Emanuele Cassetta

A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure.

BACKGROUND AND METHODS Lateral internal sphincterotomy, the most common treatment for chronic anal fissure, may cause permanent injury to the anal sphincter, which can lead to fecal incontinence. We compared two nonsurgical treatments that avert the risk of fecal incontinence. We randomly assigned 50 adults with symptomatic chronic posterior anal fissures to receive treatment with either a total of 20 U of botulinum toxin injected into the internal anal sphincter on each side of the anterior midline or 0.2 percent nitroglycerin ointment applied twice daily for six weeks. RESULTS After two months, the fissures were healed in 24 of the 25 patients (96 percent) in the botulinum-toxin group and in 15 of the 25 (60 percent) in the nitroglycerin group (P=0.005). No patient in either group had fecal incontinence. At some time during treatment, five patients in the nitroglycerin group had transient, moderate-to-severe headaches that were related to treatment. None of the patients in the botulinum-toxin group reported adverse effects. Ten patients who did not have a response to the assigned treatment - 1 in the botulinum-toxin group and 9 in the nitroglycerin group - crossed over to the other treatment; the fissures subsequently healed in all 10 patients. There were no relapses during an average of about 15 months of follow-up. CONCLUSIONS Although treatment with either topical nitroglycerin or botulinum toxin is effective as an alternative to surgery for patients with chronic anal fissure, botulinum toxin is the more effective nonsurgical treatment.

A Comparison of Botulinum Toxin and Saline for the Treatment of Chronic Anal Fissure

Background Chronic anal fissure is a tear in the lower half of the anal canal that is maintained by contraction of the internal anal sphincter. Sphincterotomy, the most widely used treatment, is a surgical procedure that permanently weakens the internal sphincter and may lead to anal deformity and incontinence. Methods We conducted a double-blind, placebo-controlled study of botulinum toxin for the treatment of chronic anal fissure in 30 consecutive symptomatic adults. All the patients received two injections (total volume, 0.4 ml) into the internal anal sphincter; the treated group (15 patients) received 20 U of botulinum toxin A, and the control group (15 patients) received saline. Success was defined as healing of the fissure (formation of a scar), and symptomatic improvement was defined as the presence of a persistent fissure without symptoms. Results After two months, 11 patients in the treated group and 2 in the control group had healed fissures (P = 0.003); 13 in the treated group and 4 in the cont...

Mapping distributed sources of cortical rhythms in mild Alzheimer's disease. A multicentric EEG study

The study aimed at mapping (i) the distributed electroencephalographic (EEG) sources specific for mild Alzheimers disease (AD) compared to vascular dementia (VaD) or normal elderly people (Nold) and (ii) the distributed EEG sources sensitive to the mild AD at different stages of severity. Resting EEG (10-20 electrode montage) was recorded from 48 mild AD, 20 VaD, and 38 Nold subjects. Both AD and VaD patients had 24-17 of mini mental state examination (MMSE). EEG rhythms were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical EEG sources were modeled by low resolution brain electromagnetic tomography (LORETA). Regarding issue i, there was a decline of central, parietal, temporal, and limbic alpha 1 (low alpha) sources specific for mild AD group with respect to Nold and VaD groups. Furthermore, occipital alpha 1 sources showed a strong decline in mild AD compared to VaD group. Finally, distributed theta sources were largely abnormal in VaD but not in mild AD group. Regarding issue ii, there was a lower power of occipital alpha 1 sources in mild AD subgroup having more severe disease. Compared to previous field studies, this was the first investigation that illustrated the power spectrum profiles at the level of cortical (macroregions) EEG sources in mild AD patients having different severity of the disease with respect to VaD and normal subjects. Future studies should evaluate the clinical usefulness of this approach in early differential diagnosis, disease staging, and therapy monitoring.

Elevation of serum copper levels in Alzheimer’s disease

Objective To determine whether serum trace metals and oxidative species are related to abnormal cognition in AD. Methods The authors studied serum peroxides, copper, iron, transferrin, and antioxidant capacity in 79 patients with AD (mean age 74.3 years; 25 men, 54 women) and in 76 cognitively normal individuals (mean age 70.1 years; 33 men, 43 women). The relation of these oxidative and trace metals to APOE &egr;4 allele frequency, neuropsychological performance, and cerebrovascular or atrophic burden, as estimated by brain MRI and ultrasonography of cerebral vessels, was evaluated. Results Copper level was higher (p < 0.001) in subjects with AD than control subjects (specificity = 95%, sensitivity = 60%) with a cutoff serum level of 16 &mgr;mol/L (1.02 mg/L). An increase of 1 &mgr;mol/L in serum copper accounted for 80% of the risk of having AD and correlated with poor neuropsychological performance and medial temporal lobe atrophy (p < 0.03). Antioxidant capacity decreased and correlated with medial temporal lobe atrophy (p < 0.009) and with APOE &egr;4 allele (p = 0.004). Conclusions Copper may play a role in neurodegenerative processes in AD, and serum copper measurement may prove to be a peripheral diagnostic marker for AD.

CONVERSION FROM MILD COGNITIVE IMPAIRMENT TO ALZHEIMER'S DISEASE IS PREDICTED BY SOURCES AND COHERENCE OF BRAIN ELECTROENCEPHALOGRAPHY RHYTHMS

Objective. Can quantitative electroencephalography (EEG) predict the conversion from mild cognitive impairment (MCI) to Alzheimers disease (AD)? Methods. Sixty-nine subjects fulfilling criteria for MCI were enrolled; cortical connectivity (spectral coherence) and (low resolution brain electromagnetic tomography) sources of EEG rhythms (delta=2-4 Hz; theta=4-8 Hz; alpha 1=8-10.5 Hz; alpha 2=10.5-13 Hz: beta 1=13-20 Hz; beta 2=20-30 Hz; and gamma=30-40) were evaluated at baseline (time of MCI diagnosis) and follow up (about 14 months later). At follow-up, 45 subjects were still MCI (MCI Stable) and 24 subjects were converted to AD (MCI Converted). Results. At baseline, fronto-parietal midline coherence as well as delta (temporal), theta (parietal, occipital and temporal), and alpha 1 (central, parietal, occipital, temporal, limbic) sources were stronger in MCI Converted than stable subjects (P<0.05). Cox regression modeling showed low midline coherence and weak temporal source associated with 10% annual rate AD conversion, while this rate increased up to 40% and 60% when strong temporal delta source and high midline gamma coherence were observed respectively. Interpretation. Low-cost and diffuse computerized EEG techniques are able to statistically predict MCI to AD conversion.

Botulinum toxin for chronic anal fissure

Botulinum toxin can chemically denervate striated muscle. Botulinum toxin A (15 U) was used to treat ten patients with chronic anal fissure by injection in the internal sphincter. In seven patients, the lesion healed at 2 months after treatment; one relapsed at 3 months. In one patient the lesion healed at 1 month, but partly relapsed a month later. Mild faecal incontinence lasting for 1 day was observed in one patient. We propose that botulinum toxin injections in the internal anal sphincter be considered an alternative approach to surgical therapy of anal fissure.

Excess of serum copper not related to ceruloplasmin in Alzheimer disease

Objective: To assess the role of serum copper in relation to ceruloplasmin and other peripheral markers of inflammation in Alzheimer disease (AD). Methods: The authors studied serum levels of copper, ceruloplasmin, and transferrin, as well as total peroxides, antioxidants, and other peripheral markers of inflammation in 47 patients with AD, 24 patients with vascular dementia (VaD), and 44 healthy controls. Biochemical variables were related to the patients’ and controls’ clinical status. Results: The authors found that copper (p < 0.001), peroxides (p = 0.026), and ceruloplasmin (p = 0.052) were increased and TRAP was decreased (p = 0.006) in patients with AD, while no other markers of inflammation were altered. The calculation of the ratio between copper and ceruloplasmin suggested the presence in the serum of AD patients, but not of VaD or normal controls, of a large pool of non-ceruloplasmin-bound copper. Conclusions: Changes in the distribution of the serum copper components, consisting of an increase of a copper fraction not explained by ceruloplasmin, seem to be characteristic of Alzheimer disease and may be implicated in the pathogenesis of the disease.

Botulinum toxin injections in the internal anal sphincter for the treatment of chronic anal fissure: long-term results after two different dosage regimens.

OBJECTIVE To investigate the effects of two different dosage regimens of botulinum toxin to induce healing in patients with idiopathic anal fissure. SUMMARY BACKGROUND DATA Chronic anal fissure is maintained by contraction of the internal anal sphincter. Sphincterotomy, which is successful in 85% to 95% of patients, permanently weakens the sphincter and therefore might be associated with anal deformity and incontinence. METHODS Fifty-seven consecutive outpatients were evaluated. Type A botulinum toxin was injected into the internal anal sphincter. RESULTS Patients were divided into two treatment groups based on the number of botulinum toxin units injected. Patients in the first group were treated with 15 units and retreated with 20 units. Patients in the second group were treated with 20 units and retreated with 25 units. Two months after treatment, 10 patients in the first group and 23 patients in the second group had a healing scar. Symptomatic improvement was observed in 13 patients in the first group and in 24 patients in the second group. Statistical analysis showed that resting anal pressure varied from baseline values as a function of treatment; in contrast, the treatment had no effect on maximum voluntary pressure. Long-term healing was achieved in 13 patients in the first group and in all patients in the second group who underwent a complete treatment. CONCLUSIONS Botulinum toxin is safe and effective in the treatment of anal fissure. It is less expensive and easier to perform than surgical treatment. No adverse effects resulted from injections of the toxin. The higher dosage is effective in producing long-term healing without complications.

Longitudinal prognostic value of serum “free” copper in patients with Alzheimer disease

Background: Serum copper not bound to ceruloplasmin (“free”) appears slightly elevated in patients with Alzheimer disease (AD). We explored whether a deregulation of the free copper pool can predict AD clinical worsening. Methods: We assessed levels of copper, iron, zinc, transferrin, ceruloplasmin, peroxides, total antioxidant capacity, free copper, and apolipoprotein E genotype in 81 patients with mild or moderate AD, mean age 74.4, SD = 7.4 years, clinically followed up after 1 year. The association among biologic variables under study and Mini-Mental State Examination (MMSE) (primary outcome), activities of daily living (ADL), and instrumental activities of daily living (IADL) (secondary outcomes) performed at study entry and after 1 year were analyzed by multiple regression. Results: Free copper predicted the annual change in MMSE, adjusted for the baseline MMSE by means of a linear regression model: it raised the explained variance from 2.4% (with only sex, age, and education) to 8.5% (p = 0.026). When the annual change in MMSE was divided into <3 or ≥3 points, free copper was the only predictor of a more severe decline (predicted probability of MMSE worsening 23%: odds ratio = 1.23; 95% confidence interval = 1.03–1.47; p = 0.022). Hyperlipidemic patients with higher levels of free copper seemed more prone to worse cognitive impairment. Free copper at baseline correlated with the ADL and IADL clinical scales scores at 1 year. Conclusions: These results show an association between copper deregulation and unfavorable evolution of cognitive function in Alzheimer disease. Further research is needed to establish whether copper is an independent risk factor for cognitive decline.

Influence of botulinum toxin site of injections on healing rate in patients with chronic anal fissure

BACKGROUND Botulinum toxin induces healing in patients with idiopathic anal fissure. METHODS Fifty patients affected by posterior anal fissure were treated with 20 units of botulinum toxin, injection in the internal anal sphincter on each side of the posterior midline (group I) or on each side of the anterior midline (group II). RESULTS At 2 months evaluation, a healing scar was observed in 15 patients of group I and in 22 patients of group II(P = 0.025). Resting anal pressure was significantly different from the baseline values at 1-month as well as at 2-month check-ups in both groups, but the values were significantly lower in patients of group II. CONCLUSIONS The intersite comparison revealed that anterior injection of the internal anal sphincter resulted in improved lowering of resting anal pressure and produced an earlier healing scar.