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.

TRIGANO, A.J., ET AL.: Lead Explantation Late After Atrial Perforation. Tbis report describes the case of a patient in wbom atrial perforation witb penetration of tbe tboracic wall was diagnosed 2 years after tbe implantation of an Accufix lead. Despite tbis complication, atrial detection in the bipolar mode and ventricular pacing were normal. Digital fluoroscopy detected a fracture witb extrusion of a short segment of tbe retention wire. Tbe rupture of tbe retention wire might have been the result, but was not the cause of tbe perforation. (PACE 1996; 19:1268-1269 atrial perforation, Accufix^'^ atrial lead

is a common electrolyte disorder that frequently is overlooked and undertreated. Although the pathophysiological process of hyponatremia is complex, arginine vasopressin (AVP) is a common etiologic factor. Excess AVP release by osmotic or nonosmotic stimuli or both can lead to sodium and water imbalance. Conventional treatment options for hyponatremia, including water restriction and administration of sodium chloride with or without loop diuretics, do not directly address the underlying water retention induced by excess AVP in many cases. Clinical trials showed that AVP-receptor antagonists, including lixivaptan, tolvaptan, and conivaptan, produce aquaresis, the electrolyte-sparing excretion of free water, to correct serum sodium concentration. We review results from recent clinical trials involving AVP-receptor antagonists in the treatment of hyponatremia associated with AVP excess.

Background. During haemodialysis (HD), polymorphonuclear cells (PMNs) and platelets are activated and release various granule products, including myeloperoxidase (MPO) and platelet factor 4 (PF4). MPO triggers the generation of reactive oxygen species, leading to irreversible protein, carbohydrate and lipid modification. PF4 probably also contributes to oxidative stress. As previously shown, HD-induced PMN degranulation is almost completely abolished during citrate anticoagulation, most probably due to its calcium chelation ability. Methods. In the present study, apart from HDinduced PMN and platelet degranulation, oxidative stress was analysed during three modes of anticoagulation. Heparin, dalteparin and citrate (HD hep , HD dal and HD cit ) were compared in a randomized, crossover fashion in eight chronic HD patients. Multiple blood samples were taken during the third HD session of each modality, from both the afferent and efferent line. Besides the degranulation markers MPO and PF4, various markers of oxidative stress were measured, including oxidized low-density lipoprotein (ox-LDL), malondialdehyde (MDA) and carboxymethyllysine (CML). Results. During HD hep and HD dal , marked degranulation was observed shortly after the start of HD. In contrast, during HD cit , PF4 and MPO levels remained unaltered, suggesting no release at all. After 1 week of HD cit , ox-LDL levels were markedly reduced [median 26% (3-65%), P ¼ 0.01], if compared with HD hep and HD dal . As regards MDA and CML, no differences were found.

Aim: Review outcomes of ITI with recombinant factor VIII Fc fusion protein (rFVIIIFc) in patients with severe haemophilia A and high-titre inhibitors. Methods: Multicentre retrospective chart review of severe haemophilia A patients treated with rFVIIIFc for ITI. Results: Of 19 patients, 7 were first-time ITI and 12 were rescue ITI. Of 7 first-time patients, 6 had at least 1 high-risk feature for ITI failure. Four of 7 first-time patients were tolerized in a median of 7.8 months. The remaining 3 patients continue on rFVIIIFc ITI. Of 12 rescue patients, 7 initially achieved a negative Bethesda titre (≤0.6) in a median of 3.3 months, 1 had a decrease in Bethesda titre and continues on rFVIIIFc ITI and 4 have not demonstrated a decrease in Bethesda titre. Of these 4, 3 continue on rFVIIIFc ITI and 1 switched to bypass therapy alone. Two initially responsive patients transitioned to other factors due to recurrence. Overall, 16 of 19 patients remain on rFVIIIFc (prophylaxis or ITI). For those still undergoing ITI, longer follow-up is needed to determine final outcomes. No adverse events reported. Conclusions: Recombinant factor VIII Fc fusion protein demonstrated rapid time to tolerization in high-risk first-time ITI patients. For rescue ITI, rFVIIIFc showed therapeutic benefit in some patients who previously failed ITI with other products. These findings highlight the need to further evaluate the use of rFVIIIFc for ITI. K E Y W O R D S haemophilia A, immune tolerance induction, inhibitor, recombinant factor VIII Fc fusion protein, rescue therapy, retrospective chart review This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Mid-urethral synthetic slings (MUSS) have grown in acceptance and popularity to gain a foremost position in stress urinary incontinence (SUI) surgery. • There are numerous studies that provide a large amount of Level 1 and 2 evidence that support the concept of a sling placed at the level of the mid-urethra. • Long-term follow-up has been published for the original tension-free vaginal tape (TVT) procedure with the most recent publication providing Level 2 evidence with mean follow-up of 11.5 years of 69/91 (77%) of patients from the original series. There was objective cure was in 90% of women and 77% considered themselves subjectively cured, based on the Patient Global Impression of Improvement. • Level 1 evidence with long-term follow-up has been provided comparing colposuspension to TVT at 2 and 5 years. At 5 years for the primary efficacy variable of a negative 1 h stress pad test, there was no difference in success (81% vs 90%). • Two recent meta-analyses provide Level 1 evidence comparing outcomes for retropubic vs transobturator MUSS. One included 18 studies, randomized and cohort: cohort studies had a 12.3% failure rate for transobturator and 13.7% failure for the retropubic approach, randomized studies showed 5.7% failure in the transobturator vs 7.8% in the retropubic group. The other meta-analysis included 11 studies published 2008-2009, which found that the shortterm cure rate was borderline inferior for the transobturator tape group (odds ratio 0.62; 95% confidence interval 0.37-1.00), nearly reaching statistical significance (P = 0.05). • This review details further comparator evidence and evidence for use in specific patient groups (elderly, obese, intrinsic sphincter deficiency, mixed UI).

Multiple acyl-CoA dehydrogenase deficiency CoQ 10 deficiency Riboflavin Electron transfer flavoprotein ubiquinone oxidoreductase a b s t r a c t Multiple acyl-CoA dehydrogenase deficiency (MADD) is a metabolic disorder due to dysfunction of electron transfer flavoprotein (ETF) or ETF-ubiquinone oxidoreductase (ETF-QO). Mutations in ETFDH, encoding ETF-QO have been associated with both riboflavin-responsive and non-responsive MADD as well as a myopathic form of CoQ 10 deficiency, although pathomechanisms responsible for these different phenotypes are not well-defined. We performed mutation analysis in four Taiwanese MADD patients. Three novel ETFDH mutations were identified in four patients and all harbored the p.A84T mutation. Muscle CoQ 10 levels and respiratory chain activities measured in two patients were normal. Three patients improved on riboflavin together with carnitine. Our results show that not all MADD patients have CoQ 10 deficiency. Based upon our data, riboflavin and carnitine may be the first-line treatment for MADD.

Autosomal-dominant Alzheimer disease (ADAD) is a genetic disorder caused by mutations in Amyloid Precursor Protein (APP) or Presenilin (PSEN) genes. Studies from families with ADAD have been critical to support the amyloid cascade hypothesis of Alzheimer disease (AD), the basis for the current development of amyloid-based disease-modifying therapies in sporadic AD (SAD). However, whether the pathological changes in APP processing in the CNS in ADAD are similar to those observed in SAD remains unclear. In this study, we measured b-site APP-cleaving enzyme (BACE) protein levels and activity, APP and APP C-terminal fragments in brain samples from subjects with ADAD carrying APP or PSEN1 mutations (n = 18), patients with SAD (n = 27) and agematched controls (n = 22). We also measured sAPPb and BACE protein levels, as well as BACE activity, in CSF from individuals carrying PSEN1 mutations (10 mutation carriers and 7 non-carrier controls), patients with SAD (n = 32) and age-matched controls (n = 11). We found that in the brain, the pattern in ADAD was characterized by an increase in APP b-C-terminal fragment (b-CTF) levels despite no changes in BACE protein levels or activity. In contrast, the pattern in SAD in the brain was mainly characterized by an increase in BACE levels and activity, with less APP b-CTF accumulation than ADAD. In the CSF, no differences were found between groups in BACE activity or expression or sAPPb levels. Taken together, these data suggest that the physiopathological events underlying the chronic Ab production/clearance imbalance in SAD and ADAD are different. These differences should be considered in the design of intervention trials in AD.

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.

The renin-angiotensin-aldosterone system (RAAS) is important for the development of hypertension, and several antihypertensive drugs target this system. Our aim was to determine whether specific single nucleotide polymorphisms (SNPs) in RAAS genes were related to the blood pressure (BP) lowering effect of antihypertensive treatment. Methods: Patients with mild to moderate primary hypertension and left ventricular hypertrophy were randomized in a double-blind fashion to treatment with either the angiotensin II type 1 receptor antagonist irbesartan (n ϭ 48) or the ␤ 1 -adrenergic receptor blocker atenolol (n ϭ 49) as monotherapy. A microarray-based minisequencing system was used to genotype 30 SNPs in seven genes in the RAAS. These polymorphisms were related to the antihypertensive response after 12 weeks treatment. Results: The BP reductions were similar in the atenolol and the irbesartan groups. Presence of the angiotensinogen (AGT) -6A allele or the AGT 235T allele were both associated with the most pronounced systolic BP response to atenolol treatment (P ϭ .001 when -6 AAϩAG was compared with GG and P ϭ .008 for presence of the 235T variant compared with 235 MM).

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.

Comp lex regional pain syndrome (CRPS) can be a complication of injury or surgery or have an obscu re etiology. Special precautions are indicated (i.e., preemptive analgesia) when surgery is required with a patient who has been diagnosed with CRPS. The complex case of a 44-year-old female diagnosed with reflex sympathetic dystrophy (RSD) is discussed, including current treatment options. A brief review of the literature as well as the features of complex regional pain syndrome (CRPS IIRSD and CRPS I//causalgia) are presented.

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...

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Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environmentphenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders.

Purpose Religious delusions are common and are considered to be particularly difficult to treat. In this study we investigated what psychological processes may underlie the reported treatment resistance. In particular, we focused on the perceptual, cognitive, affective and behavioural mechanisms held to maintain delusions in cognitive models of psychosis, as these form the key treatment targets in cognitive behavioural therapy. We compared religious delusions to delusions with other content. Methods Comprehensive measures of symptoms and psychological processes were completed by 383 adult participants with delusions and a schizophrenia spectrum diagnosis, drawn from two large studies of cognitive behavioural therapy for psychosis. Results Binary logistic regression showed that religious delusions were associated with higher levels of grandiosity (OR 7.5; 95 % CI 3.9-14.1), passivity experiences, having internal evidence for their delusion (anomalous experiences or mood states), and being willing to consider alternatives to their delusion (95 % CI for ORs 1.1-8.6). Levels of negative symptoms were lower. No differences were found in delusional conviction, insight or attitudes towards treatment. Conclusions Levels of positive symptoms, particularly anomalous experiences and grandiosity, were high, and may contribute to symptom persistence. However, contrary to previous reports, we found no evidence that people with religious delusions would be less likely to engage in any form of help. Higher levels of flexibility may make them particularly amenable to cognitive behavioural approaches, but particular care should be taken to preserve self-esteem and valued aspects of beliefs and experiences.

Background Diabetes may cause cardiomyopathy characterized by cardiac fibrosis. Recent studies of genetically modified mice have elucidated a role of the natriuretic peptides (NP), type-A and type-B (ANP and BNP), and their common receptor [natriuretic peptide receptor (NPR), type-A] in development of cardiac fibrosis. The role of NP type-C (CNP) and NPR type-B ( NPR-B) in the heart is less well established. In this study we examined if diabetes alters heart expression of the genes encoding the NP and its receptors.

We performed two studies. Study 1 was a construct validation of Seniors in the Community: Risk Evaluation for Eating and Nutrition (SCREEN), a 15-item questionnaire for assessing nutritional risk. In Study 2, we examined the test-retest reliability of SCREEN.

Background: During bladder filling, the trigone contracts help keep the ureteral orifices open and the bladder neck shut. The trigone generates spontaneous activity as well as responding to neuromuscular transmitters, but the relationship between these phenomena are unclear. Objectives: To characterise the cellular mechanisms that regulate and modify spontaneous activity in trigone smooth muscle. Design, setting, and participants: Muscle strips from the superficial trigone of male guinea-pigs were used for tension experiments and immunofluorescent studies. Measurements: In isolated trigonal cells, intracellular Ca 2+ was measured by epifluorescence microscopy using the fluorescent Ca 2+ indicator Fura-2. Results and limitations: Spontaneous intracellular Ca 2+ transients and contractions were observed in trigonal single cells and strips and were significantly higher compared to the bladder dome. Ca-free superfusate and verapamil terminated spontaneity. T-type Ca 2+ channel block with NiCl 2 depressed slightly Ca 2+ transients but not spontaneous contractions. Neither the BK Ca channel blocker iberiotoxin nor the SK Ca channel blocker apamin had any effect on single cell activity. By contrast, the Cl À channel blocker niflumic acid attenuated significantly both Ca 2+ transients and muscle contractions. Agonist stimulation (carbachol, phenylephrine) up-regulated activity. Gap junction labelling (Cx43) was approximately 5 times denser in the trigone than in detrusor smooth muscle. The gap junction blocker 18-ß-glycyrrhetinic acid modulated spontaneous contractions in the trigone but not in the bladder dome. Conclusions: Trigone myocytes employ membrane L-type-Ca 2+ channels and Cl À channels to generate spontaneous activity. Intercellular electrical coupling ensures its propagation and, thus, sustains contraction of the whole trigone.

Hydrogen gas, which is produced during fermentation in the human colon, is either excreted in breath or metabolised by gut bacteria through a variety of pathways. These may include methanogenesis, dissimilatory sulphate reduction, and acetogenesis. To determine which of these routes predominates in the large intestine, stools were taken from 30 healthy subjects and incubated as 5% (w/v) slurries with Lintner's starch. In 23 of 30 subjects, methane production was the main method of hydrogen disposal. In the remaining seven, high rates of sulphate reduction were recorded together with raised production of H2S. All samples showed relatively low rates of hydrogen evolution and of acetate formation from CO2 and H2. Sulphate reduction and

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 evaluate the ability of two cryopreservation methods and three cryoprotectants to preserve sperm quality. Design: A prospective clinical study. Setting: Male infertility clinic at a tertiary healthcare center. Patient(s): Twenty infertile men and 10 healthy donors. Intervention(s): In the first experiment, semen was cryopreserved by either the Irvine Scientific method (IS) or the Cleveland Clinic Foundation (CCF) method. In the second experiment, semen was cryopreserved by the IS method and one of three cryoprotectants: TES and Tris yolk buffer, Sperm Freezing Medium, or Enhance Sperm Freeze. Main Outcome Measure(s): Postthaw sperm motility, cryosurvival, and kinematics. Result(s): Percentages of postthaw sperm motility and cryosurvival were higher in the IS cryopreservation method compared with in the CCF method (15.94 Ϯ 9.19 vs. 12.07 Ϯ 7. 31 and 47.42 Ϯ 17.44 vs. 35.76 Ϯ 17.56). However, the CCF method resulted in significantly better sperm kinematics. Postthaw motility in the donors and patients was highest in the samples frozen in TES and Tris yolk buffer medium.

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 ...

BACKGROUND CONTEXT: Low back pain (LBP) is associated with high health-care utilization and lost productivity. Numerous interventions are routinely used, although few are supported by strong evidence. Cost utility analyses (CUAs) may be helpful to inform decision makers. PURPOSE: To conduct a systematic review of CUAs of interventions for LBP. STUDY DESIGN: Systematic review. METHODS: A search strategy combining medical subject headings and free text related to LBP and health economic evaluations was executed in MEDLINE. Cost utility analyses combined with randomized controlled trials for LBP were included. Studies that were published before 1998, non-English, decision analyses, and duplicate reports were excluded. Search results were evaluated by two reviewers, who extracted data independently related to clinical study design, economic study design, direct cost components, utility results, cost results, and CUA results. RESULTS: The search produced 319 citations, and of these 15 met eligibility criteria. Most were from the United Kingdom (n58), published in the past 3 years (n512), studied chronic LBP or radiculopathy (n513), and had a follow-up O12 months (n513). Combined, there were 33 study groups who received a mean 2.1 interventions, most commonly education (n517), exercise therapy (n513), spinal manipulation therapy (n57), surgery (n57), and usual care from a general practitioner (n57). Mean baseline utility was 0.57, improving to 0.67 at follow-up; the mean difference in utility improvement between study groups was 0.04.

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.

Persons at high risk for human immunodeficiency virus (HIV) infection are also likely to be at risk for other infectious pathogens, including hepatitis B virus (HBV) or hepatitis C virus (HCV). These are bloodborne pathogens transmitted through similar routes; for example, via injection drug use (IDU), sexual contact, or from mother to child during pregnancy or birth. In some settings, the prevalence of coinfection with HBV and/or HCV is high. In the context of effective antiretroviral therapy (ART), liver disease has emerged as a major cause of morbidity and mortality in HIV-infected persons. Further, coinfection with viral hepatitis may complicate the delivery of ART by increasing the risk of drug-related hepatoxicity and impacting the selection of specific agents (e.g., those dually active against HIV and HBV). Expert guidelines developed in the United States and Europe recommend screening of all HIV-infected persons for infection with HCV and HBV and appropriate management of those found to be chronically infected. Treatment strategies for HBV infection include the use of nucleos(t)ide analogues with or without anti-HIV activity and/or peginterferon alfa (PegIFN) whereas HCV treatment is limited to the combination of PegIFN and ribavirin (RBV). Current approaches to management of HIVinfected persons coinfected with HBV or HCV are discussed in this review.

The regenerative decline of organisms during ageing is linked to the reduced proliferative activity, impaired function and exhaustion of tissue-specific stem and progenitor cells. Studies using heterochronic parabiosis, involving the surgical attachment of young and old organisms so that they share a common vascular system, have revealed that the systemic environment has a profound effect on stem cell function. In particular, specific youthful rejuvenating circulatory factors reverse age-related declines in stem cell function, whereas the old milieu contains inhibitory factors that impede stem cell function in young animals. Similarly, the effects of certain dietary interventions, namely calorie restriction, also induce a more youthful cellular and molecular phenotype in ageing stem cells throughout the body. Further to this, there are key molecular pathways involved in translating the availability of nutrients into altered stem cell function, including signalling in the insulin and insulin-like growth factor and mechanistic target of rapamycin (mTOR) pathways. In this review, we discuss the potential role of dietary interventions to promote a more rejuvenating systemic milieu in order to enhance stem cell function and promote healthy ageing.

Prematurely born children are at increased risk for cognitive deficits, but the neurobiological basis of these findings remains poorly understood. Since variations in neural circuitry may influence performance on cognitive tasks, recent investigations have explored the impact of preterm birth on connectivity in the developing brain. Diffusion tensor imaging studies demonstrate widespread alterations in fractional anisotropy, a measure of axonal integrity and microstructural connectivity, throughout the developing preterm brain. Functional connectivity studies report that preterm neonates, children and adolescents exhibit alterations in both resting state and task-based connectivity when compared to term control subjects. Taken together, these data suggest that neurodevelopmental impairment following preterm birth may represent a disease of neural connectivity.

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...

Background: Pancreatic pseudocyst endoscopic drainage has been described as a good treatment option, with morbidity and mortality rates that are lower than surgery. The aim of our study is to describe the efficacy of different forms of endoscopic drainage and estimate pseudocyst recurrence rate after short follow up period.