Clinical Sciences

B-chronic lymphocytic leukaemia (B-CLL) is a heterogeneous disease characterized by an accumulation of B lymphocytes expressing CD5. To date, the biological significance of this molecule in B-CLL B cells remains to be elucidated. In this study, we have analysed the functional consequences of the binding of an anti-CD5 antibody on B-CLL B cells. To this purpose, we have measured the percentage of viability of B-CLL B cells in the presence or in the absence of anti-CD5 antibodies and also examined some of the biochemical events downstream the CD5-signalling. We demonstrate that anti-CD5 induces phosphorylation of protein tyrosine kinases and protein kinase C (PKC), while no activation of Akt/PKB and MAPKs is detected. This signalling cascade results in viability in a group of patients in which we observe an increase of Mcl-1 levels, whereas the levels of bcl-2, bcl-xL and XIAP do not change. We also report that this pathway leads to IL-10 production, an immunoregulatory cytokine that might act as an autocrine growth factor for leukaemic B cells. Inhibition of PKC prevents the induction of Mcl-1 and IL-10, suggesting that the activation of PKC plays an important role in the CD5-mediated survival signals in B cells from a subset of B-CLL patients.

This study investigated the relationship between the perception of family functioning and depressive symptomatology in individuals with eating disorders (EDs). Subjects were evaluated by diagnostic clinical interview using DSM-III-R criteria for EDs, the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L), and two self-report measures, the Beck Depression Inventory (BDI) and the Family Assessment Device (FAD). A significant association was found between self-reported depressive symptomatology and perceived poor family functioning. Subjects with bulimia nervosa (BN) reported a significantly more dysfunctional family background than subjects with anorexia nervosa (AN). In our sample, the presence of self-reported depressive symptomatology was a more powerful predictive variable for perceived family dysfunction than the diagnosis of affective disorder. Also, the diagnosis of BN was a more consistent predictor of dysfunctional family interaction than the diagnosis of affective disorder. Depressive symptoms and EDs seem to play different roles in the way in which they contribute to dysfunctional family patterns.

Mitochondrial DNA depletion syndromes (MDSs) form a group of autosomal recessive disorders characterized by profoundly decreased mitochondrial DNA copy numbers in affected tissues. Three main clinical presentations are known: myopathic, encephalomyopathic and hepatocerebral. The first is associated with mutations in thymidine kinase 2 (TK2) and p53-induced ribonucleotide reductase B subunit (RRM2B); the second with mutations in succinate synthase A (SUCLA2) and B (SUCLG1); the third with mutations in Twinkle (PEO1), pol-γA (POLG1), deoxyguanosine kinase (DGUOK) and MPV17 (MPV17). In this work, we review the MDS-associated phenotypes and present our own experience of 32 MDS patients, with the aim of defining the mutation frequency of the known genes, the clinical spectrum of the diseases, and the genotype–phenotype correlations. Five of our patients carried previously unreported mutations in one of the eight MDS genes.

Diet induced changes in gut microbial composition and dysregulated immune responses are key players in the progression of metabolic syndrome (MetSyn) and obesity.The lymphatics that are directly exposed to the gut microbiota in the mesenteric bed are central players in inflammatory and immune responses and are impaired during MetSyn. However, the mechanisms remain unknown.Endogenous tryptophan derived gut microbiota metabolites such as indole, significantly limits inflammation and immune response. We hypothesize that microbiota influence the lymphatic mesenteric microenvironment via such discrete metabolites to impact metabolic disease. We evaluated the effects of indole, tryptamine and indole-3-acetate (I-3A) on inflammatory mechanisms in vitro and in vivo using cultured models of lymphatic endothelium (HDLECs) and rat models of high fructose diet induced MetSyn and LPS induced acute inflammation. HDLECs were treated with varying doses of indole, tryptamine and I-3A (100uM-500uM) i...

Purpose A eutectic mixture of local anesthetics (EMLA) is commonly used to provide topical anesthesia for intravenous (iv) cannulation. One of its side effects is vasoconstriction, which may render cannulation more difficult. A gel formulation of amethocaine (Ametop™) is now commercially available. The aim of this study was to compare EMLA and Ametop™ with regard to the degree of topical anesthesia afforded, the incidence of vasoconstriction and the ease of iv cannulation. Methods Thirty two ASA 1 adult volunteers had a # 16 gauge iv cannula inserted on two separate occasions using EMLA and Ametop™ applied in a double blind fashion for topical anesthesia. Parameters that were recorded after each cannulation included visual analogue pain scores (VAPS), the presence of vasoconstriction and the ease of cannulation, graded as: 1 = easy, 2 = moderately difficult, 3 = difficult and 4 = failed. Results The mean VAPS ± SD after cannulation with Ametop™ M was 12 ± 9.9 and with EMLA was 25.3 ± 16.6 (P = 0.002). Vasoconstriction occurred after EMLA application on 17 occasions and twice after Ametop™ (P = 0.001). The grade of difficulty of cannulation was 1.44 ± 0.88 following EMLA and 1.06 ± 0.25 with Ametop™ (P = 0.023). Conclusions Intravenous cannulation was less painful following application of Ametop™ than EMLA. In addition, Ametop™ caused less vasoconstriction and facilitated easier cannulation. Its use as a topical anesthetic agent is recommended, especially when iv access may be problematic. Objectif Un mélange eutectique d’anesthésiques locaux (MEAL) est souvent utilisé pour l’anesthésie topique lors d’une canulation intraveineuse (iv). La vasoconstriction, qui est l’un des effets secondaires du MEAL, peut compliquer la mise en place d’une canule. Une présentation en gel d’améthocaïne (Ametop™) est maintenant offerte dans le commerce. Le but de la présente étude était de comparer le MEAL et l’Ametop™ en regard du degré d’anesthésie topique fourni, de l’incidence de la vasoconstriction et de la facilité de la canulation iv. Méthode: On a inséré, en deux occasions séparées chez 32 volontaires adultes d’état physique ASA 1, une canuleiv de calibre 16 en utilisant en double aveugle le MEAL et Ametop™ pour réaliser l’anesthésie topique. Après chaque canulation, on a enregistré les paramètres suivants: les scores de douleur à l’échelle visuelle analogue (EVA), la présence de vasoconstriction et la facilité de canulation notée 1 = facile, 2 = modérément difficile, 3 = difficile et 4 = impossible. Résultats Les scores moyens à l’EVA ± l’écart type ont été de 12 ± 9,9 à la suite de la canulation avec Ametop™ M et de 25,3 ± 16,6 après le MEAL (P = 0,002). La vasoconstriction est survenue en 17 occasions après l’application du MEAL et deux fois plus souvent après Ametop™ (P = 0,001). Le degré de difficulté de canulation a été de 1,44 ± 0,88 après le MEAL et de 1,06 ± 0,25 après Ametop™ (P = 0,023). Conclusion La canulation intraveineuse est moins douloureuse après l’application d’Ametop™ que celle du MEAL. De plus, l’Ametop™ a provoqué moins de vasoconstriction et a facilité l’introduction d’une canule. Son usage comme anesthésique topique est recommandé, surtout lorsqu’une action rapide est nécessaire ou que l’accèsiv peut être problématique.

More than 20 years ago Habib Davanloo coined the term unlocking of the unconscious to describe how the psychodynamic concept of the human unconscious can become accessible using the technique of Intensive Short-Term Dynamic Psychotherapy (ISTDP). According to Davanloo, the possibility that unconscious material will be revealed is greatly increased when therapeutic efforts promote dominance of the unconscious therapeutic alliance over unconscious resistance. When these ingredients are present there is a psychic shift that allows unacceptable painful feelings to come to the surface. Toward adding further empirical support for the concept, in this article we compare outcomes between patients who experienced one or more major unlocking of the unconscious (N = 57) to those who did not experience major unlocking (N = 32) during ISTDP treatment. Significant and widespread differences were seen between these two groups, those with major unlocking had greater symptom reduction, interpersonal...

Dermatologists are increasingly confronted with patients affected by body dysmorphic disorder (BDD). BDD is characterized by excessive preoccupation with one or more perceived defect(s) or flaw(s) in physical appearance which are not observable or appear slight to others. So far, there have been only few studies examining the prevalence of BDD in dermatological outpatients. In addition, the need for psychotherapeutic support in dermatological outpatients with body dysmorphic concerns has not yet been systematically examined. The objective of the present study was therefore to investigate the frequency of body dysmorphic concerns as well as social adaptation and the need for psychotherapeutic support in the aforementioned patient group. A total of 252 dermatological outpatients seen at a German university hospital were consecutively enrolled, and examined using the Dysmorphic Concerns Questionnaire, the Social Adaptation Self-Evaluation Scale, and the German version of the University...

Objective To define the origin of radiculopathy of patients with degenerative lumbar scoliosis and to assess the correlation between percentage of radiculating pain relief with selective nerve root injections and lateral canal dimensions. Methods Ninety-three consecutive ...

Although functional and clinical outcomes after total ankle arthroplasty have been promising, a steep learning curve has been recognized. In addition, the performance of concomitant hindfoot realignment procedures is controversial. The purpose of this study was to report on a single surgeon's experience with the first 50 total ankle arthroplasty procedures. We wanted to define the characteristics of the learning curve and whether the rate of complications was increased in patients who required complex reconstruction for preexistent foot and ankle deformities. This was a retrospective study of 50 cases with an average follow-up of 24.2 months. The patient population consisted of 18 men and 30 women with an average age of 57.6 years. Twenty-six percent of the cases had concomitant bony realignment procedures, while 20% had prior history of major hindfoot corrective procedures. There were 19 cases with intraoperative malleolar fractures, 12 cases that exhibited some degree of malalignment, and 6 cases of syndesmotic nonunion, and 8 ankles required early component revision. Minor wound complications that resolved with local wound care occurred in 9 cases, while 1 patient had a major wound complication requiring flap coverage. Each of these complications, other than wound complications, decreased with the surgeon's experience. Our results also indicate that the performance of major realignment procedures at the same time of implant arthroplasty is not associated with an increased incidence of complications. The results of this study suggest that total ankle arthroplasty is associated with a learning curve. Perioperative complications may potentially decrease with surgeon experience.

A remote magnetic navigation system (MNS) is available and has been used with a 4-mm-tip magnetic catheter for radiofrequency (RF) ablation of some supraventricular and ventricular arrhythmias; however, it has not been evaluated for the ablation of cavotricuspid isthmus-dependent right atrial flutter (AFL). The present study evaluates the feasibility and efficiency of this system and the newly available 8-mm-tip magnetic catheter to perform RF ablation in patients with AFL. Twenty-six consecutive patients (23 men, mean age 64.6 +/- 9.6 years) underwent RF ablation using a remote MNS. RF ablation was performed with an 8-mm-tip magnetic catheter (70 degrees C, maximum power 70 W, 90 seconds). The endpoint of ablation was complete bidirectional isthmus block. To assess a possible learning curve, procedural data were compared between the first 14 (group 1) and the rest (group 2) of the patients. The initial rhythm during ablation was AFL in 20 (19 counterclockwise and 1 clockwise) and s...