globulin. A 3.0 and 2.0 log reduction of T (CD3+) and B (CD19+) lymphocytes, respectively, was obtained using a Ceprate device to select CD34+ cells from PBSC. In the pre-transplant period (1994-1998) the patient had a chronic persistent disease course with frequent and recurrent systemic articular flares and loss of some functional abilities, despite daily prednisone, pulses of CY and immunosuppressive therapy (CYA or MTX). At the time of ABMT the patient had become non-ambulatory. Within 3 weeks of ABMT the patient showed a marked decrease in joint swelling, and morning stiffness. Joint pain and systemic symptoms disappeared, the patient was able to walk and run and gained general well being. ESR, C-reactive protein and WBC count were significantly decreased, while Hb level increased. This partial remission persisted for at least 1 year after ABMT, although at 15 months of follow-up a reappearance of moderate synovitis in the knees and wrists was noted. Our data further showed that both patient BM microenvironment and stem-progenitor cell function (as assessed by LTC-IC assay) were damaged even 1 year after CD34-selected ABMT, suggesting that the persistence of these alterations could have facilitated the favorable outcome of the disease following ABMT. Bone Marrow Transplantation (2000) 25, 1307-1310.
Adult↗