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Biomedical subjects

D Caputo

Publications and source records attributed to D Caputo.

At least 19 recordsLinked to original sources

Diffusion anisotropy of the cervical cord is strictly associated with disability in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with severe cervical cord damage due to degeneration of the corticospinal tracts and loss of lower motor neurones. Diffusion tensor magnetic resonance imaging (DT MRI) allows the measurement of quantities reflecting the size (such as mean diffusivity) and orientation (such as fractional anisotropy) of water-filled spaces in biological tissues. METHODS: Mean diffusivity and fractional anisotropy histograms from the cervical cord of patients with ALS were obtained to: (1) quantify the extent of tissue damage in this critical central nervous system region; and (2) investigate the magnitude of the correlation of cervical cord DT MRI metrics with patients' disability and tissue damage along the brain portion of the corticospinal tracts. Cervical cord and brain DT MRI scans were obtained from 28 patients with ALS and 20 age-matched and sex-matched controls. Cord mean diffusivity and fractional anisotropy histograms were produced and the cord cross-sectional area was measured. Average mean diffusivity and fractional anisotropy along the brain portion of the corticospinal tracts were also measured. RESULTS: Compared with controls, patients with ALS had significantly lower mean fractional anisotropy (p = 0.002) and cord cross-sectional area (p<0.001). Mean diffusivity histogram-derived metrics did not differ between the two groups. A strong correlation was found between mean cord fractional anisotropy and the ALS Functional Rating Score (r = 0.74, p<0.001). Mean cord and brain fractional anisotropy values correlated moderately (r = 0.37, p = 0.05). CONCLUSIONS: Cervical cord DT MRI in patients with ALS allows the extent of cord damage to be graded. The conventional and DT MRI changes found are compatible with the presence of neuroaxonal loss and reactive gliosis, with a heterogeneous distribution of the pathological process between the brain and the cord. The correlation found between cord fractional anisotropy and disability suggests that DT MRI may be a useful adjunctive tool to monitor the evolution of ALS.

Adult↗

Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years.

Reliable prognostic markers of primary progressive (PP) multiple sclerosis evolution are still needed. Diffusion tensor (DT) MRI can quantify normal-appearing white matter (NAWM) and grey matter (GM) damage in multiple sclerosis patients. We investigated whether conventional and DT-MRI-derived measures can predict the long-term clinical evolution of PP multiple sclerosis. In 54 PP multiple sclerosis patients, conventional and DT-MRI scans of the brain and T1-weighted scans of the cervical cord were acquired at baseline and after a median follow-up of 15 months. Another clinical evaluation was performed, 56 months after baseline, in 52 patients. Measures of lesion load, brain and cord atrophy were obtained. Histograms of the mean diffusivity (MD) and fractional anisotropy (FA) values from the NAWM and GM were analysed. At follow-up, 35 patients (65%) experienced a confirmed disability progression. Baseline expanded disability status scale score and average GM MD were independent predictors of subsequent clinical deterioration in a multivariable model (Nagelkerke R2: 0.44; discriminating ability: 81%). A lower level of disability and a more severe GM damage identify PP multiple sclerosis patients with an increased risk of disease progression over the subsequent 5 years. These data may be relevant to select patients for future exploratory phase II trials.

Adult↗

Extracorporeal photochemotherapy: a safety and tolerability pilot study with preliminary efficacy results in refractory relapsing-remitting multiple sclerosis.

Extracorporeal photochemotherapy (ECP) is an immunomodulating procedure consisting of autologous reinfusion of peripheral blood mononuclear cells (PBMC) after direct exposure to 8-methoxy-psoralen and UV-A. It has been described as a successful treatment for different T-cell-mediated diseases and preliminary results suggest that ECP might be effective in the treatment of relapsing-remitting multiple sclerosis, but does not significantly alter the course of the progressive form of MS. In this study, we report the safety data and some preliminary efficacy evidence obtained using ECP in the treatment of five patients with refractory relapsing-remitting (RR) MS: in most cases ECP induced a reduction in the relapse rate and an EDSS stabilisation, with an apparent general MRI stabilisation. In conclusion, our results confirm ECP safety and tolerability and suggest that this treatment might be useful as a therapeutic alternative in the subgroup of RRMS patients not responsive to or not eligible for traditional immunomodulating or immunosuppressive treatments.

Adult↗

Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study.

BACKGROUND: Magnetization transfer ratio (MTR) permits the quantitative estimation of cervical cord tissue damage in patients with multiple sclerosis (MS). OBJECTIVE: To determine whether a single time-point MTR scan of the cervical cord is associated with short-term disease evolution in patients with relapsing-remitting (RR) MS. METHODS: Using a 1.5-T magnetic resonance imaging (MRI) system with a tailored cervical cord phased array coil, fast short-tau inversion recovery (fast-STIR) and MTR scans were obtained from 14 untreated patients with RRMS at baseline. Cervical cord MTR histograms were derived. Over the 18-month follow-up period, relapse rate was measured and disability assessed by the Expanded Disability Status Scale (EDSS) score. RESULTS: Average cervical cord MTR was correlated with relapse rate (r= -0.56, P=0.037). A moderate correlation (r values ranging from -0.33 to -0.36) between baseline cervical cord MTR metrics and EDSS changes over 18 months was also noted, albeit statistical significance was not reached (P = 0.26 and 0.21, respectively) perhaps because of the relatively small sample size. CONCLUSIONS: This study suggests that a 'snapshot' MT MRI assessment of the cervical cord may detect cervical cord tissue changes associated with short-term disease evolution in RRMS.

Adult↗

Antimicrobial susceptibility, biochemical and genetic profiles of Staphylococcus haemolyticus strains isolated from the bloodstream of patients hospitalized in critical care units.

Staphylococcus haemolyticus strains (n=20), responsible of blood stream infections, were consecutively isolated from patients hospitalized in two different wards at high risk of infection. Strains displayed high rate of resistance to oxacillin (90%). All strains but two with decreased susceptibility (MIC = 4 microg/mL), were sensitive to vancomycin. Ten strains were resistant to teicoplanin. Among the strains susceptible to glycopeptides, three displayed heteroresistance to vancomycin and seven to teicoplanin, when tested by Etest technique with 2 x McFarland inoculum. Biochemical reactions allowed to assign strains to eight biotypes, with 11 strains clustering under two main biotype A and biotype B. Pulsed-field-gel-electrophoresis (PFGE) identified 11 different PFGE-types. Seven strains grouping under the major PFGE-type 1 and three strains clustering in PFGE-type 2, closely correlated to biotype A and biotype B respectively. Seven teicoplanin-resistant isolates clustered in the PFGE-type 1, two in the PFGE-type 2 and one in PFGE-type 5. Therefore, teicoplanin-resistant strains were biochemically and genetically related and clonally distributed, despite different clones of S. haemolyticus circulated in the units during the study period.

Adult↗

Can anal manometry predict anal incontinence after fistulectomy in males?

BACKGROUND: Disordered continence is frequently reported after operations for anal fistulae and pre-operative anorectal physiology may be carried out prior to surgery to improve functional outcome. Elderly patients and multiparous females are at higher risk for incontinence, whereas males under 60 have stronger sphincters. The aim of this study was to investigate the predictive role of anal manometry and the causes of postoperative soiling and its effect on the quality of life in males with intact sphincters undergoing excision of either trans or supra sphincteric fistulae. METHODS: Thirty-eight patients (median age 47 years) were analysed retrospectively. None had previous anal surgery and all were fully continent. Five had Crohn's disease. Anal pressures and rectal sensation were evaluated prior to fistulectomy by means of anal manometry in all cases and after surgery in those who had postoperative incontinence. A cutting seton was used in 17 patients, a rectal advancement flap in 15 and a double rectal-cutaneous flap in six. None had a lay-open. The intersphincteric plane was explored and drained in all cases. A previously described incontinence grading and score was used to assess postoperative soiling. The median follow-up was 22 (range 5-89) months. The patients with postoperative anal incontinence were evaluated with the Gastrointestinal quality of Life Index Questionnaire (0:poor, 4:good) at a median follow-up of 49 months. RESULTS: Twenty-nine (76%) patients were continent after surgery, whereas 9 (24%) complained of some degree of anal incontinence (minor in 4, severe in 1, the 1-6 incontinence score being 3.7 +/- 1.3 (mean +/- s.d.m.). Their Quality of life score was 3.8 +/- 0.5 (mean +/- sdm). None of them had Crohn's disease, five had frequent diarrhoea, four had a reintervention for either anal fissure or recurrent fistula (two), three had a postseton anal deformity. No difference was found between continent and incontinent patients as far as pre-operative anal pressures were concerned, but the maximum rectal volume threshold was significantly higher in incontinent patients, 165 +/- 67 vs. 123 +/- 49 ml of air (P = 0.04). CONCLUSIONS: Sphincter division, diarrhoea and anal deformity may cause soiling after fistulectomy in males and it does not severely affect quality of life. Surgery rather than manometry may predict it and rectal sensation may play a role which needs further investigation.

Adult↗

Vestibular evoked myogenic potentials in multiple sclerosis: clinical and imaging correlations.

Patients with multiple sclerosis (MS) frequently report symptoms related to vestibular disorders in the course of their disease. At present, the fundamental tests assessing vestibulospinal involvement are posturography and vestibular evoked myogenic potentials (VEMPs). While posturography cannot be performed in every subject requiring minimal stance control, VEMPs do not require any specific skill on the part of the subjects and they may be investigated in all patients able to sit. VEMPs were recorded for 40 patients (17 men, 23 women; mean age 38 years, range 17-71 years) fulfilling diagnostic criteria of clinically defined MS, by means of rarefaction clicks, recording modulation of sterno-cleido-mastoideus tonic contraction saccule-mediated modulation. VEMPs were found to be abnormal in 28 of 40 patients. In 18 of the cases the VEMPs were asymmetric, i.e., had a prolonged latency on one side. In six cases latency was increased on both sides (mean delay 4.1 ms). In four subjects VEMPs were absent on one side. Concordance with clinical findings of presence/absence of brainstem involvement was found in 55% and with MRI findings in 65% of the cases. Abnormal VEMPs indicated brainstem dysfunction in four patients (10%) with normal MRI and no specific clinical signs.

Adolescent↗

Myelin basic protein gene is associated with MS in DR4- and DR5-positive Italians and Russians.

BACKGROUND: The myelin basic protein (MBP) gene may confer genetic susceptibility to multiple sclerosis (MS). The association of MS with alleles of the (TGGA)n variable number tandem repeat (VNTR) 5' to the MBP gene is the subject of conflicting reports. OBJECTIVE: To study possible MS association with VNTR alleles of MBP gene in ethnic Italians and ethnic Russians. METHODS: Two hundred sixty-nine unrelated patients with definite MS and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the MBP VNTR region and for the human leukocyte antigen (HLA) class II DRB1 gene. The phenotype, allele, and genotype frequencies for two groups of MBP alleles were determined. Patients and control subjects were stratified according to HLA-DRB1 phenotypes. RESULTS: The distribution of MBP alleles and genotypes in the two ethnic groups, including both MS patients and control subjects, was very similar. When MS patients and healthy control subjects were stratified according to HLA-DRB1 phenotypes, a significant association of MS with MBP alleles was found only in the DR4- and DR5-positive subgroups. A significant association with MBP alleles was also observed in the nonstratified groups, owing mainly to the contribution of the DR4- and DR5-positive individuals. CONCLUSION: Polymorphism of the MBP or another gene in its vicinity appears to contribute to the etiology of MS for the subgroups of DR4- and DR5-positive Italians and Russians.

Adolescent↗

A post-marketing study on interferon beta 1b and 1a treatment in relapsing-remitting multiple sclerosis: different response in drop-outs and treated patients.

BACKGROUND: Interferon beta 1b (Betaferon) and 1a (Avonex) were licensed in Italy for treating relapsing-remitting multiple sclerosis in February 1996 and August 1997, respectively. OBJECTIVES: To evaluate the effectiveness of these agents on the basis of clinical experience in northern Italian multiple sclerosis centres. DESIGN: Clinical data on patients with relapsing-remitting multiple sclerosis were collected on an appropriate form from 65 centres in northern Italy. Intention to treat analysis was not possible, so patients who discontinued treatment (drop-outs) and who continued treatment (treated) were analysed separately. The main outcome measures were annual relapse frequency, number of relapse-free patients, mean change in extended disability status scale score (EDSS), and number of patients who worsened. RESULTS: 1481 patients were included; 834 were treated with Betaferon and 647 with Avonex for mean periods of 21.4 and 12.0 months, respectively. Basal EDSS was 2.37 and 2.17, respectively, and relapse frequency was 1.62 and 1.45. The annual relapse rate decreased by more than 60% with Betaferon and 55% with Avonex. The proportions of relapse-free, improved, and worsened patients were similar in the two groups. More patients interrupted treatment with Betaferon (41.1%) than with Avonex (15.3%); such patients showed more active disease at baseline and during treatment. The incidence of side effects was higher in Betaferon treated patients. CONCLUSIONS: The effectiveness of Betaferon and Avonex is confirmed. There was a more marked effect than expected from the experimental trial results. This might reflect differences in inclusion criteria, or, more likely, loss of drop-outs, favouring selective retention of responders.

Adjuvants, Immunologic↗

Evidence for widespread movement-associated functional MRI changes in patients with PPMS.

BACKGROUND: Previous work has suggested that functional reorganization of cortical motor areas might have a role in limiting the motor deficits in patients with MS. OBJECTIVE: To test whether movement-associated cortical changes in MS might extend beyond the "classic" motor areas and involve sites for multimodal integration. METHODS: fMRI was used to assess patterns of brain activations associated with 3 different motor tasks in 30 right-handed patients with primary progressive MS (PPMS) and variable degrees of motor impairment, which were compared with those from 15 right-handed, sex- and age-matched control subjects. RESULTS: Compared with control subjects, patients with MS showed increased activation of brain regions within both traditional motor planning and execution regions (including the supplementary motor area and the cingulate motor area), the insula (a region implicated in sensory processing), and several multimodal cortical regions in the temporal, parietal, and occipital lobes. In patients, the extent of the fMRI activations was strongly correlated with MR lesion burden (r ranging from 0.70 to 0.86, p < 0.001). CONCLUSIONS: This study shows that movement-associated cortical activation in patients with PPMS is widely distributed and also involves multimodal "nonmotor" cortical networks. It also suggests that adaptive cortical reorganization might be one of the mechanisms limiting the clinical impact of MS in the progressive phases of the disease.

Adult↗

Correlations between structural CNS damage and functional MRI changes in primary progressive MS.

In patients with primary progressive multiple sclerosis (PPMS), we investigated whether brain and cervical cord structural changes in lesions and normal-appearing brain tissue (NABT), measured using conventional, magnetization transfer (MT), and diffusion tensor (DT) MRI, are correlated with movement-associated cortical activations measured using functional magnetic resonance imaging (fMRI). From 26 right-handed PPMS patients and 15 right-handed, sex- and age-matched healthy controls, we obtained: (a) brain and cervical cord dual-echo scans and MT ratio (MTR) maps; (b) brain mean diffusivity (D(-)) maps, and (c) f-MRI (flexion-extension of the last four fingers of the right hand). All PPMS patients had no previous symptoms affecting their right upper limbs, which were functionally normal. Healthy volunteers showed more significant activation in the ipsilateral cerebellar hemisphere than PPMS patients. PPMS patients showed greater activation bilaterally in the superior temporal gyrus, ipsilaterally in the middle frontal gyrus, and, contralaterally in the insula/claustrum. In PPMS patients, moderate to strong correlations (r values ranging from 0.59 to 0.68) were found between relative activations of cortical areas located in a widespread network for sensory-motor and multimodal integration and the severity of structural changes of the NABT (as measured using MT and DT MRI) and the severity of cervical cord damage (as measured using MT MRI). This study shows that the pattern of cortical activation of PPMS patients is different from that of normal controls even when performing a motor task with clinically unaffected limbs. It also suggests that cortical reorganization might be able to limit the consequences of MS injury in the brain and cervical cord.

Adult↗

Sacral nerve neuromodulation improves physical, psychological and social quality of life in patients with fecal incontinence.

There are several therapeutic options for fecal incontinence but often they do not achieve good results in the long run. This study dealt with sacral nerve modulation, a new therapeutic option. Twenty-one patients underwent pudendal nerve evaluation (PNE) at our institution. Nine patients were affected by both fecal and urinary incontinence, 3 had fecal incontinence and anal pain, 5 had fecal incontinence and pelvic floor dyssynergia, and 4 had isolated fecal incontinence. They underwent morphological, functional and psychological tests prior to PNE, showing no sphincter rupture, almost normal anal pressures, impaired rectal sensation and deficient psychological pattern. All patients underwent at least two nerve evaluations. Four of 21 patients (19%) were selected to receive a permanent sacral electrode, as PNE seemed to have improved their symptoms by >75%. A median follow-up of 15 months (range, 6-24 months) showed that this method decreases weekly episodes of incontinence and increases maximal squeeze pressure. We demonstrated an increase in basal pressure in 3 of 4 patients (all with isolated fecal incontinence). Rectal sensation threshold decreased in three patients; urge threshold decreased in two patients and increased in two patients, but in each patient we got a stabilization. We evaluated the quality of life by applying the Short Form Health Survey test (SF-36). All 4 patients showed a significant increase in the scores of physical, emotional and social role functioning after the permanent implant. In conclusion, sacral nerve modulation may improve physical, physiological and social quality of life in selected groups of incontinent patients without gross sphincter lesions and with impaired rectal sensation.

Adult↗

Single-cell analysis of cytokine production shows different immune profiles in multiple sclerosis patients with active or quiescent disease.

Peripheral blood mononuclear cells of multiple sclerosis (MS) patients were stimulated with myelin basic protein (MBP) together with anti-CD28 monoclonal antibody and staphylococcal enterotoxin B to optimize cytokine production by antigen-specific cells. Type 1 (IL-2, IL-12, IFNgamma) and pro-inflammatory (TNFalpha, IL-1beta, IL-6) cytokines were augmented in CD4+, CD8+, and CD14+ cells of acute MS patients and of patients undergoing disease reactivation. These cytokines were reduced in IFNbeta-treated and in stable MS patients; type 2 cytokines (IL-4, IL-10) were increased in these patients. Similar immune profiles are seen in MS patients in whom remission is naturally or pharmacologically (IFNbeta) achieved. Cytokine alterations are particularly evident in CD14+ cells, underlying their critical role in the modulation of the immune response.

Adjuvants, Immunologic↗

Vertigo and multiple sclerosis: aspects of differential diagnosis.

Equilibrium disorders caused by involvement of brainstem and cerebellar structures are common in patients with multiple sclerosis (MS), but peripheral conditions such as benign paroxysmal positional vertigo (BPPV) can be sometimes confused with those of a central origin. Therefore, an accurate otoneurologic investigation paying attention to differential diagnosis aspects should be performed in these subjects. Among available diagnostic tools, electro-oculography, posturography and vestibular evoked myogenic potentials (VEMPs) are especially suited to assess vestibulo-oculomotor and vestibulospinal systems. This paper briefly describes the most recent otoneurologic diagnostic strategies for MS patients and the results of initial clinical experiences, and finally provides suggestions for differentiating MS-related vestibular disorders from other common otoneurological conditions.

Ataxia↗

In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis.

In patients with primary progressive (PP) multiple sclerosis, brain MRI lesion activity and burden are low, despite the presence of severe neurological impairment. On the contrary, the degree of cord atrophy and diffuse tissue damage in the brain and cervical cord have been found to be associated with clinical disability. Against this background, this study aimed at providing an in vivo indirect assessment of brain and cervical cord pathology in a large cohort of PP multiple sclerosis patients, using conventional MRI and magnetization transfer imaging (MTI). Ninety-one PP multiple sclerosis patients, 36 secondary progressive (SP) multiple sclerosis patients and 30 healthy controls underwent brain and cervical cord MRI scans, using dual echo (brain) or fast short-tau inversion recovery (cervical cord) MTI and T(1)-weighted sequences. For the brain, T(2) hyperintense and T(1) hypointense lesion volumes were calculated and the volume of the whole of the brain tissue measured. For the cervical cord, the number and burden of lesions and the cross-sectional area were assessed. MTI scans were post-processed and analysed to obtain magnetization transfer ratio (MTR) histograms from the whole of the brain and cervical cord tissue and from the normal-appearing brain tissue in isolation. In PP multiple sclerosis patients, brain, normal-appearing brain tissue and cervical cord MTR histogram-derived metrics revealed the presence of diffuse tissue damage whose characteristics did not significantly differ from those of SP multiple sclerosis patients, even though SP multiple sclerosis patients had higher MRI-visible lesion burdens. None of the correlations between MRI or MTI measures obtained from the brain and the cord were significant. PP multiple sclerosis patients' disability was significantly, albeit weakly associated with a composite MR model including measures of loss and intrinsic damage of cervical cord tissue. Our data indicate the presence of a diffuse tissue damage undetectable by conventional MRI in PP multiple sclerosis patients, whose extent seems to match that of SP multiple sclerosis patients with similar levels of disability. They also suggest that the severity of multiple sclerosis pathology in the cervical cord is one of the factors contributing to neurological impairment in PP multiple sclerosis.

Adult↗

A polymorphism in the repetitive (TGGA)n sequence 5' to the human myelin basic protein gene in Italian multiple sclerosis patients.

Human myelin basic protein (hMBP) gene is one of the candidate genes in the complex mosaic of multiple sclerosis (MS) susceptibility. In this study we verified the distribution of the polymorphism of the region 5' flanking the first exon of the hMBP gene, in 97 relapsing remitting, 74 primary progressive Italian MS patients, and in 236 healthy controls, using polymerase chain reaction (PCR) and gel electrophoresis analysis in this region from 1116 - 1540 nt. Three different band patterns were observed: one homozygote with a 354 bp long fragment, one homozygote with 424 bp long fragment and one heterozygote with both bands present. The short fragment was statistically more frequent in RRMS patients than in HC (P<0.05). The long fragment was more present in HC. Similarly the short homozygous pattern (354 bp/354 bp) was significantly higher in the RRMS patients versus the healthy controls (P<0.01). The sequence analysis of the hMBP alleles showed that while the long fragments matched the prototype sequence completely, all the short fragments showed a deletion of 70 bp from nt 1177 to nt 1247, which explains the short 354 bp allele detected by PCR. Moreover two single mismatches in positions 1386 (T-->C) and 1431 (G-->A), were present only in the short hMBP fragment.

Alleles↗