Clinical Spectrum of Capillary Malformation–Arteriovenous Malformation Syndrome Presenting to a Pediatric Dermatology Practice: A Retrospective Study

Capillary malformation–arteriovenous malformation syndrome (CM‐AVM) is an autosomal dominant disorder caused by RASA1 mutations. The prevalence and phenotypic spectrum are unknown. Evaluation of patients with multiple CMs is challenging because associated AVMs can be life threatening. The objective of this study was to describe the clinical characteristics of children presenting with features of CM‐AVM to an academic pediatric dermatology practice. After institutional review board approval was received, a retrospective chart review was performed of patients presenting between 2009 and 2012 with features of CM‐AVM. We report nine cases. Presenting symptoms ranged from extensive vascular stains and cardiac failure to CMs noted incidentally during routine skin examination. All demonstrated multiple CMs, two had Parkes Weber syndrome, and two had multiple infantile hemangiomas. Seven patients had family histories of multiple CMs; three had family histories of large, atypical CMs. Six had personal or family histories of AVMs. Genetic evaluation was recommended for all and was pursued by six families; four RASA1 mutations were identified, including one de novo. Consultations with neurology, cardiology, and orthopedics were recommended. Most patients (89%) have not required treatment to date. CM‐AVM is an underrecognized condition with a wide clinical spectrum that often presents in childhood. Further evaluation may be indicated in patients with multiple CMs. This study is limited by its small and retrospective nature.     

The Course of Eating Disorders Involving Bingeing and Purging Among Adolescent Girls: Prevalence,Stability, and Transitions

Purpose

To quantify eating disorder (ED) stability and diagnostic transition among a community-based sample of adolescents and young adult females in the United States.

Hypoactive sexual desire disorder in postmenopausal women.

Decreases in sex hormone levels with menopause may bring about a number of consequences in women's general health and sexual well-being, especially when levels decline suddenly and prematurely, as in surgical menopause. In addition to the well-established role of estrogens in preserving the biological basis of sexual response, there is emerging evidence that androgens are significant independent determinants affecting sexual desire, activity and satisfaction, as well as mood, energy and other components of women's health. Hypoactive sexual desire disorder (HSDD), a persistent absence of sexual fantasies or thoughts and/or desire for and receptivity to sexual activity that causes personal distress, is experienced by some postmenopausal women. Even though conventional hormone therapy with estrogens or estrogens and progestogens may be effective for vaginal atrophy, increasing vaginal lubrication and reducing dyspareunia, it has not been shown to consistently increase sexual desire or activity and many women with sexual dysfunction remain unresponsive. Several recent, large, phase III studies have shown that the addition of transdermal testosterone to conventional hormone therapy can be helpful in surgically menopausal women presenting with HSDD. After 24 weeks of treatment in these studies, testosterone-treated women experienced significantly greater increases in satisfying sexual activity and sexual desire, and greater decreases in distress, than placebo-treated women. Accurate clinical assessment and individualized management of sexual symptoms are fundamentally important for all menopausal women with HSDD or other sexual problems.     

Notions of child health: mothers' accounts of health in their young babies

This paper is concerned with mothers’ understandings of child health in their young babies. To explore how child health is depicted, explained and contextualised by mothers, altogether 29 mothers in Stockholm and London were interviewed through the baby's first months about day-to-day experiences of the baby's health and well-being. The analysis of the mothers’ accounts reveals how the mothers, in the process of assessing health, try to ‘read’ the bodily signs and reactions in their babies. Some major themes emerge on how the mothers identify and characterise threats to the health of the baby; here described as threats of abnormalities, threats to the survival of the baby, threats to the thriving of the baby and threats from illnesses. Notions of child health are discussed in relation to the ‘bodily’ and the ‘social’, and how the embodied images of child health are intertwined with the mothers’ presentations of themselves as responsible for the health of their children and as ‘worthy’ parents.     

Effect of selected fluorinated drugs in a "ringing" gel on rheological behaviour and skin permeation.

The purpose of the present study was to investigate the influence of different drugs exhibiting different solubility on the viscoelastic properties and on the skin diffusion profile of a ringing gel. In a preliminary rheology study with the placebo gel predominating elastic properties were confirmed and a temperature influence was indicated. Fluconazole, fludrocortisone-acetate, flumethasone-pivalate, flutamide and flufenamic-acid each 1% (w/w) were incorporated into the preparation and oscillatory measurements were performed at temperatures of 25, 28, 32 and 37 degrees C. In all drug containing formulations a high elastic G' value predominated the viscous G' value. The highest G' value could be obtained with the incorporated flumethasone-pivalate. Additionally in almost all cases the G' values decreased with increasing temperature compared to the placebo gel. Additionally in vitro standard diffusion experiments using Franz-type cells and porcine skin were performed. Following rank order of the cumulative drug release after 48 h was obtained: fluconazole>flufenamic-acid>flumethasone-pivalate>flutamide>fludrocortisone-acetate. Furthermore an excellent chemical stability of all incorporated drugs was confirmed over 10 weeks.     

Dysphoric Rumination Impairs Concentration on Academic Tasks

Three studies investigated the effects of dysphoric rumination on concentration during 3 academic tasks—reading a passage from the GRE (Study 1), watching a videotaped lecture (Study 2), and proofreading written text (Study 3). Before performing these tasks, dysphoric and nondysphoric students were induced either to ruminate about themselves or to distract themselves by focusing on neutral images (all three studies) or by planning an event (Study 1). The results supported our hypothesis that dysphoric rumination, relative to distraction, would impair students' concentration. In all 3 studies, dysphoric ruminators reported difficulty concentrating, as well as interfering thoughts, during the relevant academic tasks. Furthermore, dysphoric ruminators were slower than dysphoric distractors in completing the tasks—specifically, reading the GRE passage (Study 1) and answering lecture comprehension questions (Study 2). In addition, dysphoric participants who ruminated showed impaired reading strategies (Study 1), reduced comprehension of academic material (Study 2), and poor proofreading performance (Study 3). These findings suggest that, in addition to its documented adverse effects on mood, thinking, and problem-solving, self-focused rumination interferes with instrumental behavior. Implications for social relationships and job performance are discussed.     

Biochemical studies of stimulus convergence during classical conditioning in Aplysia: dual regulation of adenylate cyclase by Ca2+/calmodulin and transmitter.

Activity-dependent facilitation is a mechanism of associative synaptic plasticity that contributes to classical conditioning in Aplysia. Previous studies of activity-dependent facilitation in the mechanosensory neurons of Aplysia suggested that the Ca2+ influx during paired spike activity enhances the transmitter-stimulated, cAMP-dependent, presynaptic facilitation in these cells. Moreover, paired activity was found to potentiate the activation of the adenylate cyclase by transmitter. It was therefore proposed that the Ca2+/calmodulin-sensitive cyclase may serve as a site of interaction between the inputs from the conditioned and unconditioned stimuli. These studies were carried out to test whether a Ca2+/calmodulin-sensitive adenylate cyclase in the Aplysia CNS has the properties necessary to mediate such an associative interaction. Three lines of evidence indicate that the same cyclase molecules that are sensitive to Ca2+/calmodulin are also stimulated by receptor to facilitatory transmitter via the stimulatory G-protein, Gs: First, calmodulin inhibitors reduced stimulation of the cyclase by facilitatory transmitter. When membranes had been preexposed to one of these inhibitors, trifluoperazine, the addition of exogenous calmodulin partially reversed the inhibition. Second, when Gs had been activated by GTP gamma S, so that it persistently activated the catalytic unit of the cyclase, stimulation of the cyclase by Ca2+ was greatly amplified, suggesting that the two inputs interact in activating a common population of the enzyme. Third, solubilized cyclase activity that bound to calmodulin-Sepharose in a Ca(2+)-dependent manner was stimulated by Gs, which had been partially purified from Aplysia CNS, as well as by Ca2+/calmodulin. Having demonstrated dual activation of the cyclase, we have explored the dependence of cyclase activation on the temporal pattern of Ca2+ and transmitter addition. Optimal activation required that a pulse of Ca2+ temporally overlap the addition of facilitatory transmitter. These several results suggested that the dually regulated adenylate cyclase might underlie the temporal requirements for effective classical conditioning in this system.     

Syntactic language processing: ERP lesion data on the role of the basal ganglia.

The role of the basal ganglia in syntactic language processing was investigated with event-related brain potentials in fourteen neurologically impaired patients. Seven of these patients had basal ganglia lesions while 7 other patients primarily had lesions of the left temporo-parietal region excluding the basal ganglia. All patients listened to sentences that were either correct or included a verb argument structure violation. In previous experiments this type of violation elicited a biphasic pattern of an N400-P600 complex in young healthy participants. While the N400 may result from incorrect semantic-thematic role assignment, the P600 reflects the fact that verb information does not license the syntactic structure at present. Results of the patient experiment revealed a double dissociation: patients with left temporo-parietal lesions only show a P600, whereas patients with lesions of the basal ganglia showed no P600, but a negativity with extended duration that resembled an N400. The latter pattern not only confirms previous reports that the basal ganglia modulate the P600 but extends these results by showing that the N400 as a late semantic-thematic integration process appears partially modulated by the basal ganglia.     

Nonparasitic Cysts of the Liver: Results and Options of Surgical Treatment

n = 9) should be regarded as a palliative measure. Within a short period, CT-guided aspiration led to recurrence of symptoms in seven of our patients. Standard treatment of NPHC is fenestration with widest possible excision of the cystic wall, which can be performed laparoscopically ( n = 10) or by the conventional surgical mode ( n = 54). One patient was initially operated by the laparoscopic technique but developed bleeding, which necessitated conversion to the open mode. Three patients underwent synchronous laparoscopic cholecystectomy. Recurrence rates were similar: 11% in the laparoscopically treated group and 13% in the group that underwent conventional open surgery. Conventional surgical treatment was always successful in cases of solitary cysts. However, in cases of multiple cysts measuring more than 5 cm, conventional surgery was followed by recurrence of symptoms in 26% of patients (7/27), who then had to undergo a second operation. Partial resection of the liver ( n = 9) was successfully performed in cases of polycystic disease ( n = 5) with concomitant enlargement of the organ as well as in cases of large solitary cysts of the left lobe of the liver ( n = 4). In patients in whom we found that the cysts communicated with the ductal system ( n = 3), we performed a cystojejunostomy to drain the bile. The complication rate was low. In addition to frequent postoperative ascites, which necessitated no further intervention, we observed infectious complications in four patients. Twenty patients (22%) expired during a mean follow-up period of 6.2 years. Interestingly, deaths were frequently associated with malignancy (11/20). After fenestration of multiple cysts measuring > 5 cm, the patients are at high risk for recurrence. Hence partial resection of the liver is an excellent therapeutic alternative in selected patients with polycystic disease and massive enlargement of the organ in whom the disease could not be controlled by simple fenestration. The results of this study show that laparoscopic fenestration should replace the conventional surgical technique as the gold standard in cases of NPHC because the laparoscopic technique is less stressful for the patient and is associated with a rate of success similar to that of the conventional technique.     

Clinical impact of CCM mutation detection in familial cavernous angioma

Introduction and background A 3-year-old Bosnian girl with a large symptomatic brainstem and multiple supratentorial cavernous angiomas, who underwent neurosurgical treatment, is presented. As multiple cavernomas are more common in familial cases, genetic analyses and neuroradiological imaging were performed in the patient and her parents to see whether there was any evidence for inheritance. This information is important for genetic counseling and provision of medical care for at-risk relatives. Currently, no recommendation is available on how to manage these cases.Results Genetic analyses demonstrated a novel CCM1 frameshift mutation (c.1683_1684insA; p.V562SfsX6) in the child and the asymptomatic 27-year-old mother. Sensitive gradient-echo magnetic resonance imaging of the mother revealed multiple supratentorial lesions, whereas analogous imaging of the father showed no pathological findings.Conclusion This case exemplifies that seemingly sporadic cases with multiple lesions might well be hereditary and that presymptomatic genetic testing of family members may identify relatives for whom clinical and neuroradiological monitoring is indicated.