Role of core needle biopsy in the treatment of radial scar

Invasive tumor or ductal carcinoma in situ occur in radial sclerosing lesions in one third of the cases therefore, surgical excision is mandatory. Forty-five patients with radial scar morphology were examined. Ultrasound guided fine-needle aspiration biopsy (FNAB) and core biopsy (CB) were performed in all cases. The postoperative pathological findings were compared to the results of preoperative biopsies. Sensitivity of preoperative percutaneous biopsies (FNAB and CB) was 17.6% and 70.6%, false-negative rate was 82.4% with FNAB and 29.4% with CB. The negative predictive value was 48.1% and 84.8% respectively. Had we done preoperative cytology only, we would have had to perform a two-step procedure (sentinel lymph node biopsy) in 7 patients (15.6%), while with preoperative core biopsy it has decreased to 2 patients (4.4%). Preoperative CB in small radial stellate lesions is recommended to achieve accurate diagnosis in order to avoid a two-step surgical procedures.     

Serum chromogranin A concentration and intradialytic hypotension in chronic haemodialysis patients

Aim The aim of this study was to investigate the influence of haemodialysis on plasma chromogranin A (CgA) concentration and to assess the relationship between CgA, blood pressure, occurrence of intradialytic hypotension episodes and residual renal function, respectively. Methods The study included 38 chronic haemodialysis patients (24 M, 14 F; mean age 56.2 ± 13.6 years). Plasma CgA and blood pressure were measured before and after a mid-week dialysis. Control group included 10 age- and sex-matched healthy subjects. Results Plasma CgA levels were on average 50-fold higher in HD patients than in the controls (699 ± 138 vs. 14 ± 6 U/L). In HD patients plasma CgA corrected for ultrafiltration rates significantly increased (to 836 ± 214 U/L, P < 0.001) at the end of dialysis procedure. In patients with (n = 8) and without frequent symptomatic intradialytic hypotension episodes predialysis values of CgA were similar (701 ± 169 vs. 698 ± 132 U/L) but post-dialysis were significantly lower in the former group (746 ± 312 vs. 860 ± 177 U/L; P = 0.03) despite a similar rate of ultrafiltration (2675 ± 1009 and 2583 ± 1311 ml, respectively). Accordingly, in patients with intradialytic hypotension an increase of plasma CgA during dialysis was also much lower than in patients without hypotension (45 ± 81 vs. 163 ± 144 U/L; P = 0.001). Conclusions CgA undergoes marked accumulation in renal failure. The increase of plasma CgA during dialysis is impaired in subjects with intradialytic hypotension episodes, which confirms the role of autonomic dysfunction in the pathogenesis of this complication.     

The chondrocyte channelome: A narrative review

Chondrocytes are the main cells in the extracellular matrix (ECM) of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function. It includes channels, transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and ECM proteins and other macromolecular complexes. The chondrocyte channelome is a sub-compartment of the membranome and includes a complete set of ion channels and porins expressed in these cells. Many of these are multi-functional proteins with “moonlighting” roles, serving as channels, receptors and signalling components of larger molecular assemblies. The aim of this review is to summarise our current knowledge of the fundamental aspects of the chondrocyte channelome, discuss its relevance to cartilage biology and highlight its possible role in the pathogenesis of osteoarthritis (OA). Excessive and inappropriate mechanical loads, an inflammatory micro-environment, alternative splicing of channel components or accumulation of basic calcium phosphate crystals can result in an altered chondrocyte channelome impairing its function. Alterations in Ca²⁺ signalling may lead to defective synthesis of ECM macromolecules and aggravated catabolic responses in chondrocytes, which is an important and relatively unexplored aspect of the complex and poorly understood mechanism of OA development.     

Three-year follow-up of children with open-set speech recognition who use the MED-EL cochlear implant system

Improvement in implant technology and the fact that children with cochlear implants have surpassed all expectations have led the field to believe that open-set speech understanding is a common and expected outcome. The available literature suggests this to be the case in open-set word understanding. This study shows the results of 41 pre-lingually deafened children with a minimum of 3 years' cochlear implant experience assessed on the EARS test battery, which includes open-set phoneme, word and sentence tests. Results show that some open-set skills emerge by 6 months after implantation. There was significant improvement over time, even after 3 years of cochlear implant experience. A significant effect of age at implantation was also demonstrated. Results suggest that cochlear-implanted children develop open-set speech recognition soon after implantation, and these skills develop over a long period of time, highlighting the need for continued therapy to maximize listening and learning.     

Early onset Alzheimer's disease is associated with a distinct neuropsychological profile

Alzheimer's disease (AD) in younger patients is associated with a higher prevalence of atypical symptoms. We examined neuropsychological performance according to age-at-onset. We assessed cognition in 172 patients with AD (81 early and 91 late onset) in five cognitive domains (memory, language, visuo-spatial functioning, executive functioning, attention). Dementia severity was assessed using the Mini-Mental State Examination (MMSE) and global cognitive decline using Cambridge Cognitive Examination (CAMCOG). Analyses of variance were performed with age-at-onset as between-subjects factor, and gender and education as covariates. Analysis was repeated after stratification for dementia severity (based on median MMSE). In early onset AD, age (mean ± SD) was 60 ± 4 years; 44 (54%) were female. In late onset AD, age was 72 ± 5 years; 47 (52%) were female. Dementia severity and global cognitive decline did not differ between groups (early onset: MMSE: 20 ± 5, CAMCOG: 69 ± 15, late onset: MMSE: 21 ± 5, CAMCOG: 70 ± 15; p > 0.05). Early onset patients performed worse than late onset patients on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01). Late onset patients performed worse on memory, although not significantly (p = 0.11). Stratification for dementia severity showed that in mildly demented early onset patients, memory function was remarkably preserved compared to late onset patients (p < 0.01). In moderate AD, differences in memory function disappeared, but early onset patients performed worse on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01) than late onset patients. Adjustment for APOE left results unchanged. In conclusion, early onset AD presents with a different cognitive profile and the disease course seems different. Relative sparing of memory function in early stages stresses the need to adequately test other cognitive domains.     

Morphine exposure prevents up-regulation of MR and GR binding sites in the brain of adult male and female rats due to prenatal stress

Our previous work demonstrated that the hormone response to stress and the negative feedback inhibition to these hormones are sex-dependently altered by prenatal morphine exposure in adult rats. An alteration in the glucocorticoid negative feedback inhibition is mediated by glucocorticoid receptors (GR) that are distributed throughout the brain, and mineralocorticoid receptors (MR) localized mainly in the hippocampus and involved in a tonic influence of brain functions. Therefore, the present study examined the binding characteristics of MR and GR in young adult male and female rats exposed prenatally (E11-E18) to morphine (10 mg/kg/2 x /day), saline or no treatment at all (controls). At 60-90 days of age, animals were adrenalectomized (ADX) 24 h prior to decapitation. The hippocampus and hypothalamus were dissected for saturation binding assays. The data demonstrate that prenatal stress due to maternal saline injections up-regulates MR and GR binding in the hippocampus of adult male rats and this effect is prevented by prenatal morphine exposure. There is no effect of prenatal morphine exposure on GR binding in the hypothalamus of males. In female rats, prenatal morphine exposure does not affect the binding of MR and GR in the hippocampus or GR in the hypothalamus relative to controls; however, they are affected by ovarian hormone fluctuation. Moreover, prenatal stress decreases MR binding in the hippocampus of diestrous females and GR binding in the hypothalamus of estrous females. Both decreases are prevented by prenatal morphine exposure. Thus, the present study demonstrates that: (1) prenatal stress due to maternal saline injections alters MR and GR binding of adult male and female rats and is prevented by prenatal morphine exposure; (2) the MR and GR binding in adult female rats are affected by ovarian hormone fluctuations.     

Affective temperaments: psychometric properties of the Hungarian TEMPS-A

The study examines the psychometric properties of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) based on 717 (438 females and 279 males) healthy subjects in a Hungarian normative sample. The questionnaire is a self-report 110-item tool that postulates five affective temperaments: depressive, cyclothymic, irritable, hyperthymic, and anxious. Most of the TEMPS-A scales have excellent internal consistencies (0.78-0.84), except for the Depressive Temperament Scale, which had a Cronbach's alfa coefficient of 0.63. The item-analyses have identified a few deficient items which do not fit into the scale. In line with the literary data, women had higher mean scores on the depressive, cyclothymic, and anxious subscales, whereas men scored higher on the cyclothymic subscale. Cut-offs for each temperament were based on z-scores higher than + 2S.D. Dominant nervous-anxious (4.3%), depressive (3.8%), cyclothymic (3.2%), and irritable (3.2%) temperaments were the most common in this normative population, whereas dominant hyperthymic (1.8%) temperament was relatively uncommon. Factor analyses of the TEMPS-A items yielded considerable overlap between depressive and cognitive anxiety traits. The strongest correlation was observed between the anxious and the depressive temperament subscales in line with some international findings (r=0.62**). To test construct validity, we administered the Beck Depression Inventory, Profile of Mood States (shortened version) and the Cloninger Temperaments and Character Inventory, which all supported the validity of TEMPS-A subscales. Based on the results obtained with the Hungarian normative sample, the TEMPS-A is a reliable and valid instrument in personality psychology, and further refinement on clinical samples opens new and interesting research avenues.