Beneficial effect of low dose G-CSF and cyclosporin-A in a case of chronic neutropenia.
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Autoimmune Diseases↗
Biomedical subjects
V Martinelli
Publications and source records attributed to V Martinelli.
Cumulative effect of a weekly low dose of interferon beta 1a on standard and triple dose contrast-enhanced MRI from multiple sclerosis patients.
In patients with multiple sclerosis (MS), we assessed the short- and long-term effects of a weekly low dose of recombinant human interferon beta 1a (rh-IFN beta 1a) on the development of new magnetic resonance imaging (MRI) lesions enhancing at different gadolinium-DTPA (Gd) doses. Every 4 weeks, standard dose (SD) (0.1 mmol/kg of Gd) and triple dose (TD) (0.3 mmol/kg of Gd) Gd-enhanced brain MRI scans were obtained from 18 patients with relapsing-remitting MS for 3 months before treatment, 4 months after treatment initiation (treatment period [TP] I) and 4 months after 1 year of treatment (TP II) with 44 microg of rh-IFN beta 1a subcutaneously, once a week. The mean numbers of new enhancing lesions/patient/month were 1.4 (baseline), 1.1 (TP I) and 0.7 (TP II) on SD scans and 2.4 (baseline), 1.3 (TP I) and 0.8 (TP II) on TD scans. On average, treatment decreased the rate of new enhancing lesion appearance by 24% (SD scans) and 45% (TD scans) during TP I and by 52% (SD scans) and 66% (TD scans) during TP II. This study indicates that the effect of 44 microg of rh-IFN beta 1a given once a week on MRI-monitored MS activity increases over time. It also suggests that TD MRI is useful in detecting early treatment effect, that would otherwise be missed.
Adjuvants, Immunologic↗
A multiparametric MRI study of frontal lobe dementia in multiple sclerosis.
Previous studies achieved conflicting results when correlating magnetic resonance imaging (MRI) abnormalities and cognitive impairment in multiple sclerosis (MS) patients. Recently, the estimation of MS lesion load on T1-weighted images and the analysis of magnetization transfer ratio (MTR) histograms, increased the degree of the correlation between physical disability and MRI findings in MS. We assessed the relationship of conventional and non-conventional MRI-derived measures with frontal lobe dementia in MS. Dual echo, T1-weighted and MT MRI scans of the brain were obtained in 11 MS patients with and in 11 without frontal lobe dementia, matched for age, sex, education and disability. Total (TLL) and frontal (FLL) lesion loads were assessed from T2- and T1-weighted scans. MTR histogram analysis was performed for the whole brain, the frontal lobe and the cerebellum. Median TLL and FLL were significantly higher in cognitively impaired patients on both T2- and T1-weighted scans. The MRI measure that better discriminated the two groups of patients was T1-weighted TLL (median values were 19.1 ml for demented and 1.9 ml for non-demented patients, P=0.006). Average MTR, peak height and location of overall brain and frontal lobe histograms were significantly lower for cognitively impaired than for cognitively intact patients (P values ranged from 0.0001 to 0.001). Cerebellar MTR histogram metrics did not significantly differ in patients with and without cognitive decline. The presence of cognitive decline in MS is associated with the extent and pathological severity of brain MRI abnormalities.
Dementia↗
MRI and magnetization transfer imaging changes in the brain and cervical cord of patients with Devic's neuromyelitis optica.
OBJECTIVES: To assess MRI and magnetization transfer (MT) imaging changes in the brain and cervical cord from patients with Devic's neuromyelitis optica (DNO), and to compare them with those from patients with MS. BACKGROUND: In MS, MT imaging detects changes within the normal-appearing brain tissue (NABT). MS lesions in the cord usually are isointense on T1-weighted images. No study has investigated these two aspects in patients with DNO. METHODS: The authors obtained dual echo, fast fluid-attenuated inversion recovery, T1-weighted, and MT scans of the brain from 8 DNO patients, 10 MS patients, and 9 healthy volunteers. T2-weighted, short-tau inversion recovery, T1-weighted, and MT scans of the cervical cord also were obtained. The authors identified lesions visible on the different scans and quantified the volumes for those in the brain. MT ratio (MTR) histogram analysis of the NABT and of the entire cervical cord also was performed. RESULTS: No brain abnormalities were found on the T2-weighted scans from healthy volunteers and from seven DNO patients. No significant difference was found for any of the NABT-MTR histogram metrics between DNO patients and controls, whereas MS patients had a significantly lower histogram average MTR and peak height. No abnormalities were seen on any of the scans of the cervical cord from healthy volunteers. All DNO patients had a single lesion longer than two vertebral segments. Five of them were hypointense on T1-weighted scans. The authors identified 24 cord lesions from MS patients: 22 were shorter than two vertebral segments and none was hypointense. There was no difference in cervical cord MTR histogram metrics between DNO and MS patients. CONCLUSIONS: This study demonstrates that patients with Devic's neuromyelitis optica (DNO) and MS have different imaging characteristics of the brain and cervical cord. This provides further evidence that DNO is a clinical entity separate from MS.
Adult↗
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↗
Magnetization transfer imaging of patients with definite MS and negative conventional MRI.
OBJECTIVE: To assess, in a group of patients with clinically or laboratory-supported definite MS and negative conventional MRI scans of the brain, whether magnetization transfer imaging (MTI) is able to detect subtle white matter changes. BACKGROUND: MTI of the brain in patients with MS frequently demonstrates the presence of microscopic damage to white matter, which appears normal on conventional MRI. METHODS: Brain MRI and MTI scans were obtained from 11 patients with negative conventional MRIs of the brain, selected from 618 clinically or laboratory-supported definite MS cases scanned in the last 2 years in three Italian MS centers. RESULTS: Compared with control subjects, patients had significantly lower mean MT ratios (MTR) in the pons, cerebellum, and periventricular regions. The percentages of pixels with MTR values below 1, 2, and 3 SD of the mean MTR value of the control subjects were 7.6% (range, 3.2% to 11.8%), 5.2% (range, 2.0% to 8.5%), and 3.6% (range, 1.2% to 6.1%), respectively. They were mainly located in the white matter of the centra semiovalia, and usually were isolated. CONCLUSIONS: MTI can detect white matter abnormalities in patients with MS and negative conventional brain MRI scans. The detection of such abnormalities may increase diagnostic confidence in those cases where MS is clinically suspected, but conventional MRI does not suggest the diagnosis.
Adolescent↗
Long-term follow-up of isolated optic neuritis: the risk of developing multiple sclerosis, its outcome, and the prognostic role of paraclinical tests.
We evaluated the risk of developing clinically definite multiple sclerosis (CDMS) after an acute attack of isolated optic neuritis (ON) in 112 patients, in relation to demographic and paraclinical findings. Patients were examined by brain MRI, CSF analysis, and multiple evoked potentials (EPs); 10 were lost to follow-up, and the other 102 were enrolled in a prospective study (follow-up duration 6. 3 +/- 2.2 years). Of these, 37 (36.3%) developed CDMS after a mean interval of 2.3 +/- 1.6 years. The risk of developing CDMS was 13% after 2 years, 30% after 4, 37% after 6, and 42% after 8 and 10 years. Gender, age, and season of ON onset did not affect the risk. MS occurred in 37 of 71 patients (52.1%) with one MRI lesion or more; no patient with a normal MRI developed the disease. MS developed more frequently in patients with intrathecal IgG synthesis than in those without (43% vs. 28%), but the difference was not statistically significant. Multiple EPs showed a slight predictive value only including somatosensory EPs of the lower limb. Multiple sclerosis was mild in most cases (EDSS 2.2 +/- 1.9). The EDSS was less than 4 in 32 cases (86%), between 4 and 6 in 2 (5%), higher than 6.5 in 3 (8%).
Adult↗
Seat-belt-related injuries to the supra-aortic arteries.
Five seat-belt-related injuries occurring in four adults are reported. One injury involved the common carotid artery, two the internal carotid and two the subclavian arteries. Three of the four injured persons were asymptomatic and one had delayed-onset symptoms; none suffered stroke. There was no operative mortality or morbidity. Overall, the functional results of arterial reconstruction were good, with satisfactory patency at follow-up averaging 15 months.
Adult↗
Maternal inheritance of manic depression in hemizygotes for the G6PD-Mediterranean mutation. Indirect evidence for Xq28 transmission in Sardinia.
Both X-linkage and a parent-of-origin effect have been hypothesized in manic-depressive disorder. We have previously shown an allelic association between X-linked G6PD deficiency and manic depression in Mediterranean populations. To test both X-linkage and a parent-of-origin effect in manic depression further, we have studied 274 Sardinian manic-depressive probands and their parents. Excess of maternal transmission (P = 0.005) of major affective disorder was found in male probands carrying the G6PD-Mediterranean mutation. Our results provide indirect molecular support for an association between manic depression and the Xq28 chromosome region in Sardinia. Further studies on Xq28 using tests of allelic association and transmission disequilibrium with multiple DNA markers are required, to clarify the nature of the association we have found. Our study cannot implicate or exclude a direct role for G6PD deficiency in the aetiology of manic depression.
Adult↗
Interferon beta treatment for multiple sclerosis has a graduated effect on MRI enhancing lesions according to their size and pathology.
OBJECTIVE: The ability of recombinant human interferon beta-1a (rh-IFN beta-1a) to suppress multiple sclerosis activity, evaluated from MRI, was assessed across a range of lesions enhancing at different gadolinium-DTPA (Gd) doses and with different sizes. METHODS: Every 4 weeks, standard dose (Sd; 0.1 mmol/kg Gd) and triple dose (Td; 0.3 mmol/kgGd) MRI were obtained from 18 patients with relapsing-remitting multiple sclerosis for 3 months before and 4 months after starting treatment with 44 microgram rh-IFN beta-1a subcutaneously, once a week. RESULTS: The total numbers of enhancing lesions were 145 and 126 on Sd scans and 278 and 192 on the Td scans obtained before and after treatment. The introduction of treatment decreased, on average, the rate of appearance of new enhancing lesions seen on Sd and Td scans by 37% (p<0.001). Treatment effects on new enhancing lesions seen on Td scans was, on average, 28% higher than on those seen on Sd scans. The distribution of lesion sizes on Td scans changed significantly during the treatment period (p=0.05), due to a marked decrease in the number of small lesions. CONCLUSIONS: The effect of 44 microgram rh-IFN beta-1a in reducing multiple sclerosis disease activity, as monitored by Gd enhanced MRI, is not homogeneous, but graduated according to the pathological characteristics and size of the lesions.
Adult↗
Peripheral levels of caspase-1 mRNA correlate with disease activity in patients with multiple sclerosis; a preliminary study.
The cysteine protease caspase-1 plays a crucial part in the inflammatory process due to its ability to proteolitically activate proinflammatory cytokine precursors, such as interleukin (IL)-1beta and IL-18. Multiple sclerosis is a chronic inflammatory demyelinating disease of the CNS in which the pathogenic process is mainly orchestrated by proinflammatory cytokines. The role of caspase-1 in multiple sclerosis was evaluated by measuring its mRNA levels in peripheral blood mononuclear cells (PBMCs) from seven patients with relapsing-remitting multiple sclerosis every 15 days over a 1 year period. The recorded levels were compared with clinical and MRI evidence of disease activity. Brain MRI was performed monthly in each patient. Caspase-1 mRNA levels were significantly increased in PBMCs from patients with multiple sclerosis compared with healthy controls (p<0.001). In patients with multiple sclerosis, a twofold to threefold increase of caspase-1 mRNA mean level was found in the week preceding an acute attack (p<0. 05). The magnitude of caspase-1 mRNA increase correlated with the number of new (p=0.01) but not persisting gadolinium enhancing brain MRI lesions. In conclusion, caspase-1 might be involved in the immune mediated process underlying CNS inflammation and might represent a suitable peripheral immunological marker of disease activity in multiple sclerosis.
Adult↗
Measuring evoked responses in multiple sclerosis.
Evoked potentials (EPs) have been widely utilised in Multiple Sclerosis (MS) patients to demonstrate the involvement of sensory and motor pathways. Their diagnostic value is based on the ability to reveal clinically silent lesions and to objectivate the central nervous system damage in patients who complain frequently of vague and indefinite disturbances which frequently occurs in the early phases of the disease. The advent of magnetic resonance imaging (MRI) techniques has greatly reduced the clinical utilisation of EPs, which is not fully justifiable, as the information provided by EPs are quite different from those provided by MRI. The abnormalities of evoked responses reflect the global damage of the evoked nervous pathway and are significantly correlated with the clinical findings, while the vast majority of MRI lesions are not associated to symptoms and signs. Transversal and longitudinal studies have demonstrated that EP changes in MS are more strictly related to disability than MRI lesion burden. On the contrary, MRI is more sensitive than EPs in revealing the disease activity. Evoked responses modifications observed in MS are not disease-specific; moreover longitudinal studies showed latency and morphology changes of evoked responses not always related to clinical changes. Such a dissociation can be explained both by technical factors and by subclinical disease activity. To reduce the negative impact of technical aspects, only reproducible parameters of the evoked responses should be used to monitor disease evolution and therapeutic interventions.
Brain↗
Results of distal revascularization in elderly patients for critical ischemia of the lower limbs.
Thirty eight patients over 75 years of age were operated upon of 40 distal arterial revascularizations for critical ischaemia of the lower limbs. Arterial reconstruction was proposed to ambulatory, self sufficient patients, with a patent artery of the leg or the foot in continuity with pedal arch, at arteriography. The revascularized artery was the peroneal in 14 cases, the anterior tibial in 11, the posterior tibial in 9, the dorsalis pedis in 5, and the external plantar artery in 1 case. Postoperative mortality was 2.6%. No postoperative arterial occlusion occurred and no postoperative amputation needed to be performed. The mean follow-up of 37 patients surviving operation was 21 months (ext. 2-52 months). At 36 months interval, patients' survival was 43%, primary patency rate was 57%, and limb salvage rate was 76%, at life-table analysis. Distal revascularization enables a good number of elderly patients in critical ischaemia of the lower limb, to enjoy an active, independent life, with a viable limb.
Aged↗
Evoked potentials in diagnosis and monitoring of multiple sclerosis.
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Evoked Potentials, Motor↗
Can evoked potentials be useful in monitoring multiple sclerosis evolution?
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Disease Progression↗
Electrophysiological investigations in multiple sclerosis dementia.
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Cognition Disorders↗
Occurrence of thyroid autoimmunity in relapsing remitting multiple sclerosis patients undergoing interferon-beta treatment.
We analyzed the titer of antithyroid autoantibodies (Abs) and thyroid function in 17 multiple sclerosis (MS) patients undergoing interferon-beta (IFN-beta) treatment and in 40 MS control patients. Basal evaluation revealed normal thyroid function in all patients. Abs were detected in 5 IFN-beta-treated patients (29%) and in 4 MS control patients (10%). Our results indicate that IFN-beta treatment may lead to thyroid autoimmunity. We therefore recommend periodic evaluations of antithyroid Abs and thyroid functionality in IFN-beta-treated MS patients.
Adjuvants, Immunologic↗
Results of bypasses to the anterior tibial artery through the interosseous membrane.
The purpose of the present study was to retrospectively evaluate the results of anatomically tunneled grafts to the anterior tibial artery for distal revascularization in terms of patency and limb salvage rates as well as local morbidity, which can lengthen the postoperative hospital stay. Twenty-three patients received 24 bypasses to the anterior tibial artery, with grafts tunneled through the interosseous membrane. The mean age was 67 years; 10 patients were diabetic, 12 were smokers, 9 presented with significant coronary artery disease, and 2 with chronic renal insufficiency. The donor vessel was the common femoral artery in 17 cases, the superficial femoral artery in 4, and the infra-articular popliteal artery in 3. The graft material consisted in the reversed saphenous vein in 4 cases, the non-reversed devalvulated ex situ saphenous vein in 11, composite polytetrafluoroethylene (PTFE) + inversed saphenous vein in 6, and PTFE alone in 3 cases. No postoperative mortality was observed, nor was there postoperative graft occlusion or need for major amputation. The average postoperative length of stay in the hospital was 9.7 days. Two local surgical wound complications were observed, which did not necessitate a postoperative hospital stay exceeding 15 days. Cumulative primary patency and limb salvage rates at 3 years were 50% and 70%, respectively. Anatomic tunneling of grafts to the anterior tibial artery yields patency and limb salvage rates comparable to those reported in the literature for distal bypasses and, considered overall, an acceptably low local morbidity and short hospital stay. Definitive superiority over externally tunneled grafts, however, is not definitely demonstrated by this study and should be prospectively tested.
Aged↗