Evaluation of lithium response in episodic cluster headache: a retrospective case series

Objective.— In this study, we attempted to evaluate the response to lithium treatment and its tolerability in the prevention of episodic cluster headache (CH) and to identify clinical predictors of response. Background.— Verapamil and lithium are the most widely used drugs in the prevention of CH attacks. Lithium is considered a second‐line treatment in part because of its potentially severe adverse drug reactions (ADRs). Evidence for the efficacy of lithium in CH prevention is greater in chronic than in episodic patients. In addition, because of its narrow therapeutic window and ADRs (which can be significantly reduced with proper periodical monitoring of blood levels), lithium is recommended only in chronic CH, when other drugs are ineffective or potentially harmful. Methods.— Our primary aim was to determine whether lithium reduced the number of attacks per day (attack frequency). We compared attack frequency in 3 periods: run‐in, the first, and the second week of lithium treatment. Responders were defined as patients showing at least a 50% reduction in attack frequency. Results.— Lithium response was evaluated in 26 patients. Treatment led to a significant reduction in attack frequency within 2 weeks in a percentage of 77% of responders and 23% of nonresponders. Responders and nonresponders did not differ in terms of demographic and clinical characteristics. Only 15% of patients experienced mild ADRs. Conclusion.— Our study provides additional evidence on the effectiveness of lithium in the prevention of episodic CH. It also shows the tolerability of lithium, given the short duration of treatment and low dosage.     

High-dose idarubicin, busulphan and melphalan for autologous stem cell transplantation in multiple myeloma responsive to DAV chemotherapy: comparison with a historical control

Since 1997, 32 newly diagnosed multiple myeloma patients responsive to DAV chemotherapy were autografted with idarubicin-intensified busulphan-melphalan (ida-bu-mel). Main endpoints of the study were transplant-related toxicity, overall survival (OS) and progression-free survival (PFS). The results were compared with a historical control group of 38 patients treated with the 'standard' bu-mel regimen. Concerning time to engraftment, no significant difference was observed between the two groups, while toxicity was significantly higher in the intensive conditioning group, regarding grade IV mucositis, duration of profound neutropenia, incidence of infections and platelet requirement. Five-year OS and PFS are 73 versus 78% and 37 versus 48% for the intensive and standard regimen, respectively (p value not significant). The ida-bu-mel schedule appears to be a feasible and effective regimen for newly diagnosed multiple myeloma patients; nevertheless, no apparent benefit in OS and PFS arises from the comparison with a historical control treated with standard bu-mel, which is better tolerated and at least equally effective.     

Polymorphisms in MT1a gene coding region are associated with longevity in Italian Central female population

Metallothioneins (MTs) play a pivotal role in zinc-related cell homeostasis because of their high affinity for zinc, which is in turn fundamental for immune response and antioxidant activity. MTs regulate zinc homeostasis by binding zinc and releasing zinc at the occurrence for immune response. The zinc release by MT is very limited in chronic inflammation and ageing. Some polymorphisms of MTs gene, in particular MT1a sub-isoform, may affect this release that is a problem still unresolved in ageing. The screening in the present paper of two polymorphisms in MT1a gene has revealed for the first time that the polymorphism corresponding to a A/C (Asp/Thr) transition at 647 nt position in the Mt1a coding region is the more involved in the longevity, at least in old women, rather than the other corresponding to A/G (Lys/Arg) transition at 1,245 nt position. Concomitantly, for the +647 MT1a polymorphism, old and very old female with Asp/Asp genotype (called C-carriers) display higher zinc release by MT (detected by Zinpyr-1 fluorescent probe in presence of NO donor), low MT levels and reduced IL-6 plasma concentrations, suggesting its involvement in longevity and in lower inflammatory status. This fact is confirmed by the analysis of haplotypes in which the allele Asp is more involved in longevity. Therefore the +647 MT1a polymorphism more affects MTs induction and zinc release, which are indispensable to undertake the inflammatory status under control and subsequently to reach healthy longevity.Presented at the ZincAge Conference, Madrid, February 10–13, 2006.     

Benign breast lesions at risk of developing cancer—A challenging problem in breast cancer screening programs

BACKGROUND:

Cytology and core‐needle biopsies are not always sufficient to exclude malignancy in benign breast lesions (BBL) that are at risk of developing cancer, and open biopsy often is mandatory. In screening programs, open biopsies performed for lesions that are at risk of developing malignancy are considered benign. The authors of this report evaluated the impact of the screen‐detected BBL at risk of developing cancer that were counted in the quota of benign breast open biopsies in the Breast Cancer Screening Program of Verona.

METHODS:

Benign open biopsies were subdivided into 4 groups according to their risk of developing cancer: Histo1, normal histology; Histo2, ‘pure’ BBL (fibroadenoma, fibrocystic disease, mastitis, adenosis); Histo3, BBL with a low risk of developing cancer (radial scar, papilloma, papillomatosis, phyllodes tumor, mucocele‐like lesion); and Histo4, BBL with a high risk of developing cancer (atypical columnar cell hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia).

RESULTS:

Of 510 open biopsies, 83 biopsies were benign, and the ratio of benign to malignant biopsies was 1:5. Histo1 was observed in 4.8% of all benign open biopsies, Histo2 was observed in 37.4%, Histo3 was observed in 31.3%, and Histo4 was observed 26.5%.

CONCLUSIONS:

BBL at risk of developing cancer may be numerous in screening programs. It is inappropriate to include BBL at risk of developing cancer in the overall benign open biopsy rate. The authors propose separating pure BBL from lesions at higher risk of developing cancer. To date, there is no evidence to support the premise that detecting high‐risk proliferative lesions leads to benefits in terms of reduced mortality; however, these lesions need to be counted separately for future evaluations. Cancer 2009. © 2008 American Cancer Society.     

Macromolecular permeability of chick wing microvessels: an intravital confocal study

The development of the vertebrate limb requires the formation of a normal vasculature to nurture the soft and hard tissue phenotypes. The pattern of embryonic limb bud vessels has been extensively studied, but little is known about the permeability characteristics of the developing circulation. In the present study, the microvascular endothelial cell phenotype was examined by in vivo confocal microscopy following the systemic injection of a graded series of fluorescent dextrans (40,000, 70,000, 150,000 molecular weight) into chick embryos at stages 21–23 in order to determine how selective is the endothelial lining of microvessels as a partition between the blood vessels and the interstitium. Videodensitometry, over a gray scale range of 0–255, was used to quantitate the amount of tracer found within the interstitial compartment of the limb. The tracers of larger molecular weight (70,000, 150,000) were confined exclusively to the vascular lumina, whereas that of smaller molecular weight (40,000) was found to cause perivascular brightening due to extravasation into the surrounding interstitium. The reported differences in permeability were not dependent upon the stage of the embryo used in this study, but were due to the size of the tracer. These data indicate that embryonic wing microvessels demonstrate permselectivity to macromolecular efflux across the endothelium. The present results provide a basis for additional studies concerned with the dynamic characteristics of the limb microvasculature and challenge our concepts about the role of diffusible morphogens in vertebrate limb development.     

Adherence to Sublingual Immunotherapy

Adherence is a major issue in any medical treatment. Allergen immunotherapy (AIT) is particularly affected by a poor adherence because a flawed application prevents the immunological effects that underlie the clinical outcome of the treatment. Sublingual immunotherapy (SLIT) was introduced in the 1990s, and the early studies suggested that adherence and compliance to such a route of administration was better than the traditional subcutaneous route. However, the recent data from manufacturers revealed that only 13 % of patients treated with SLIT reach the recommended 3-year duration. Therefore, improved adherence to SLIT is an unmet need that may be achieved by various approaches. The utility of patient education and accurate monitoring during the treatment was demonstrated by specific studies, while the success of technology-based tools, including online platforms, social media, e-mail, and a short message service by phone, is currently considered to improve the adherence. This goal is of pivotal importance to fulfill the object of SLIT that is to modify the natural history of allergy, ensuring a long-lasting clinical benefit, and a consequent pharmaco-economic advantage, when patients complete at least a 3-year course of treatment.     

Benign childhood epilepsy with occipital paroxysms: neuropsychological findings

Benign childhood epilepsy with occipital paroxysms is classified among childhood benign partial epilepsies. The absence of neurological and neuropsychological deficits has long been considered as a prerequisite for a diagnosis of benign childhood partial epilepsy. Much evidence has been reported in literature in the latest years suggesting a neuropsychological impairment in this type of epilepsy, particularly in the type with Rolandic paroxysms. The present work examines the neuropsychological profiles of a sample of subjects affected by the early-onset benign childhood occipital seizures (EBOS) described by Panayotopulos. The patient group included 22 children (14 males and 8 females; mean age 10.1+/-3.3 years) diagnosed as having EBOS. The patients were examined with a set of tests investigating neuropsychological functions: memory, attention, perceptive, motor, linguistic and academic (reading, writing, arithmetic) abilities. The same instruments have been given to a homogeneous control group as regards sex, age, level of education and socio-economic background. None of the subjects affected by EBOS showed intellectual deficit (mean IQ in Wechsler Full Scale 91.7; S.D. 8.9). Results show a widespread cognitive dysfunction in the context of a focal epileptogenic process in EBOS. In particular, children with EBOS show a significant occurrence of specific learning disabilities (SLD) and other subtle neuropsychological deficits. We found selective dysfunctions relating to perceptive-visual attentional ability (p<0.05), verbal and visual-spatial memory abilities (p<0.01), visual perception and visual-motor integration global abilities (p<0.01), manual dexterity tasks (p<0.05), some language tasks (p<0.05), reading and writing abilities (p<0.01) and arithmetic ability (p<0.01). The presence of cognitive dysfunctions in subjects with EBOS supports the hypothesis that epilepsy itself plays a role in the development of neuropsychological impairment. Supported by other studies that have documented subtle neuropsychological deficits in benign partial epilepsy, we stress the importance of reconsidering its supposed "cognitive benignity", particularly in occipital types.