Dysfunctional coping is related to impaired skin-related quality of life and psychological distress in patients with neurofibromatosis type 1 with major skin involvement.

BACKGROUND: Low skin-related quality of life (QoL) is usually associated with low levels of self-confidence and self-esteem and with high levels of anxiety and depression symptoms. The way patients cope with a physical disease impacts significantly on their psychosocial adjustment to the disorder and on their emotional functioning. OBJECTIVES: To explore how coping strategies, skin-related QoL, psychological distress and self-esteem interact in a sample of individuals with neurofibromatosis type 1 (NF1). METHODS: Seventy-two adult patients with NF1 completed the following questionnaires: Coping Orientation to Problem Experiences (COPE), Skindex-29, Padua Skin-Related QoL questionnaire (PSRQ), State-Trait Anxiety Inventory-X2 form (STAI-X2), Depression Questionnaire (DQ) and Rosenberg Self-Esteem Scale (RSES). The k-modes algorithm was used to identify clusters of patients based on four variables: sex, NF1 severity, number and distribution of cutaneous neurofibromas. Individuals in different clusters were compared with regard to their scores; correlations between scores were analysed within each cluster. RESULTS: Two main clusters were identified: individuals in Cluster 1 had a larger number and more widespread distribution of neurofibromas compared with Cluster 2. Patients in Cluster 1 scored higher only on several PSRQ and Skindex-29 scales. Among patients in Cluster 1, the COPE 'avoidance strategies' scale was significantly correlated with the PSRQ 'physical distress and impairments' scale, the Skindex-29 'physical symptoms' and 'functioning' scales, the STAI-X2, the DQ and the RSES. CONCLUSIONS: Patients with major skin involvement have reduced skin-related QoL. Among them, current findings tentatively suggest that the higher the use of dysfunctional coping, the more impaired are QoL, psychological distress and self-esteem. What's already known about this topic? Neurofibromatosis type 1 (NF1) can affect the quality of life (QoL) in adolescent and adult patients. Low skin-related QoL is usually associated with low levels of self-confidence and self-esteem and with high levels of anxiety and depression symptoms. Questionnaires evaluating skin-related QoL, anxiety, depression, self-esteem and coping are available. What does this study add? Patients with a large number and a widespread distribution of cutaneous neurofibromas have reduced skin-related QoL compared with patients with minor skin involvement. The newly developed Padua Skin-Related QoL questionnaire allows the simultaneous evaluation of discomfort and comfort skin-related QoL dimensions in patients with NF1. Among patients with major skin involvement, the higher the use of dysfunctional coping, the more impaired are skin-related QoL, psychological distress and self-esteem. Our data suggest that patients with NF1 with major skin involvement who endorse dysfunctional beliefs about their own coping abilities might benefit from psychological counselling and coping skills treatments aiming to both improve perceived self-efficacy and learn more adaptive coping strategies.

Serotonin transporter gene polymorphism in eating disorders: Data from a new biobank and META-analysis of previous studies.

UNLABELLED: Objectives Growing interest focuses on the association between 5-HTTLPR polymorphism and eating disorders (ED), but published findings have been conflicting. Methods The Italian BIO.VE.D.A. biobank provided 976 samples (735 ED patients and 241 controls) for genotyping. We conducted a literature search of studies published up to 1 April 2015, including studies reporting on 5HTTLPR genotype and allele frequencies in obesity and/or ED. We ran a meta-analysis, including data from BIO.VE.D.A. - comparing low and high-functioning genotype and allele frequencies in ED vs. CONTROLS: Results Data from 21 studies, plus BIO.VE.D.A., were extracted providing information from 3,736 patients and 2,707 controls. Neither low- nor high-functioning genotype frequencies in ED patients, with both bi- and tri-allelic models, differed from controls. Furthermore, neither low- nor high-functioning allele frequencies in ED or in BN, in both bi- and triallelic models, differed from control groups. After sensitivity analysis, results were the same in AN vs. CONTROLS: Results remained unaltered when investigating recessive and dominant models. Conclusions 5HTTLPR does not seem to be associated with ED in general, or with AN or BN in particular. Future studies in ED should explore the role of ethnicity and psychiatric comorbidity as a possible source of bias.

Pregnancy outcome in women exposed to leflunomide before or during pregnancy.

OBJECTIVE: Findings from animal studies have suggested that leflunomide may be a human teratogen. In the only human cohort study published to date, an increase in adverse outcomes in pregnancies after exposure to leflunomide was not detected. The aim of the present analysis was to expand on the previously published data with a description of birth outcomes among women who did not meet the previous cohort study criteria but who were exposed to leflunomide either during pregnancy or prior to conception. METHODS: Data on pregnancy exposures and outcomes were collected from 45 pregnant women who had contacted counseling services of the Organization of Teratology Information Specialists in the US or Canada between 1999 and 2009. Sixteen women were exposed to leflunomide during the first trimester of pregnancy and 29 women were exposed preconception. RESULTS: All 16 of the pregnancies with leflunomide exposure during pregnancy and 27 (93%) of the pregnancies with exposure prior to conception resulted in liveborn infants. There were 2 infants with major malformations from mothers who were exposed during pregnancy, and no malformations reported in the preconception group. There was a potential known alternative etiology for at least some of the defects observed. CONCLUSION: These data provide additional reassurance to women who inadvertently become pregnant while taking leflunomide and who undergo the washout procedure, as well as women who discontinue the medication prior to conception but have no prepregnancy documentation of drug clearance. However, until more conclusive data become available, women receiving leflunomide should be advised to use contraceptive methods and avoid pregnancy.

Dual intracellular pathways in gonadotropin releasing hormone (GNRH) induced desensitization of luteinizing hormone (LH) secretion.

The mechanisms of GnRH-induced desensitization of LH secretion are poorly understood. Protein kinase C (PKC) and protein kinase A (PKA) desensitize some receptors of the 7-membrane type, and the GnRH receptor has consensus phosphorylation sites for PKC in the first and third intracellular loops, and a site for PKA in the first intracellular loop. In the first set of experiments we determined whether synthetic peptides representing the three intracellular loops of the receptor could be phosphorylated in vitro by purified PKC and PKA. As compared with a model substrate peptide for PKC, the third intracellular loop was phosphorylated 74% and the first intracellular loop 21%; PKA-phosphorylated the first intracellular loop peptide 17% as well as a model peptide substrate. In the second set of experiments, we used phorbol 12-myristate 13 acetate (PMA), an established PKC stimulator, and cholera toxin (CTX), established to activate the Gs protein and presumed to activate PKA, to treat cultured rat pituitary cells followed by LH measurements. Treatment with both drugs severely impaired GnRH-stimulated LH secretion whereas neither drug alone reduced LH secretion. Dibutyryl cAMP did not duplicate the effects of cholera toxin suggesting that the CTX action could not be explained by an increase in cAMP. These results suggest that more than one intracellular signaling pathway requires activation in order to induce desensitization; one pathway involves PKC and the other involves a pathway stimulated by cholera toxin, presumably Gs protein, which does not involve PKA.

[POEMS syndrome]. / Síndrome de POEMS.

Poems syndrome is a rare multisystemic disorder. It manifestations are Polyneuropathy, Organomegaly, Endocrinopathy, and/or Edema, Monoclonal protein and changes in the Skin. (P.O.E.M.S.) Though some bibliography make no difference with osteoesclerotic myeloma it is considered a real syndrome. The polyneuropathy is customarily severe. Although high levels of immunoglobulins has been found in the poems, it has not been isolated a specific antibody that explain the polyneuropathy even though it is strongly suspected. The organomegaly, endocrinopathy, changes in the skin and other systems and involved organs could be in relationship to products secreted by plasmatic cells. We review the physiopathology and bibliography of the Poems, especially its neurological expression its nosologic location different from osteosclerotic myeloma and a possible relationship to the Herpes Virus 8. It was crossed in Medline the terms P.O.E.M.S. and syndrome and were obtained 271 abstracts that were all examined and finally selected the bibliography considerate meaningful for the objectives. It is presented briefly a case. P.O.E.M.S. is a syndrome that is associated to multiple plasma cell dyscracia, included the osteoesclerotic myeloma. Prognosis and the treatment vary with the underlying disease. As physiopathology of this syndrome is insinuated the action of the interleukins 1-beta (IL-1 beta) and 6 (IL-6), the vascular growth endothelial factor (VGEF), the tumoral necrosis factor alpha (TNF-alpha) and antibodies anti-nerve. The P.O.E.M.S. is a syndrome with own identity. The Herpes Virus 8 may plays a key rol to uncover the Poems physiopathology.

Síndrome de POEMS. / [POEMS syndrome]

Poems syndrome is a rare multisystemic disorder. It manifestations are Polyneuropathy, Organomegaly, Endocrinopathy, and/or Edema, Monoclonal protein and changes in the Skin. (P.O.E.M.S.) Though some bibliography make no difference with osteoesclerotic myeloma it is considered a real syndrome. The polyneuropathy is customarily severe. Although high levels of immunoglobulins has been found in the poems, it has not been isolated a specific antibody that explain the polyneuropathy even though it is strongly suspected. The organomegaly, endocrinopathy, changes in the skin and other systems and involved organs could be in relationship to products secreted by plasmatic cells. We review the physiopathology and bibliography of the Poems, especially its neurological expression its nosologic location different from osteosclerotic myeloma and a possible relationship to the Herpes Virus 8. It was crossed in Medline the terms P.O.E.M.S. and syndrome and were obtained 271 abstracts that were all examined and finally selected the bibliography considerate meaningful for the objectives. It is presented briefly a case. P.O.E.M.S. is a syndrome that is associated to multiple plasma cell dyscracia, included the osteoesclerotic myeloma. Prognosis and the treatment vary with the underlying disease. As physiopathology of this syndrome is insinuated the action of the interleukins 1-beta (IL-1 beta) and 6 (IL-6), the vascular growth endothelial factor (VGEF), the tumoral necrosis factor alpha (TNF-alpha) and antibodies anti-nerve. The P.O.E.M.S. is a syndrome with own identity. The Herpes Virus 8 may plays a key rol to uncover the Poems physiopathology.

A temporally intermediate mode of gonadotropin releasing hormone-induced desensitization of luteinizing hormone secretion.

The classical mode of luteinizing hormone (LH) secretory desensitization in the rat appears after 3-6 h of continuous in vitro administration of gonadotropin (GnRH). A second mode has been reported to occur very rapidly (< 2 min) after the onset of GnRH administration, and to reverse within 3 min after its withdrawal. Here, the existence of a third mode of desensitization is reported. occurring at 40-50 min after initiation of continuous GnRH administration. Rat pituitary cells were perifused with 10(-8) M GnRH for 6 h: 10 min samples were collected for LH measurements by radioimmunoassay. As expected, the pattern of LH release was biphasic: LH levels peaked in the first phase at 30 min, decreased at 40-50 min, increased in the second phase to maximal levels at 90-110 min, and then decreased in the classical desensitization mode to near-baseline values by 300-360 min. Static incubations of pituitary cells in Petri dishes in the presence of high (10(-8) M) or submaximal (10(-9) M) GnRH concentrations confirmed the decrease in LH secretion at 40-50 min. Measurement of LH by reverse hemolytic plaque assay (RHPA) confirmed the existence of this new mode of desensitization; since 93% of all gonadotropes had become secretory at 40-50 min, the possibility of two subpopulations of gonadotropes accounting for the two phases of LH secretion appears to be ruled-out. GnRH receptor binding studies demonstrated a approximately 50% decrease in cell-surface binding in association with the desensitization at 40-50 min. These studies suggest the existence of a third mode of GnRH-induced LH secretory desensitization that is not due to gonadotrope subpopulations but may be causally associated with decreased GnRH receptor binding.

Gonadotropin-releasing hormone-induced desensitization may account for the decrease in pituitary responsiveness after the preovulatory luteinizing hormone surge.

The LH secretory response of gonadotropes to GnRH varies during the estrous cycle of the rat. The increased secretion of estrogens during the 24-48 h before the preovulatory surge of LH secretion and the enhanced quantities of progesterone secreted acutely during the surge elevate the responsiveness of hypophysial gonadotropes to GnRH. However, the cause of the massive decline in GnRH responsiveness that occurs during or after the surge remains unknown. In the present studies, we investigated the possibility that it is due to GnRH-induced desensitization of gonadotropes. Dispersed pituitary cells from proestrous and estrous rats were preincubated with GnRH (3 or 6 h, 10(- 10) or 10(-9) M), progesterone (13 h, 100 or 200 nM), GnRH plus progesterone, or medium alone. Then, the cells were retrypsinized to permit performance of the reverse hemolytic plaque assay for measurement of LH secretin, during which they were treated with GnRH(0,10(-11),10(-10), and 10(-8)M) for 2 h. The cells from estrous animals showed the large decline in GnRH responsiveness typical of that day of the cycle compared to those from proestrous animals (the total amount of LH secreted decreased by 50-70%). Preincubation of cells from proestrous rat pituitary glands with GnRH in concentrations and for durations that were designed to mimic the physiological situation induced a decline in GnRH responsiveness similar to that observed at estrus. Preincubation with progesterone also reduced the pituitary responsiveness to GnRH in a dose-dependent manner, but did not show additive effects with GnRH. Our results suggest that the major increase in GnRH secretion that induces the preovulatory surge of LH secretion may also participate in inducing the major decrease in pituitary responsiveness to GnRH that occurs from proestrus to estrus.