Safety and tolerability of cyclophosphamide 'pulses' in multiple sclerosis: a prospective study in a clinical cohort

To assess the safety and tolerability of cyclophosphamide (CTX) 'pulse' therapy in progressive or very active multiple sclerosis (MS), we reviewed our experience in a cohort of MS patients who have been treated and prospectively followed-up in our Department since 1997. One hundred and twelve patients received intravenous CTX in monthly 'pulses' for 12 months at the dosage of 700 mg/m2 of body surface, then bimonthly for another 12 months. We evaluated the frequency and the severity of side-effects, as well as overall tolerability by the patient perspective using a visual analogue scale (VAS). Side-effects resulted in the discontinuation of therapy in 20 (18%) cases. Serious side-effects were observed in 24 patients (21.4%), most commonly definitive amenorrhea (33.3% of fertile women), hypogammaglobulinemia (5.4%), and hemorrhagic cystitis (4.5%). Malignancies were diagnosed in four (3.6%) subjects, three of whom were previously treated with azathioprine (AZA). Finally, 81.8% of the patients judged the treatment regimen as very or relatively acceptable and tolerable. Our data point to a reasonable safety and tolerability of CTX 'pulse' therapy. Further trials are needed to definitively assess the efficacy of CTX as an alternative therapeutic option for progressive or very active MS.     

Multimodal Migraine Treatment: Does Thermal Feedback Add to the Outcome?

SYNOPSIS
This study was carried out to examine the therapeutic necessity of thermal feedback training in a multimodal treatment program for migraine headache. Twenty-one patients with frequent (at least two per month) migraine headaches or combined migraine-tension headaches were randomly assigned to one of two conditions: (1) autogenic relaxation training followed by stress-coping training; (2) the same treatment package supplemented with thermal feedback.
Results indicated the equivalent effectiveness of both treatments in ameliorating headache activity and reducing medication use. These outcomes were stable 7 months after treatment. Between-group comparisons on clinical improvement and on temperature performance with autogenic relaxation, as well as findings from post-treatment interviews, led to the conclusion that thermal feedback training can be excluded without weakening the program's therapeutic efficacy.
In general the results suggest that thermal feedback per sé does not add to the treatment outcomes obtainable with general relaxation training, and that for patients characterized by high achievement-motivation and sensitivity to initial failure a feedback regimen might even be counterproductive. Both findings need further experimental clarification.     

Choline acetyltransferase and acetylcholinesterase abnormalities in senile dementia: Importance of biochemical measurements in human post-mortem brain specimens

Choline acetyltransferase and acetylcholinesterase have been assessed in human aging brains, in demented and agonal states. Choline acetyl transferase decreased during aging in normal brain when measured in the cerebral cortex. Choline acetyltransferase was also reduced in several other brain areas in patients with Alzheimer's disease and in one patient with Creutzfeldt-Jakob disease. Choline acetyltransferase was also reduced in bronchopneumonia and in some terminal conditions. On the contrary, the activity was not reduced in patients who died after cerebrovascular accidents. Acetylcholine esterase, although it followed the general trend of choline acetyltransferase, did not yield significant results.     

Double-blind, crossover, placebo-controlled clinical trial with L-acetylcarnitine in patients with degenerative cerebellar ataxia

Despite the different genetic defects underlying degenerative ataxias, it has been suggested that mitochondrial energy production and antioxidative metabolism dysfunction may be common biochemical alterations related to these diseases. Acetylcarnitine, a cholinomimetic substance, is involved in oxidative metabolism and is a potential source of acetyl groups for the synthesis of acetylcholine in the mammalian brain. To determine whether treatment with L-acetylcarnitine may improve some clinical conditions of patients with ataxia, a double-blind crossover study with L-acetylcarnitine was performed in 24 patients with degenerative cerebellar diseases. Patients were selected from an ongoing prospective follow-up study at the Department of Neurology at the University of Florence, Italy. Each treatment phase with L-acetylcarnitine or placebo lasted 6 months, after which patients were crossed over to the other treatment phase. Ataxia was documented and quantified with use of a clinical score. After the trial, we observed a statistically significant improvement of some symptoms and a slow progression of the disease in both groups of patients.     

Management and long-term prognosis of Dieulafoy lesion

BACKGROUND: The Dieulafoy lesion is an important cause of gastrointestinal (GI) hemorrhage. Optimal treatment and long-term outcome are unknown. This study aimed to characterize the presentation of the Dieulafoy lesion and to summarize the results and report the long-term outcome of endoscopic therapy. METHODS: Data regarding diagnosis, treatment and outcomes were derived from our GI Bleed Team database, patient records and follow-up correspondence. RESULTS: Ninety Dieulafoy lesions were identified in 89 patients after a mean of 1.9 endoscopies. Their mean age was 72 years. Thirty-four percent of lesions were extragastric. Median transfusion requirement was 5 units. Two patients exsanguinated and 3 required surgery; all others were initially successfully treated endoscopically (with or without epinephrine injection): heat probe (71 patients), band ligation (3), hemoclip (1), laser (2), bipolar probe (4), sclerotherapy (2) and epinephrine alone (2). Gastric perforation occurred in 1 patient following sclerotherapy. Thirty-day mortality was 13%, 4 related to hemorrhage and 5 related to comorbidity. During median follow-up of 17 months, 34 patients (42%) died. One patient had recurrent bleeding 6 years after operation. CONCLUSIONS: Dieulafoy lesion is relatively common and often extragastric. Endoscopic therapy is safe and effective. Long-term recurrence was not evident following endoscopic ablation. Follow-up after ablative therapy appears unnecessary.     

Ataxia-telangiectasia mutated (ATM) genetic variant in Italian centenarians

Lifespan is attributable to genetic factors and some studies have attempted to identify putative genes implicated in human longevity. Several genetic loci have been associated with longevity, but some of these are not replicable, probably due to the vast differences among ethnicities. We analyzed in 128 Italian long-lived individuals and 150 unrelated healthy subjects, the recently reported association between rs189037 in the ataxia-telangiectasia mutated gene promoter and longevity in Chinese nonagenarians/centenarians. Our study confirms the association between the rs189037 C/T genotype and longevity in Italian centenarians, with an odds ratio of 1.85 (95 % CI 0.99–3.45). To understand the genetic basis for longevity is an extraordinarily difficult task, and therefore it is important to replicate any positive findings, especially if detected in other ethnic groups, in order to reach reliable conclusions on the real effect that candidate genes have on longevity.     

Apolipoprotein E and α1-antichymotrypsin polymorphism in Alzheimer's disease

A recent observation has shown that a common polymorphism in the α₁-antichymotrypsin (ACT) gene modifies the apolipoprotein E (ApoE) ε4-associated Alzheimer's disease (AD) risk identifing the combination of the ACT/AA and ApoE ε4/ε4 genotypes as a potential susceptibility marker for AD. We analyzed the segregation of the ApoE and ACT polymorphism in sporadic and familial AD patients. In none of the sporadic AD patients did we find the combination of the ACT/AA and ApoE ε4/ε4 genotypes. The frequency of ApoE ε4/ε4 homozygosity in the AD sample resulted highest for the ACT/TT genotype (17.6%). Our data fail to confirm any additional association with AD beyond the ApoE ε4 allele with any ACT genotype, suggesting that ACT does not represent an additional risk factor for AD.