Genetic susceptibility to cutaneous melanoma in southern Switzerland: role of CDKN2A, MC1R and MITF.

BACKGROUND: Nearly 10% of all cases of cutaneous melanoma (CM) occur in patients with a personal or family history of the disease. OBJECTIVES: To obtain information about genetic predisposition to CM in Ticino, the southern region of Switzerland, a zone with moderate-to-high CM incidence. METHODS: We identified germline mutations in highly CM-associated genes (CDKN2A and CDK4) and low/medium-penetrance variants (MC1R and MITF) in patients with multiple primary CMs or individuals with one or more CM and a positive family history for CM or pancreatic cancer among first- or second-degree relatives. Healthy blood donors (n = 146) were included as a control group. RESULTS: From July 2010 to July 2012, 57 patients (41 pedigrees) were included. Twenty-six were melanoma-prone families (with at least two cases) and 15 had multiple CMs. Pancreatic cancer was found in six families. The CDKN2A mutation p.V126D was identified in seven patients (four families) with a founder effect, whereas CDKN2A A148T was detected in seven cases (five families) and seven healthy donors (odds ratio 2·76, 95% confidence interval 0·83-9·20). At least one MC1R melanoma-associated polymorphism was detected in 32 patients (78%) and 97 healthy donors (66%), with more than one polymorphism in 12 patients (29%) and 25 healthy donors (17%). The MITF variant p.E318K was identified in four patients from three additional pedigrees (7%) and one healthy control (0·7%). CONCLUSIONS: Inclusion criteria for the Ticino population for genetic assessment should follow the rule of two (two affected individuals in a family or a patient with multiple CMs), as we detected a CDKN2A mutation in almost 10% of our pedigrees (four of 41), MITF p.E318K in 7% (three of 41) and a higher number of MC1R variants than in the control population.

[Presence and influence of attention deficit hyperactivity disorder symptoms in adults with an eating disorder].

BACKGROUND: The coexistence of eating disorders (ED) and attention deficit hyperactivity disorder (ADHD) is common. The aim of the study was to quantify the presence of ADHD symptoms in adult patients with ED and evaluate any possible correlation between both symptomatologies. METHODS: Cross-sectional study of patients with ED. The following questionnaires were completed: the Eating Attitudes Test - 40 items (EAT-40), the Eating Disorder Inventory 3rd edition (EDI-3) and the abbreviated version of the Adult ADHD Self-Report Scale (ASRS v1.1). The patients who scored =12 points in ASRS v1.1 completed the Attention Deficit Hyperac-tivity Disorder Rating Scale (4th edition, ADHD-RS IV). RESULTS: 42.6% of the 108 patients scored =12 in the ASRS v1.1. These subjects scored higher in bulimia and in some scales of psychological maladjustment of the EDI-3, and those with binging and/or purging behaviours scored higher in Psychobi-ological disorders of the EAT-40 and in Body dissatisfaction and Eating disorder risk composite scales of the EDI-3. There were no differences in ADHD-RS IV between pure restrictive syndromes (n=13) and those with binging and/or purging behaviours (n=33). We found that, in cases with binge/purge symptoms, ADHD symptoms correlated higher with ED symptoms and with general psychological maladjustment. CONCLUSION: ADHD symptoms are common in the clinical population with ED, and more in groups with binge/purge symptoms, although they are not necessarily more intense. The correlation between ADHD symptoms and ED is higher in cases with binging and/or purging behaviours. ADHD symptoms involve more psychological maladjustment and more serious ED symptomatology in cases with binge/purge symptoms.

[Initial evaluation, diagnosis, staging, treatment, and follow-up of patients with primary cutaneous malignant melanoma. Consensus statement of the Network of Catalan and Balearic Melanoma Centers]. / Valoración inicial, diagnóstico, estadificación, tratamiento y seguimiento de los pacientes con melanoma maligno primario de la piel. Documento de consenso de la "Xarxa de Centres de Melanoma de Catalunya i Balears"

The consensus statement on the management of primary cutaneous melanoma that we present here was based on selection, discussion, review, and comparison of recent literature (including national and international guidelines). The protocols for the diagnosis, treatment, and follow-up used in the hospital centers throughout Catalonia and the Balearic Isles belonging to the Network of Catalan and Balearic Melanoma Centers were also considered. The main objective of this statement was to present the overall management of melanoma patients typically used in our region at the present time. As such, the statement was not designed to be an obligatory protocol for health professionals caring for this group of patients, and neither can it nor should it be used for this purpose. Professionals reading the statement should not therefore consider it binding on their practice, and in no case can this text be used to guarantee or seek responsibility for a given medical opinion. The group of dermatologists who have signed this statement was created 3 years ago with the aim of making our authorities aware of the importance of this complex tumor, which, in comparison with other types of cancer, we believe does not receive sufficient attention in Spain. In addition, the regular meetings of the group have produced interesting proposals for collaboration in various epidemiological, clinical, and basic applied research projects on the subject of malignant melanoma in our society.

Determination and in-process control of zolpidem synthesis by high-performance liquid chromatography.

A high-performance liquid chromatographic assay with diode-array detection has been developed for the in-process control of zolpidem synthesis and for the analysis of the drug and its synthetic intermediates. The separation uses a 4.6mm i.d. reversed-phase Kromasil C(18) (150 mm) column, 5 microm particle size with a gradient elution mode of acetonitrile and 0.02 M NH(4)OAc (adjusted to pH 8.0) as the mobile phase (flow rate 1.0 mlmin(-1)). The analysis is performed in 12 min. The method is simple, rapid and highly specific.

[Pharyngeal chordoma]. / Cordoma faríngeo.

Chordoma is a neoplasm arising from embryonal notochord remnants. It is infrequent and rarely located at the cervical level. The diagnosis is histological and immunohistochemical tests are required to differentiate it from other neoplasms. We report a case of pharyngeal chordoma treated with a transmandibular approach. The diagnosis, treatment, and prognosis of these tumors are reviewed.

Aberrant epigenetic regulation of bromodomain BRD4 in human colon cancer.

The bromodomain protein BRD4 is involved in cell proliferation and cell cycle progression, primarily through its role in acetylated chromatin-dependent regulation of transcription at targeted loci. Here, we show that BRD4 is frequently downregulated by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumors. Ectopic re-expression of BRD4 in these colon cancer cell lines markedly reduced in vivo tumor growth, suggesting a role of BRD4 in human colon cancer.

Pharmacological treatment of chronic pain - the need for CHANGE.

BACKGROUND: Although chronic pain affects around 20% of adults in Europe and the USA, there is substantial evidence that it is inadequately treated. In June 2009, an international group of pain specialists met in Brussels to identify the reasons for this and to achieve consensus on strategies for improving pain management. SCOPE: Literature on chronic pain management was reviewed, and information presented to and discussed by a panel of experts. FINDINGS: It was agreed that guidelines are not universally accepted by those involved in pain management, and pain treatment seems to be driven mainly by tradition and personal experience. Other factors include poor communication between patients and physicians, the side effects of analgesic drugs, and limited individualisation of therapy. Difficulty in maintaining the balance between adequate pain relief and acceptable tolerability, particularly with strong opioids, can lead to the establishment of a 'vicious circle' that alternates between lack of efficacy and unpleasant side effects, prompting discontinuation of treatment. The medical community's understanding of the physiological differences between nociceptive pain and neuropathic pain, which is often more severe and difficult to treat, could be improved. Increasing physicians' knowledge of the pharmacological options available to manage these different pain mechanisms offers the promise of better treatment decisions and more widespread adoption of a multi-mechanistic approach; this could involve loosely combining two substances from different drug classes, or administering an analgesic with two different mechanisms of action. In some circumstances, a single compound capable of addressing both nociceptive and neuropathic pain is desirable. CONCLUSIONS: To improve patient outcomes, a thorough understanding of pain mechanisms, sensitisation and multi-mechanistic management is required. Universal, user-friendly educational tools are therefore required to familiarise physicians with these topics, and also to improve communication between physicians and their pain patients, so that realistic expectations of treatment can be established.

[The role of sentinel lymph node biopsy in the diagnosis and prognosis of malignant melanoma]. / La biopsia del ganglio centinela: su papel diagnóstico y pronóstico en el melanoma maligno.

Sentinel lymph node biopsy was introduced into the management of cancer patients 20 years ago. Most hospitals now currently use the technique as a routine diagnostic tool in patients with localized malignant melanoma. However, the technique is complex and numerous details need to be determined and assessed to provide reliable diagnostic and prognostic information. In addition, the introduction of immunohistochemical and molecular techniques in the last decade has extended the information provided by the study of sentinel lymph nodes and created valuable opportunities for investigating the pathogenesis of this type of cancer. The aim of this review is to offer the reader a detailed analysis of the most important studies in the literature and the factors that should currently be considered in determining the indication for sentinel lymph node biopsy, performing the procedure correctly, and interpreting the findings in patients with malignant melanoma.

Papilomatose florida: tratamento pre-operatorio com metotrexate. / Florid papillomatosis: pre-operative treatment with methotrexate

Dois casos de papilomatose florida sao apresentados, um na face outro no pe ambos considerados inoperaveis a principio pela sua extensao. O uso de metotrexate em doses de 50 mg semanais via intramuscular durante 3 e 4 meses respectivamente, reduziu de forma tao notavel as massas tumorais que permitiu uma excelente recuperacao mediante cirurgia plastica e reparadora. O folow-up desta cura se estende neste momento a mais de dois anos em ambos os casos