A contingency-based approach to the etiology of 'disorganized' attachment: the 'flickering switch' hypothesis

The authors present a new approach to the etiology of disorganized attachment based on contingency detection theory. According to this view, the relevant common factor in parental maltreatment and unresolved loss that leads to disorganized attachment has to do with the type of "deviant contingency environment" that both of these conditions generate. In such environments, infants experience periods of being in control followed by periods of sudden loss of control over the caregiver's behavior. The authors hypothesize that this adversely affects the developmental unfolding of the infant's innate "contingency detection module" (Gergely & Watson, 1999), which normally involves a maturational shift around 3 months from an initial attention bias for perfectly contingent stimulation to an emerging preference for less-than-perfect social contingencies. The periodically changing controllability of abusive and dissociating "unresolved" attachment figures is hypothesized to block this process and to lead to the defensive fixation of a dysfunctional "flickering contingency switch" mechanism with two dominant and competing target positions (self-oriented vs. other-oriented). This results in the dissociative style of attention and behavioral organization characteristic of disorganized infant attachment. The authors summarize the preliminary results of an empirical study that provides support for this model in 6.5-month-old infants using a modified Still-Face situation (the Mirror Interaction Situation). The study demonstrates differential emotional and behavioral reactions to sudden loss of maternal contingency and a specific interest in exploring the perfectly contingent self-image in the mirror in infants who at 12 months become categorized as "disorganized" in the Strange Situation.     

The obscure object of desire: 'nearly, but clearly not, like me': contingency preference in normal children versus children with autism

The author describes the central role of contingency detection in early socioemotional development. It has been proposed (Gergely & Watson, 1999) that infants are innately equipped with a complex perceptual mechanism, the "contingency detection module," which functions to establish the primary representation of the bodily self as well as the later orientation toward reactive social objects. According to the "contingency switch" model, the target value of the module that is initially genetically set to preferentially explore perfectly response-contingent stimulation is "switched" at around 3 months toward a preference for less-than-perfect social contingencies. It is hypothesized that the primary cause of childhood autism is a genetic defect, due to which the normal process of switching contingency preference at around 3 months does not take place. Preliminary results from an experimental study to test this model are reported. The study contrasts the preferential reactions of normal children and children with autism to perfect versus imitative (high-but-imperfect) contingencies. The results provide support for the contingency switch hypothesis of the etiology of childhood autism.     

Chronic pericarditis in Hodgkin disease

INTRODUCTION: Among late complications of Hodgkin's disease's treatment the cardiovascular complications are important. The incidence of the late onset (later than 48 months) of chronic pericardial disease is from 11 to 50% among patients with Hodgkin's disease with irradiation in the past history. PURPOSE AND METHODS: Authors are presenting chronic constrictive pericarditis in a case among late consequences of therapy of Hodgkin's disease. It's difficult to observe and treat, because it's a rarity. RESULTS (CASE REPORT): A male patient, who is 35 year old in the present, developed III/A2 clinical stage, mixed cellularity Hodgkin's disease in 1992. He got combined chemotherapy and irradiation repeated and he came to complete remission. In 1999 he had no symptoms, but the physical examination, routine chest radiography and echocardiography proved pericardial effusion. Apart from the most frequent reasons of pericarditis and pericardial effusion, radiation induced, hypothyroid and primary manifestation of Hodgkin's disease equally arised. After repeated fenestration of the pericardium partial pericardiectomy was necessary. Chronic constrictive pericarditis was proved by the histological evaluation of the pericardial tissue that was probably provoked by the mediastinal irradiation. Since the pericardiectomy he has being well, he had no relapsed and no signs of pericardial fluid was observed. CONCLUSIONS: The early recognition and treatment of late complications are possible by the help of the patient's follow-up. These complications of Hodgkin's disease with using of modern radiotherapy apparatus are usually avoided.     

Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: A nationwide study in Hungary

We conducted a nationwide, full-population based investigation to evaluate the comparative effectiveness of all marketed second generation antipsychotic drugs (SGA) prescribed for outpatients with the diagnosis of schizophrenia in Hungary. Using the national central register, our observational follow-up study included all patients with schizophrenia or related disorder between 01/01/2006 and 30/06/2008. The study cohort comprised 9567 patients who started new SGA during the inclusion period (01/07/2007–30/06/2008). All-cause medication discontinuation of 8 SGAs (1 depot and 7 oral formulations) marketed during the inclusion period, and the time to all-cause discontinuation were the main outcomes. Statistical models included the Kaplan–Meier and the Cox proportional hazards models with propensity score adjustment. Patients treated with a depot formulation risperidone had the longest time to discontinuation with a median of 215 days (95%CI:181–242 days), which was statistically significantly different compared to patients treated with the rest of the medications: olanzapine (136 days, 95%CI:121–153 days), aripiprazole (102 days, 95%CI:81–126 days), ziprasidone (93 days, 95%CI:82–119 days), quetiapine (89 days, 95%CI:81–100 days), clozapine (76 days, 95%CI:54–92 days), amisulpride (73 days, 95%CI:62–85 days), and risperidone (55 days, 95%CI: 41–63 days). Our results in Hungary are partly similar to those of a recent register-based study in Finland with patients who were discharged from their first hospitalization for schizophrenia (Tiihonen et al., 2006, Tiihonen et al., 2011); namely the median times to all-cause medication discontinuation were <120 days for the majority of the oral SGA. In terms of medication differences, our data support the superior effectiveness of the depot formulation regarding all-cause discontinuation, followed by olanzapine at the efficacy rank order.     

The role of dental evaluation and cephalometric analysis in the diagnosis of Williams–Beuren syndrome

Summary Williams–Beuren syndrome (WS) is a genetic condition with an incidence of 1 in 20,000–50,000 live births. The syndrome consists of supravalvular aortic stenosis, characteristic dysmorphic facial features named elf face and intellectual disability. Early diagnosis of the syndrome is important since many of its features require treatment, and the prognosis can be dramatically improved by early recognition and management. This developmental disorder is well known to be clinically heterogeneous, making diagnosis difficult if based on the clinical picture. However, genetic testing is expensive and it is not cost-effective to screen all patients based on clinical suspicion. Our goal was to develop a novel clinical screening method that would be sensitive, specific, inexpensive and readily available. We performed cephalometric analysis and dental evaluation of 33 patients with genetically proven WS. Cephalometric analysis of soft tissues showed that with normal SNA, SNB and ANB angles, the lips were in front of the line of harmony. This finding was present in all WS patients (n = 33) but in none of the age-matched controls (n = 100). No other differences were found between WS and control patients. This cephalometric finding is specific and sensitive for WS and can be used in the diagnostic procedure, whereas none of the conventional dental evaluations are useful.     

Hitting the brakes: targeting microtubule motors in cancer

Despite the growing number of therapies that target cancer-specific pathways, cytotoxic treatments remain important clinical tools. The rationale for targeting cell proliferation by chemotherapeutic agents stems from the assumption that tumours harbour a greater fraction of actively dividing cells than normal tissues. One such group of cytotoxic drugs impair microtubule polymers, which are cytoskeletal components of cells essential for many processes including mitosis. However, in addition to their antimitotic action, these agents cause debilitating and dose-limiting neurotoxicity because of the essential functions of microtubules in neurons. To overcome this limitation, drugs against mitosis-specific targets have been developed over the past decade, albeit with variable clinical success. Here we review the key lessons learnt from antimitotic therapies with a focus on inhibitors of microtubule motor proteins. Furthermore, based on the cancer genome data, we describe a number of motor proteins with tumour type-specific alterations, which warrant further investigation in the quest for cytotoxic targets with increased cancer specificity.