Gender paradox in cardiac calcium deposits in middle-aged and elderly patients: mitral annular and coronary calcifications interrelationship

OBJECTIVES: mitral annular calcification (MAC) occurs mainly in middle-aged and elderly patients and can lead to serious clinical consequences. Male predominance in the prevalence of coronary disease is well-established. Paradoxically, the prevalence of MAC, which is theoretically based on the same etiological mechanisms as coronary atherosclerosis, seems to be predominant in postmenopausal women. The goal of this work was to investigate gender influences on interrelationship between MAC and coronary calcifications (CC) in the same population of middle-aged and elderly patients with increased cardiovascular risk. METHODS: the study comprised 522 patients (284 men and 238 postmenopausal women, aged 52-80 years, mean 65+/-6), who were recruited to the International Nifedipine GITS Study of Intervention as a Goal in Hypertension Treatment (INSIGHT) study in our region. They underwent both fast spiral computed tomography of the heart and echo-Doppler. MAC was defined as advanced when its thickness was > or =5mm; otherwise it was defined as trivial. RESULTS: there were 37 (16%) women and 25 (9%) men with advanced MAC (AMAC), 97 (41%) women and 118 (42%) men with trivial MAC and 104 (44%) women and 141 (50%) men without MAC. The prevalence of any type of CC was significantly higher among men (P=0. 001). In sharp contrast to the distinct male predominance in coronary disease, AMAC was more prevalent among women. In patients without CC prevalence was 9 and 4%, increasing to 16 and 8% in those with nonsevere CC and to 38 and 14% in patients with severe CC, respectively (P=0.001). Multivariate analysis showed that AMAC can predict the presence of severe CC in women and men, with OR of 4.1 and 2.6 (CI 1.2-14.8 and 1.0-10.6) and coronary disease with OR of 2. 5 and 2.5 (CI 0.6-10.6 and 1.0-6.4), respectively. CONCLUSIONS: AMAC signifies a high probability of coronary atherosclerosis in patients of both genders. The inverted gender predominance in the prevalence of annular calcification and CC could be explained by additional etiological (likely osteoporotic) mechanisms of MAC development among postmenopausal women.     

EEG findings and language patterns in autistic children: clinical correlations

Several authors have used the EEG as a diagnostic tool to identify distinctive patterns of cerebral dysfunction in autistic children. However, evidence is needed to support the hypothesis that their level of functioning correlates with their EEG profile. In this study EEG's were obtained in 17 autistic children without sedation and following sleep deprivation. These children were also evaluated in a double blind procedure with regard to their speech and communication abilities. We did not find a statistically significant correlation between EEG changes and speech performance. None of the autistic children using an augmentative system of communication had any EEG abnormalities. However, a normal EEG is not sufficient to predict successful response to communication therapy. Since the effect of sedative drugs on brain electrical activity limits the value of tracings, we recommend the sleep deprivation techniques when "difficult" children have to undergo EEG testing. Parents' or guardians' participation during the procedure is encouraged.     

International consensus statement on attention-deficit/hyperactivity disorder (ADHD) and disruptive behaviour disorders (DBDs): clinical implications and treatment practice suggestions.

Researchers and clinicians worldwide share concerns that many youngsters with attention-deficit/hyperactivity disorder (ADHD) and/or disruptive behaviour disorders (DBDs) do not receive appropriate treatment despite availability of effective therapies. At the request of Johnson and Johnson (sponsor), 11 international experts in child and adolescent psychiatry were selected by Professor Stan Kutcher (chair) to address these concerns. This paper describes the experts' consensus conclusions, including treatment practice suggestions for physicians involved in the early treatment of youngsters with ADHD (or hyperkinetic disorder, in countries preferring this classification) and/or DBDs internationally: suggested first-line treatment for ADHD without comorbidity is psychostimulant medication aided by psychosocial intervention. For ADHD with comorbid conduct disorder (CD), psychosocial intervention combined with pharmacotherapy is suggested. For primary CD, suggested first-line treatment is psychosocial intervention, with pharmacotherapy considered as an 'add-on' when aggression/impulsivity is marked and persistent. Pharmacotherapy requires careful titration; full-day coverage is the suggested goal. Regular long-term follow-up is recommended.     

Type II antithrombin deficiency caused by a large in‐frame insertion: structural,functional and pathological relevance

Summary. Background: The metastable native conformation of serpins is required for their protease inhibition mechanism, but also renders them vulnerable to missense mutations that promote protein misfolding with pathological consequences. Objective: To characterize the first antithrombin deficiency caused by a large in‐frame insertion. Patients/Methods: Functional, biochemical and molecular analysis of the proband and relatives was performed. Recombinant antithrombin was expressed in HEK‐EBNA cells. Plasma and recombinant antithrombins were purified and sequenced by Edman degradation. The stability was evaluated by calorimetry. Reactive centre loop (RCL) exposure was determined by thrombin cleavage. Mutant antithrombin was crystallized as a dimer with latent plasma antithrombin. Results: The patient, with a spontaneous pulmonary embolism, belongs to a family with significant thrombotic history. We identified a complex heterozygous in‐frame insertion of 24 bp in SERPINC1, affecting strand 3 of β‐sheet A, a region highly conserved in serpins. Surprisingly, the insertion resulted in a type II antithrombin deficiency with heparin binding defect. The mutant antithrombin, with a molecular weight of 59 kDa, had a proteolytic cleavage at W49 but maintained the N‐terminal disulphide bonds, and was conformationally sensitive. The variant was non‐inhibitory. Analysis of the crystal structure of the hyperstable recombinant protein showed that the inserted sequence annealed into β‐sheet A as the fourth strand, and maintained a native RCL. Conclusions: This is the first case of a large in frame‐insertion that allows correct folding, glycosylation, and secretion of a serpin, resulting in a conformationally sensitive non‐inhibitory variant, which acquires a hyperstable conformation with a native RCL.     

Acute surgical unit safely reduces unnecessary after-hours cholecystectomy

Introduction

The acute surgical model has been trialled in several institutions with mixed results. The aim of this study was to determine whether the acute surgical model provides better outcomes for patients with acute biliary presentation, compared with the traditional emergency surgery model of care.

Methods

A retrospective review was carried out of patients who were admitted for management of acute biliary presentation, before and after the establishment of an acute surgical unit (ASU). Outcomes measured were time to operation, operating time, after-hours operation (6pm – 8am), length of stay and surgical complications.

Results

A total of 342 patients presented with acute biliary symptoms and were managed operatively. The median time to operation was significantly reduced in the ASU group (32.4 vs 25.4 hours, p=0.047), as were the proportion of operations performed after hours (19.5% vs 2.5%, p<0.001) and the median length of stay (4 vs 3 days, p<0.001). The median operating time, rate of conversion to open cholecystectomy and wound infection rates remained similar.

Conclusions

Implementation of an ASU can lead to objective differences in outcomes for patients who present with acute cholecystitis. In our study, the ASU significantly reduced time to operation, the number of operations performed after hours and length of stay.