Safety and potential effectiveness of daunorubicin-containing liposomes in patients with advanced recurrent malignant CNS tumors.
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Antibiotics, Antineoplastic↗
Biomedical subjects
M Eoli
Publications and source records attributed to M Eoli.
Locally delivered chemotherapy and repeated surgery can improve survival in glioblastoma patients.
We treated 54 patients, newly diagnosed for glioblastoma, with systemic chemotherapy (carmustine (BCNU) 100 mg/m2 and cisplatin 90 mg/m2 every 6 weeks) and radiotherapy soon after surgery. In 10 cases the treatment was combined with locoregional chemotherapy (1 mg bleomycin on days 1-2, and 3 mg mitoxantrone on day 3, repeated every 20 days) administered from an Ommaya reservoir. At tumor recurrence, all patients were treated with procarbazine, lomustine and vincristine (PCV); 15 of 54 were reoperated and treated with locoregional chemotherapy. The median time to disease progression (TTP) and overall survival time (ST) for the whole group were 10.8 and 23.1 months, respectively. The ST of the 15 reoperated patients who also received locoregional treatment at disease recurrence was 27.6 months; this was significantly longer than that of patients not reoperated and not treated locally (log-rank p=0.04). The results in our reoperated subgroup support the opinion that a second operation could be suitable if it is part of the whole program of treatment.
Antineoplastic Combined Chemotherapy Protocols↗
Affective disorders and multiple sclerosis: a controlled study on 65 Italian patients.
A high prevalence of major mood disorders in multiple sclerosis (MS) patients has been reported. In this study, we investigated the frequency of previous or present major mood disorders in 65 patients with clinically definite multiple sclerosis (Poser criteria) and in 31 polyneuropathy (PNP) patients. All patients underwent a questionnaire designed after DSM-IV definitions for major mood disorders. A higher lifetime risk for development of a major mood disorder was evident in MS patients (log rank test, p<0.001). Of all MS patients with a major mood disorder, at least 34% had one first-degree relative affected by a mood disorder, while the corresponding figure was 14% among PNP cases. Our data confirm the high lifetime risk for depression in MS patients and suggest that, at least in a subset of MS patients with depression, the genetic basis for depression operates with similar mechanisms as those at work in families with primary depression. However, this is not necessarily true for other subsets of depressed MS patients' families.
Adolescent↗
Cyclophosphamide in chronic progressive multiple sclerosis: a comparative study.
No effective treatment is presently available for progressive multiple sclerosis (MS). Cyclophosphamide (CFX), a cytotoxic immunosuppressive drug widely used in systemic dysimmune diseases, has been proposed for the treatment of multiple sclerosis with different schedules and controversial results. To evaluate the safety and clinical efficacy of CFX, we compared three different treatment schedules in patients with progressive MS: induction followed by bimonthly boosters for one year (17 patients); bimonthly boosters for one year without previous induction (15 patients); and monthly boosters for one year (21 patients). Survival analysis showed that the percentage of stable patients was significantly higher in the first and third treatment schedule groups. Myelotoxicity occurred in patients treated with induction and boosters (Group A). A high incidence of broncopneumonia was observed in patients undergoing the second treatment schedule (Group B). No major effects were observed in patients treated with monthly boosters (Group C). Response to treatment was limited to secondary progressive form. This study suggests that monthly treatment with CFX might be safely administered in progressive MS patients; its clinical efficacy must be confirmed by an appropriately designed clinical trial.
Adult↗
Meningo-cortical calcifying angiomatosis and celiac disease.
A woman with ophthalmic migraine was found to have bilateral cerebellar and cerebral calcifications. She progressively developed severe intracranial hypertension, with swelling of the brain and downward transtentorial and tonsillar herniation. Because steroid treatment was ineffective, the right occipital pole was resected. Histological study demonstrated meningo-cortical calcifying angiomatosis. Within 2 months, brain swelling and papilledema disappeared. Subtle signs of malabsorption led to the hypothesis of celiac disease, confirmed by jejunal biopsy. Similar cerebral histological findings have been reported in the brain of two young patients affected by epilepsy and celiac disease. The association between cerebral calcifications and celiac disease is peculiar; the pathogenetic relationship is unknown.
Adult↗
Immunological monitoring of azathioprine treatment in multiple sclerosis patients.
Despite the longstanding clinical use of azathioprine as an immunosuppressive agent in multiple sclerosis, little is known about the action of this drug on a number of parameters of putative pathogenic relevance in the disease. Eleven patients with multiple sclerosis, treated with azathioprine 2.5-3 mg/kg per day, and six untreated patients were studied with serial blood sampling for 1 year. The following immunological parameters were investigated: peripheral blood lymphocyte subsets, natural killer activity, serum IgG, IgM, ICAM-1 and tumour necrosis factor alpha (TNF-alpha). The most relevant changes included a decrease in CD3- CD56+ cells, an increase in CD4+ CD45RA+ cells and a decrease in TNF-alpha levels only in treated patients, while no changes occurred in untreated patients over a 1-year period. The decrease in TNF-alpha levels and the increase in "suppressor-inducer" lymphocytes could reduce chronic inflammation in multiple sclerosis, and paralleled an overall favourable clinical response to azathioprine treatment in our patients.
Azathioprine↗
Low serum interleukin-10 levels in multiple sclerosis: further evidence for decreased systemic immunosuppression?
Serum interleukin 10 (IL10) levels were assessed in patients with multiple sclerosis who were either in a stable or active clinical condition. The levels were compared with values in healthy controls. Lower IL10 levels than in controls were seen in multiple sclerosis patients, regardless of clinical disease activity. Low IL10 levels were also seen in patients with systemic lupus erythematosus. No clear-cut relationships emerged between IL10 levels and those of tumour necrosis factor alpha and transforming growth factor beta, or between IL10 and lymphocyte subsets in peripheral blood.
Adult↗
Does a placebo-effect exist in clinical trials on multiple sclerosis? Review of the literature.
To verify whether the outcome in placebo-treated MS patients actually corresponds to that expected on the basis of the natural history and pretrial evolution of the disease, we here review the results of clinical trials conducted according to a placebo-controlled, randomized design, regardless of the experimental therapy used. The frequency of relapse in remitting-relapsing patients decreases during follow-up, and disability in progressive cases increases more slowly than before enrollment. These data should be borne in mind when evaluating the impact of experimental drugs on the natural course of the disease.
Clinical Trials as Topic↗
Parallel fluctuations of psychiatric and neurological symptoms in a patient with multiple sclerosis and bipolar affective disorder.
The case of a female patient affected by simultaneously onsetting multiple sclerosis and bipolar affective disorder at age 33 is reported. Over the following years, the patient displayed minor mood fluctuations but, at the ages of 41 and 42 years, respectively, she suffered from a major depressive and a manic episode, both of which were concomitant with a marked worsening in her neurological condition.
Adult↗
Racemose neurocysticercosis after chronic meningitis: effect of medical treatment.
A patient affected by racemous neurocysticercosis, occurring 5 years after the onset of chronic meningitis and followed by sequential MRI studies, is described. After ventriculo-peritoneal shunt, he was successfully treated with Praziquantel and Albendazole. This case may contribute to understand the natural history of the disease and stress the efficacy of medical versus surgical treatment of this lifethreatening disease.
Adult↗
Analysis of HLA-class II DQA1, DQB1, DRB1 and DPB1 in Italian multiple sclerosis patients.
We studied the allelic constitution at the HLA class II DQA1, DQB1, DRB1 and DPB1 in 94 Italian multiple sclerosis (MS) patients and 98 controls. No significant increase in the frequency of DR2 alleles was detected among MS patients, as previously observed both in European and some Italian studies. A slight increase was found for the DQA1*0301 and DQB1*0602 alleles in the MS patients. No significant association was found with the glutamine residue at position 34 of the DQ alpha chain, which was noted previously in MS patients from northern Europe.
Alleles↗
Evidence of linkage between susceptibility to multiple sclerosis and HLA-class II loci in Italian multiplex families.
To verify whether multiallelic polymorphisms belonging to HLA class II genes are linked to multiple sclerosis (MS) in the Italian population, we studied 28 multiplex MS families originating from different areas of Italy. Allelic characterization was carried out by analysis of RFLPs and oligonucleotide typing. Evidence supporting the existence of linkage between MS susceptibility and the HLA class II loci DRB1, DQA1 and DQB1 was provided using two non-parametric tests, affected sib-pair analysis, and affected-pedigree-member (APM) analysis. The APM analysis also suggested the existence of genetic heterogeneity for the HLA class II loci and MS susceptibility in our series. Linkage disequilibrium between MS susceptibility and the haplotype DRB1*1501,DQA1*0102,DQB1*0602 was demonstrated by applying the transmission linkage disequilibrium test to our families. Finally, lod score analysis suggests that in our Italian families, MS susceptibility is conferred by HLA class II alleles according to a low-penetrance autosomal recessive mode of inheritance.
Alleles↗
The myelin basic protein gene is not a major susceptibility locus for multiple sclerosis in Italian patients.
To verify whether multiallelic polymorphism adjacent to the gene encoding for myelin basic protein is associated with or linked to multiple sclerosis in Italians, we studied 54 sporadic patients, 55 control subjects and 18 families with two or more affected individuals. Allelic typing was carried out by analysis of fragment length polymorphisms after DNA amplification by the polymerase chain reaction. The presence of linkage with the disease was tested according to either autosomal dominant or autosomal recessive modes of inheritance, and with or without the introduction of liability classes accounting for the age of the individuals. Furthermore sib-pair analysis was performed in 11 siblings. No evidence for association or linkage between the myelin basic protein gene polymorphism and multiple sclerosis was found. Our data indicate that in the Italian population the myelin basic protein gene does not play a major role in conferring genetic susceptibility to multiple sclerosis, and suggest that the latter is a heterogeneous phenomenon, possibly influenced by the different ethnic origin of the populations which have been investigated.
Adult↗
Serial evoked potentials in multiple sclerosis bouts. Relation to steroid treatment.
Serial recordings of multimodal sensory (visual, acoustic and somatosensory) evoked potentials were made in 19 relapsing-remitting Multiple Sclerosis patients enrolled in a clinical trial designed to evaluate the efficacy of dexamethasone versus high- and low-dose methylprednisolone in acute multiple sclerosis bouts. Electrophysiological and clinical evaluations were performed at the onset of therapy and until 6 months after the end of treatment. Using an arbitrary Evoked Potentials score that takes into account both latency and waveform alterations, we found a positive correlation between evoked potentials and clinical disability scores. Furthermore, different electrophysiological profiles were detected in the three therapeutic subgroups. Evoked potentials may be useful for monitoring acute Multiple Sclerosis bouts and evaluating the effect of therapy.
Adult↗
No linkage between multiple sclerosis and the T cell receptor alpha chain locus.
Susceptibility to multiple sclerosis (MS) is genetically determined but it is thought that more than one gene contributes to development of the disease. We report a study of linkage to one candidate, the T cell receptor alpha chain locus, on chromosome 14, in affected sibling pairs. Markers with high polymorphism information contents were used to assign haplotypes identical by descent and state. Forty nine pairs were studied using restriction fragment length polymorphisms (RFLP) and 82 pairs were investigated using a microsatellite repeat polymorphism. In neither case did genotype or haplotype sharing differ significantly from expected rates. Stratification of patients according to DR15 status did not alter the distribution of haplotypes in affected siblings. We conclude that the T cell receptor alpha locus is not linked to susceptibility in patients with MS from the United Kingdom.
Base Sequence↗
Double-blind trial of dexamethasone versus methylprednisolone in multiple sclerosis acute relapses.
The efficacy of dexamethasone (DX) and methylprednisolone (MP) at high (HD) and low (LD) dose in acute multiple sclerosis (MS) relapses was evaluated by a double-blind trial in 31 patients followed for 1 year. DX and HDMP were similarly efficacious in promoting recovery, while LDMP was ineffective in the short-term outcome and was followed by an early clinical reactivation. The different outcomes seem to be related to different immunomodulating effects, mainly on cerebrospinal fluid (CSF) IgG synthesis and on peripheral blood and CSF CD4+ lymphocyte subsets.
Adult↗
Immunological monitoring and clinical evaluation in cyclophosphamide-treated progressive multiple sclerosis patients.
15 patients with progressive Multiple Sclerosis (MS) were treated by an induction Cyclophosphamide (CFX) schedule followed by bimonthly boosters over one year. Of the 14 patients who completed the trial, only two displayed worsening of neurological status. Cerebrospinal fluid (CSF) total protein, IgG/Alb ratio and IgG index decreased at 6 months and were still low at the end of the treatment. Pretreatment percentages of PB CD8+ and CD4+CD45RA+ lymphocytes were lower in MS patients in comparison with healthy controls. However, no significant shifts occurred in percentage of PB CD4+, CD4+CD45RA+, CD4+CD45RA-, CD8+ lymphocytes of MS patients during immunosuppressive treatment. The lack of changes in the investigated immunological parameters contrasts with the good clinical response and the low rate of serious side effects during this treatment schedule.
Antigens, CD↗
High-dose methylprednisolone treatment-induced changes in immunological parameters in progressive MS patients.
The effect of High-Dose Methylprednisolone (HD-MP) treatment on Peripheral Blood (PB) and Cerebrospinal Fluid (CSF) immune parameters was investigated in 9 patients with relapsing-progressive Multiple Sclerosis (MS). Short-time effects included reduction of the percentage of CD3+, CD4+ and CD4+CD45RA+ PB lymphocytes and increase in CD3-CD56+ cells. At the end of the treatment, only increase in PB CD19+ and in CSF CD8+, CD8+CD28+ and decrease of CSF CD4+CD45RA- and serum IL2R levels were observed. No changes in CD11a+CD4+, CD18+CD14+ PB cells were observed after treatment. The results further stress the complex and multifaceted action of HD-MP on immune parameters.
Adult↗