Biomedical subjects

R Capra

Publications and source records attributed to R Capra.

At least 19 recordsLinked to original sources

PubMed2006

Grading cervical cord damage in neuromyelitis optica and MS by diffusion tensor MRI.

The authors assessed the ability of diffusion tensor MRI to grade cervical cord damage in 10 patients with neuromyelitis optica, 10 patients with multiple sclerosis, and 10 healthy controls. The three groups differed in terms of average mean diffusivity (p = 0.008) and average fractional anisotropy (p = 0.04). There was a correlation between the Expanded Standard Disability Status Scale score and cord average mean diffusivity (r = 0.52, p = 0.02).

Adult↗

PubMed2006

MR imaging assessment of brain and cervical cord damage in patients with neuroborreliosis.

BACKGROUND AND PURPOSE: Neuroborreliosis is frequently indistinguishable from multiple sclerosis (MS) on both clinical and radiologic grounds. By using MR imaging, we assessed "occult" brain white matter (WM), brain gray matter (GM), and cervical cord damage in patients with neuroborreliosis in an attempt to achieve a more accurate picture of tissue damage in these patients, which might contribute to the diagnostic work-up. METHODS: We studied 20 patients with neuroborreliosis and 11 sex- and age-matched control subjects. In all subjects, we acquired dual echo, T1-weighted, diffusion tensor (DT) and magnetization transfer (MT) MR imaging scans of the brain and fast short-tau inversion recovery and MT MR imaging scans of the cervical cord. T2-visible lesion load was measured by using a local thresholding segmentation technique. Mean diffusivity and fractional anisotropy histograms of the brain and cervical cord MT ratio histograms were produced. Normalized brain volumes (NBV) were measured by using SIENAx. RESULTS: Brain T2-visible lesions were detected in 12 patients, whereas no occult damage in the normal-appearing WM and GM was disclosed by using MT and DT MR imaging. No macroscopic lesions were found in the cervical cord, which was also spared by occult pathology. NBV did not differ between patients with neuroborreliosis and control subjects. CONCLUSION: This study shows that, contrary to what happens in MS, occult brain tissue damage and cervical cord pathology are not frequent findings in patients with neuroborreliosis. These observations might be useful in the diagnostic work-up of patients with neuroborreliosis and T2 brain lesions undistinguishable from those of MS.

Adult↗

PubMed2005

Mitoxantrone for multiple sclerosis.

BACKGROUND: Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome measures of disease activity in multiple sclerosis (MS) patients. OBJECTIVES: The objective was to assess the efficacy and safety of MX in relapsing-remitting MS (RRMS), progressive relapsing MS (PRMS) and secondary progressive MS (SPMS). SEARCH STRATEGY: We searched the Cochrane MS Group Trials Register (searched April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004), MEDLINE (Pub Med) (January 1966 to April 2005), EMBASE (January 1974 to April 2005), and reference lists of articles. We also undertook hand searching and contacting trialists and pharmaceutical companies. SELECTION CRITERIA: The trials were selected if double-blinded, placebo-controlled, randomised, irrespective of eventual additive therapy (such as steroids). DATA COLLECTION AND ANALYSIS: Three reviewers independently selected articles for inclusion, assessed trials' quality and extracted data. MAIN RESULTS: Four trials involving 270 participants were included. MX was found to reduce the progression of disability at 2 years follow-up (proportion of participants with 6-months confirmed progression of disability: Odds Ratios (OR) 0.3, p = 0.05). Similar figures were found regarding the reduction in annualised relapse rate and the proportion of patients free from relapses at 1 and 2 years, as well as the number of patients with active MRI lesions at 6 months/ 1 year only. Side effects reported in the trials were more frequent in treated patients than in controls. Caution must be exercised in drawing conclusions from such data because of the heterogeneous quality and characteristics of the included trials, which are different in terms of treatment schedule and type of enrolled patients. More than half of the included patients came from a single study. Moreover, from the included trials, it was not possible to estimate the long-term efficacy and safety of MX, which may raise concerns about the risk of cardiotoxicity and therapy-related leukemias, which is increasingly reported in the literature. AUTHORS' CONCLUSIONS: MX is moderately effective in reducing the disease progression and the frequency of relapses in patients affected by RR, PR and SP MS in the short-term follow-up (2 years), even if the results are based on trials heterogeneous in terms of drug dosage and inclusion criteria. No major neoplastic or symptomatic cardiotoxicity related to MX have been reported from the trials. However, longer follow-up studies are highly warranted to better explore the efficacy and safety of the drug, mainly as regards the long-term risk of therapy-related leukemias and cardiotoxicity. As a conclusion, MX has a partial efficacy, but, due to its unclear long-term safety profile, it should be used to treat patients with worsening RR and SP MS with evidence of worsening disability.

Humans↗

PubMed2005

Early peripheral nerve abnormalities in impaired glucose tolerance.

Increased prevalence of impaired glucose tolerance (IGT) has been recently detected in patients with painful sensory neuropathy. To determine whether nerve abnormalities are present in IGT we investigated IGT subjects without clinical neuropathy. Nerve conduction studies (NCS) were performed in 12 subjects with IGT without symptoms and signs of neuropathy. The results were compared with those obtained from 12 patients with type 2 diabetes (DM) without clinical neuropathy and 12 healthy controls. Sensory NCS of the sural nerve were performed on different segments, the distal-leg (10 cm proximal to the lateral malleolus) and the proximal-leg segment (10 cm more proximal). The distal conduction velocity of the sural nerve was increased in IGT subjects, compared both to healthy controls and DM patients. No difference was found among the groups with respect to the sensory conduction velocity of the sural nerve fibers in the proximal-leg segment. A reduction of both distal and proximal amplitudes of the sural nerve action potentials was detected in DM patients compared with IGT subjects and controls. The abnormal conduction velocity in the distal segment of the sural nerve, observed in IGT subjects without clinical neuropathy, suggests that the myelin dysfunction of the distal sensory fibers represents the earliest detectable nerve response to the hyperglycemia. The reduced amplitude of the sural nerve action potential in asymptomatic patients with DM arises from the axonal degeneration and represents a more advanced stage of nerve disease.

Diabetic Neuropathies↗

PubMed2004

Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPA gene in Italian families.

Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurodegenerative disorder due to mutations in the alpha-tocopherol transfer protein (TTPA) gene on chromosome 8q13. AVED patients have progressive spinocerebellar symptoms and markedly reduced plasma levels of vitamin E. We studied neurological phenotype at diagnosis, and long-term effect of vitamin E supplementation in 16 patients from 12 Italian families. The most common mutations were the 744delA and 513insTT. Two novel TTPA mutations were identified: a severe truncating mutation (219insAT) in a homozygous patient, and a Gly246Arg missense mutation (G246R) in a compound heterozygous patient. The missense mutation was associated with a mild and slowly progressive form of the disease. Vitamin E supplementation therapy allowed a stabilization of the neurological conditions in most of the patients. However, development of spasticity and retinitis pigmentosa was noted in a few patients during therapy. Prompt genetic characterization of AVED patients may allow an effective early treatment and an adequate genetic counseling.

Adolescent↗

PubMed2004

Very low level laser therapy attenuates edema and pain in experimental models.

In this study, we tested a new square wave microprocessor-controlled red laser with an extremely low peak power output (<3 mW; very low level laser therapy [vLLLT]) in experimental pain in the rat. Acute inflammation was induced by intraplantar injection of carrageenan, chronic inflammation was induced by complete Freund's adjuvant (CFA) and neuropathic pain was produced by sciatic nerve chronic constriction injury (CCI). In our study vLLLT was effective in reducing edema and hyperalgesia in acute and chronic inflammation if administered at the points usually selected for acupuncture. Moreover, spontaneous pain and thermal hyperalgesia were reduced in CCI rats treated with vLLLT In conclusion, vLLLT reduced edema and induced analgesia in experimental plantar pain in rats. We interpret this to mean that enkephalin mRNA level was strongly upregulated in the external layers of the dorsal horn of the spinal cord in CFA and CCI animals, and that vLLLT further increased the mRNA level in single neurons.

Animals↗

PubMed2003

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↗

PubMed2001

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↗

PubMed2000

Cervical cord magnetic resonance imaging findings in systemic immune-mediated diseases.

Brain magnetic resonance imaging (MRI) findings in patients with systemic immune-mediated diseases (SID) affecting the central nervous system (CNS) are heterogeneous and lack diagnostic specificity. In the present study, we evaluated the potential role of cervical cord MRI for increasing confidence when making a diagnosis of SID. Sagittal, T2-weighted images of the cervical cord were obtained in patients affected by systemic lupus erythematosus (SLE) with (NSLE, n=9) and without clinical CNS involvement (n=15), Behçet disease (BD, n=5), Wegener granulomatosis (WG, n=9), antiphospholipid antibody syndrome (APLAS, n=6) and multiple sclerosis (MS, n=10). Spinal cord hyperintense lesions were found in 9/10 MS patients, while no lesions were visible in the cervical cord of any patient with SID, regardless of the presence or absence of brain abnormalities. Cervical cord MRI can be useful in diagnosing patients suspected of having a SID.

Adult↗

PubMed2000

The contribution of fast-FLAIR MRI for lesion detection in the brain of patients with systemic autoimmune diseases.

Fast fluid-attenuated inversion recovery (fFLAIR) is more sensitive that conventional or fast spin echo T2-weighted magnetic resonance imaging (MRI) for detecting lesions in the brain of patients with ischemic, inflammatory, or demyelinating diseases of the CNS. We investigated whether the use of fFLAIR also increases the sensitivity of brain MRI assessment in patients with systemic autoimmune disorders. Turbo spin echo (TSE) dual-echo and fFLAIR scans of the brain were obtained from patients affected by systemic lupus erythematosus (SLE) with (NSLE, n = 9) and without clinical CNS involvement (n = 15), Behçet disease (n = 5), Wegener granulomatosis (n = 9), and antiphospholipid antibody syndrome (n = 6). Brain hyperintense lesions were counted and classified according to their size and their location by two observers by consensual agreement. The total lesion volume was measured using a semiautomated technique for lesion segmentation on both TSE and fFLAIR scans. The imaging modalities showed brain hyperintense lesions in all 9 SLE patients with CNS involvement, 5 of 15 SLE patients without CNS involvement, 5 of 9 patients with Wegener granulomatosis, 1 of 5 with Behçet disease, and 3 of 6 with antiphospholipid antibody syndrome. A total of 342 lesions were seen on both sequences; 88 were seen only on TSE and 54 only on fFLAIR scans. The average number of brain lesions per scan was higher on TSE than on fFLAIR, since significantly more discrete (P<0.002) and small (P = 0.004) lesions were seen on TSE than on fFLAIR. The median total lesion volume, however, was similar on TSE and fFLAIR. Our study indicates that the use of fFLAIR does not improve the sensitivity of fast dual-echo MRI for detecting brain abnormalities in patients with systemic autoimmune disorders.

Adult↗

PubMed2000

A comparison of the sensitivity of MRI after double- and triple-dose Gd-DTPA for detecting enhancing lesions in multiple sclerosis.

We compared the number and volume of enhancing lesions detected in patients with multiple sclerosis (MS) seen on post-contrast T(1)-weighted scans obtained after the injection of different gadolinium-DTPA (Gd) doses. Enhanced magnetic resonance imaging (MRI) scans were obtained from 16 patients with relapsing remitting or secondary progressive MS on two different occasions separated by an interval of approximately 24 h. On the first occasion, enhanced scans were obtained 15 min after the injection of a double dose of Gd (0.2 mmol/Kg), on the second 15 min after the injection of a triple dose (0.3 mmol/Kg) of Gd. Scans were assessed by consensus in a random order by two observers unaware of the dose of Gd used. We counted the same 30 enhancing lesions on both double dose and triple dose scans from 9 patients. The mean (SD) volumes of enhancing lesions were 1.7 (2.7) mL on double dose and 1.9 (3.4) mL on triple-dose scans. This difference was not statistically significant. This study demonstrated that double dose of Gd has a sensitivity for detecting MS activity similar to that of a triple dose, with the advantage of a significant cost saving.

Adult↗

PubMed2000

Serial gadolinium-DTPA of spinal cord MRI in multiple sclerosis: triple vs. single dose.

We compared the sensitivity of single and triple dose Gd-DTPA magnetic resonance imaging (MRI) in detecting enhancing lesions in the spinal cord (SC) from 15 patients with multiple sclerosis (MS). The patients were examined monthly on four occasions. We detected two enhancing lesions in two of 15 (13%) patients when a single dose of Gd-DTPA was used. No additional lesions were detected when a triple dose of Gd-DTPA was used. These results 1) confirm that enhanced spinal cord imaging does not significantly increase the detection of active lesions in MS, 2) they do not support the general application of triple dose Gd-DTPA when examining the SC but 3) suggest that further studies taking into account SC symptoms are necessary.

Adult↗

PubMed2000

Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study.

OBJECTIVE: Magnetisation transfer imaging (MTI) provides information about brain damage with increased pathological specificity over conventional MRI and detects subtle abnormalities in the normal appearing brain tissue, which go undetected with conventional scanning. Brain MRI and MTI findings were compared in patients with multiple sclerosis (MS) and systemic immune mediated diseases (SIDs) affecting the CNS to investigate their roles in understanding the nature of brain damage in these diseases. METHODS: Brain dual echo, T1 weighted and MTI scans were obtained in patients affected by systemic lupus erithematosus (SLE) with (NSLE, n=9) and without clinical CNS involvement (n=15), Behçet's disease (BD) (n=5), Wegener's granulomatosis (WG) (n=9), and antiphospholipid antibody syndrome (APLAS) (n=6). Ten patients with clinically definite MS and 15 healthy controls also underwent the same scanning protocol. Brain MRI and MT ratio (MTR) images of the same subject were coregistered and postprocessed to obtain MTR histograms of the whole brain and of the NABT. RESULTS: Brain hyperintense lesions were found in all patients with MS and with NSLE and in 5/15 patients with SLE, 5/9 with WG, 1/5 with BD, and 3/6 with APLAS. The lesion burden in the brain was significantly higher in patients with MS compared with all the other disease groups. All MTR histogram parameters were significantly different among patient subgroups. Patients with MS had significantly lower average MTR than all except patients with NSLE and significantly lower peak height and location than patients with SLE. patients with NSLE had significantly lower average MTR than patients with SLE. CONCLUSIONS: Microscopic brain tissue damage is relevant in patients with MS, but, apart from patients with NSLE, it seems to be absent in systemic immune mediated diseases, even in the presence of macroscopic MRI lesions or clinical evidence of CNS involvement.

Adult↗

PubMed2000

Effects of subinhibitory concentrations of moxifloxacin in an in-vitro dynamic model.

The postantibiotic effect (PAE), sub-MIC effect (SME) and postantibiotic sub-MIC effect (PASME) of moxifloxacin were investigated in an in-vitro dynamic model reproducing in-vivo elimination kinetics of the antibiotic. The PAE was induced by exposing strains of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and Klebsiella pneumoniae to 5 x MIC of the antibiotic for 1.5 hours. After induction, cultures were washed to eliminate the antibiotic and resuspended into the dynamic model either in the presence or absence of a subinhibitory concentration of the antibacterial agent of 0.5 x MIC. Unexposed controls were treated similarly. PASMEs were constantly longer than corresponding SMEs, but differences between them were not statistically significant. Both PASMEs (mean 11:17 hours, range from 8:17 to 14:57) and SMEs (mean 9:23 hours, range from 6:03 to 12:34) had an initial bactericidal effect and were significantly longer than PAEs (mean 1:31 hours, range from 0:21 to 2:14). The primary effect of moxifloxacin sub-MICs appears to be prevalent in PAE. The possibility of once-daily dosing of the drug is strengthened.

Anti-Infective Agents↗

PubMed2000

In-vitro activity of moxifloxacin combined with other antibacterials against methicillin-resistant Staphylococcus aureus.

Killing kinetic experiments were performed with moxifloxacin, a novel fluoroquinolone, vancomycin, clarithromycin, cotrimoxazole, gentamicin, rifampicin and with moxifloxacin in combination with each of the above drugs against six methicillin-resistant Staphylococcus aureus clinical isolates. Half of the strains were ciprofloxacin-resistant. The early bactericidal effect of moxifloxacin alone was substantially greater than that of the other tested drugs. No antagonism was observed between moxifloxacin and each of the other drugs. For each combination the mean decrease in the number of organisms (after 6 hours) was comparable to that achieved with moxifloxacin alone, however, when moxifloxacin was tested with gentamicin, a slight increase in the bactericidal effect was observed.

Anti-Infective Agents↗

PubMed2000

A new type of very low-power modulated laser: soft-tissue changes induced in osteoarthritic patients revealed by sonography.

Patients with symptomatic osteoarthritis of the cervical spine were studied by ultrasound examination. The region of interest was the soft connective tissue layer above the right and the left superior trapezium that revealed a significant difference in thickness between the left and right side. The aching side was treated with a new type of very low-power, modulated laser for 3 min. Immediately after application, the sonographic examination revealed a significant symmetrization of the subcutaneous tissue.

Aged↗

PubMed1999

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↗

PubMed1999

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↗