Showing papers by "Hospital Universitario La Paz published in 2006"

EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population.

Abstract: Aims The objective of the EuroHeart Failure Survey II (EHFS II) was to assess patient characteristics, aetiology, treatment, and outcome of acute heart failure (AHF) in Europe in relation to the guidelines on the diagnosis and treatment of AHF published by the European Society of Cardiology. Methods and results Patients hospitalized for AHF were recruited by 133 centres in 30 European countries. Three thousand five hundred and eighty patients were entered into the database by the end of August 2005. Mean age was 70 years, and 61% of patients were male. New-onset AHF ( de novo AHF) was diagnosed in 37%, of which 42% was due to acute coronary syndromes (ACS). Clinical classification according to the guidelines divided AHF patients into (i) decompensated HF (65%), (ii) pulmonary oedema (16%), (iii) HF and hypertension (11%), (iv) cardiogenic shock (4%), and (v) right HF (3%). Coronary heart disease, hypertension, and atrial fibrillation were the most common underlying conditions. Arrhythmias, valvular dysfunction, and ACS were each present as precipitating factor in one-third of cases. Preserved left ventricular ejection fraction (≥45%) was observed in 34%. Valvular disorders were common, especially mitral regurgitation (MR) which was reported on echocardiography in 80% of patients. Median length of stay was 9 days, and in-hospital mortality 6.7%. At discharge, 80% of patients were on angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers, whereas 61% were taking beta-blocker medication. Conclusion Decompensated HF is the most common clinical presentation of AHF patients. More than one-third of AHF patients do not have a previous history of HF, and new-onset HF is often caused by ACS. Preserved systolic function is found in a substantial proportion of the patients. The prevalence of valvular dysfunction is strikingly high and contributes to the clinical presentation. The EHFS II on AHF verified that the use of evidence-based HF medication was well adopted to clinical practice.

HRAS mutation analysis in Costello syndrome: Genotype and phenotype correlation

Abstract: Costello syndrome is a rare condition comprising mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy, and/or atrial tachycardia), tumor predisposition, and skin and musculoskeletal abnormalities. Recently mutations in HRAS were identified in 12 Japanese and Italian patients with clinical information available on 7 of the Japanese patients. To expand the molecular delineation of Costello syndrome, we performed mutation analysis in 34 North American and 6 European (total 40) patients with Costello syndrome, and detected missense mutations in HRAS in 33 (82.5%) patients. All mutations affected either codon 12 or 13 of the protein product, with G12S occurring in 30 (90.9%) patients of the mutation-positive cases. In two patients, we found a mutation resulting in an alanine substitution in position 12 (G12A), and in one patient, we detected a novel mutation (G13C). Five different HRAS mutations have now been reported in Costello syndrome, however genotype-phenotype correlation remains incomplete.

De novo gene conversion in the RCA gene cluster (1q32) causes mutations in complement factor H associated with atypical hemolytic uremic syndrome

Abstract: Many of the complement regulatory genes within the RCA cluster (1q32) have arisen through genomic duplication and the resulting high degree of sequence identity is likely to predispose to gene conversion events. The highest degree of identity is between the genes for factor H (CFH) and five factor H-related proteins--CFHL1, CFHL2, CFHL3, CFHL4, and CFHL5. CFH mutations are associated with atypical hemolytic uremic syndrome (aHUS). In the Newcastle cohort of 157 aHUS patients we have identified CFH mutations in 25 families or individuals. Eleven of these 25 independent mutations are either c.3226C>G,Q1076E; c.3572C>T,S1191L; c.3590T>C,V1197A or combined c.3572C>T,S1191L/c.3590T>C,V1197A. Sequence analysis shows that all four of these changes could have arisen as a result of gene conversion between CFH and CFHL1. Analysis of parental samples in two patients with S1191L/V1197A has shown that the changes are de novo thus providing conclusive evidence that gene conversion is the mutational mechanism in these two cases. To confirm that S1191L and V1197A are disease predisposing we examined their functional significance in three ways - analysis of the C3b/C3d binding characteristics of recombinant mutant S1191L/V1197A protein, heparin affinity chromatography and haemolytic assays of serum samples from aHUS patients carrying these changes. The results showed that these changes resulted in impaired C3b binding and a defective capacity to control complement activation on cellular surfaces. We, therefore, provide conclusive evidence that gene conversion is responsible for functionally significant CFH mutations in aHUS.

Images in cardiovascular medicine. Pheochromocytoma-related cardiomyopathy: inverted Takotsubo contractile pattern.

Abstract: A 41-year-old woman with no history of cardiac disease or hypertension was admitted to the intensive care unit with acute headache, psychomotor agitation, diaphoresis, nausea, and vomiting. A cerebral computed tomography scan ruled out subarachnoid hemorrhage. The ECG showed sinus tachycardia with ST-segment depression in leads V3–V6, II, III, and aVF. The troponin I level was elevated. The patient continued to have progressive respiratory deterioration, which required mechanical ventilation 24 hours after admission. She also developed 6 episodes of electromechanical dissociation, with circulatory recovery after successful cardiopulmonary resuscitation. Transthoracic echocardiography revealed severe left ventricular dysfunction and a contractile abnormality, …

Epithelial-to-mesenchymal transition of the mesothelial cell--its role in the response of the peritoneum to dialysis.

Abstract: Peritoneal membrane fibrosis, ranging from mild inflammation to severe sclerosing peritonitis, is one of the complications of peritoneal dialysis (PD). In parallel with fibrosis, the peritoneum shows a progressive increase of capillaries and vasculopathy, involved in increased small solute transport across the membrane and ultrafiltration failure. Glucose and glucose degradation products from PD solutions are responsible of stimulating transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) production by mesothelial cells (MCs). TGF-beta is a potent pro-fibrotic factor and inducer of epithelial-to-mesenchymal transition (EMT) of the MC. Local production of VEGF by transitional MC appears to play a central role in the processes leading to peritoneal angiogenesis. This review addresses the mechanism involved in peritoneal structural alteration by dialysis and points to the EMT of MC as the initiating mechanism of peritoneal injury. Information from multiple origins about TGF-beta and VEGF is integrated into EMT process in a comprehensive manner. Regulation and new targets for inhibition of EMT or its deleterious effects are discussed.

Dopamine Versus Epinephrine for Cardiovascular Support in Low Birth Weight Infants: Analysis of Systemic Effects and Neonatal Clinical Outcomes

Abstract: BACKGROUND.Early postnatal adaptation to transitional circulation in low birth weight infants frequently is associated with low blood pressure and decreased blood flow to organs. Catecholamines have been used widely as treatment, despite remarkably little empirical evidence on the effects of vasopressor/inotropic support on circulation and on clinically important outcomes in sick newborn infants. AIMS.To explore the effectiveness of low/moderate-dose dopamine and epinephrine in the treatment of early systemic hypotension in low birth weight infants, evaluate the frequency of adverse drug effects, and examine neonatal clinical outcomes of patients in relation to treatment. DESIGN/METHODS.Newborns of 1501-g birth weight or 32 weeks of gestational age, with a mean blood pressure lower than gestational age in the first 24 hours of life, were assigned randomly to receive dopamine (2.5, 5, 7.5, and 10 g/kg per minute; n 28) or epinephrine (0.125, 0.250, 0.375, and 0.5 g/kg per minute; n 32) at doses that were increased stepwise every 20 minutes until optimal mean blood pressure was attained and maintained (responders). If this treatment was unsuccessful (nonresponders), sequential rescue therapy was started, consisting first of the addition of the second study drug and then hydrocortisone. OUTCOME MEASURES.These included: (1) short-term changes (first 96 hours, only responders) in heart rate, mean blood pressure, acid-base status, lactate, glycemia, urine output, and fluid-carbohydrate debit; and (2) medium-term morbidity, enteral nutrition tolerance, gastrointestinal complications, severity of lung disease, patent ductus arteriosus, cerebral ultrasound diagnoses, retinopathy of prematurity, and mortality. RESULTS.Patients enrolled in this trial did not differ in birth weight or gestational age (1008 286 g and 28.3 2.3 weeks in the dopamine group; 944 281 g and 27.7 2.4 weeks in the epinephrine group). Other main antenatal variables were also comparable. However, responders and nonresponders differed significantly with

Peripheral blood T lymphocytes from patients with early rheumatoid arthritis express RANKL and interleukin-15 on the cell surface and promote osteoclastogenesis in autologous monocytes.

Abstract: Objective To investigate the osteoclastogenic potential of T cells from the peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) on autologous monocytes, and to study the cytokines implicated in this process. Methods T cells and monocytes were isolated from the PB of 20 healthy subjects and 20 patients with early RA, and from the SF of 20 patients with established RA. Autologous T cell/monocyte cocultures were established in the absence of exogenous cytokines or growth factors in order to examine spontaneous ex vivo osteoclast differentiation by tartrate-resistant acid phosphatase staining and calcified matrix resorption activity. Results Surface RANKL was expressed on freshly isolated T cells from the PB of patients with early RA and the SF of patients with established RA. In addition, surface interleukin-15 (IL-15) was detected on freshly isolated T cells and monocytes from the PB of patients with early RA and the SF of patients with established RA. Autologous T cell/monocyte cocultures derived from the SF of patients with established RA and from the PB of patients with early RA, but not from the PB of healthy controls, resulted in osteoclast differentiation that was significantly inhibited by osteoprotegerin (OPG) and by neutralizing monoclonal antibodies to IL-15, IL-17, tumor necrosis factor α (TNFα), and IL-1β. OPG, anti-TNFα, and anti–IL-1β demonstrated a cooperative inhibitory effect. At 1-year followup, surface RANKL and IL-15 and ex vivo osteoclastogenesis were no longer observed on PB T cells or monocytes from patients with early RA in whom clinical remission had been achieved with treatment. Conclusion T cells are important contributors to the pathogenesis of bone erosions in RA through interaction with osteoclast precursors of the monocyte/macrophage lineage.

Epidemiology of osteoporotic hip fractures in Spain

Abstract: We conducted a multicentre study, divided into a retrospective and a prospective portion. The retrospective study evaluated osteoporotic hip fractures that occurred during 2002. The prospective study evaluated osteoporotic hip fractures that occurred during May 2003. The study was conducted in 77 hospitals in Spain and comprised patients 60 years of age and over. In the retrospective study we registered 13,195 hip fractures. Of the patients, 74% were women and 26% were men. The mean age was 80.7±8.4 years. The average incidence was 6.94±0.44 hip fractures per 1,000 inhabitants/year (95% CI, 6.07–7.82). In the prospective study, we registered 1,399 hip fractures. This represents a monthly incidence of 0.60±0.04 hip fractures per 1,000 inhabitants/year (95% CI, 0.51–0.69). Of the subjects, 74% were women and 26% were men. The mean age was 81.4±8.1 years. Using these data, we calculated the average annual prevalence in 2003 to be 7.20 fractures per 1,000 inhabitants. Thirty-three percent had previously suffered a hip fracture. Prior to the fracture, only 18% had received medical treatment for osteoporosis. After discharge from the hospital, only 26% were receiving pharmacological treatment for osteoporosis.

Obstructive sleep apnoea-hypoapnoea syndrome reversibly depresses cardiac response to exercise.

Abstract: Aims To evaluate cardiac response to exercise in middle-aged normotensive obstructive sleep apnoea–hypoapnoea syndrome (OSAHS) adults with normal resting left ventricular systolic function and to test the hypothesis that nasal continuous positive airway pressure (CPAP) therapy might improve cardiac performance during exercise. Methods and results We performed a prospective, randomized, double-blind, placebo-controlled, cross-over clinical trial including 31 consecutive newly diagnosed OSAHS patients and 15 healthy subjects. Cardiopulmonary exercise testing with cardiac output measurement, blood pressure (BP) recordings, and urinary excretion of catecholamine levels were obtained at baseline and after 3 months on both effective and sham CPAP. OSAHS subjects had higher systolic and mean nocturnal BP and higher nocturnal levels of catecholamines. In contrast, they had lower increments in cardiac output (Qt) and in stroke volume (SV) in response to exercise than control subjects. CPAP therapy was associated with highly significant improvements in all the indices of left ventricular systolic performance response during exercise, whereas with sham CPAP, all of them remained unchanged. Conclusion OSAHS patients with normal resting left ventricular systolic function and no hypertension had a worse cardiac response to exercise than healthy subjects. In these patients, 3 months of CPAP improved both Qt and SV responses to exercise.

Long-term effects of highly active antiretroviral therapy in pretreated, vertically HIV type 1-infected children: 6 years of follow-up.

Abstract: Background. Several studies of children with human immunodeficiency virus (HIV) type 1 infection have demonstrated sustained increases in CD4 + cell count, even when virological failure has occurred after receipt of highly active antiretroviral therapy (HAART), but these studies were of limited duration. Moreover, the CD4 + cell count threshold at which antiretroviral treatment should be initiated is still unsettled. The aim of this study was to define the long-term impact of HAART on CD4 + cell percentage and viral load according to CD4 + cell percentages before HAART was initiated. Methods. We conducted a retrospective study of 113 pretreated HIV-1-infected children stratified by preHAART CD4 + cell percentage ( 25%). The inclusion criteria were as follows: initiating HAART with a protease inhibitor, having 6 years of follow-up after starting HAART, having a CD4 + cell count or viral load recorded before initiation of HAART, and having received mono- or dual-nucleoside therapy before starting HAART. Results. During the first 2 years of HAART, HIV-1-infected children experienced a significant increase in CD4 + cell percentage and a decrease in viral load (P 25% after 6 years of HAART. Children with CD4 + cell percentages of 5%-25% at baseline had a strong negative association with achieving CD4 + cell percentages of >30% for at least 6 and 12 months but not with achieving CD4 + cell percentages of >30% for at least 24 months. Conclusions. Long-term HAART allowed for restoration of CD4 + cell counts and control of viral loads in HIV-1-infected children. However, initiating HAART after severe immunosuppression has occurred is detrimental for the restoration of the CD4 + cell count.

Ex vivo analysis of dialysis effluent-derived mesothelial cells as an approach to unveiling the mechanism of peritoneal membrane failure.

Abstract: During peritoneal dialysis (PD), the peritoneum is exposed to bioincompatible dialysis fluids, which causes progressive fibrosis and angiogenesis and, ultimately, ultrafiltration failure. In addition, repeated episodes of peritonitis or hemoperitoneum may accelerate all these processes. Fibrosis has been classically considered the main cause of peritoneal membrane functional decline. However, in parallel with fibrosis, the peritoneum also displays increases in capillary number (angiogenesis) and vasculopathy in response to PD. Nowadays, there is emerging evidence pointing to peritoneal microvasculature as the main factor responsible for increased solute transport and ultrafiltration failure. However, the pathophysiologic mechanism(s) involved in starting and maintaining peritoneal fibrosis and angiogenesis remain(s) elusive. Peritoneal stromal fibroblasts have been considered (for many years) the cell type mainly involved in structural and functional alterations of the peritoneum; whereas mesothelial cells have been considered mere victims of peritoneal injury caused by PD. Recently, ex vivo cultures of effluent-derived mesothelial cells, in conjunction with immunohistochemical analysis of peritoneal biopsies from PD patients, have identified mesothelial cells as culprits, at least in part, in peritoneal membrane deterioration. This review discusses recent findings that suggest new peritoneal myofibroblastic cells may arise from local conversion of mesothelial cells by epithelial-to-mesenchymal transition during the repair responses that take place in PD. The transdifferentiated mesothelial cells may retain a permanent mesenchymal state, as long as initiating stimuli persist, and contribute to PD-induced fibrosis and angiogenesis, and hence to membrane failure. Future therapeutic interventions could be designated in order to prevent or reverse epithelial-to-mesenchymal transition of mesothelial cells, or its pernicious effects.

Clinical outcomes improve with highly active antiretroviral therapy in vertically HIV type-1-infected children.

Abstract: Background Use of antiretroviral therapy has resulted in a decrease in morbidity and mortality rates in human immunodeficiency virus type 1 (HIV-1)-infected childrenMethods We performed a retrospective study involving 427 children to determine the effectiveness of different antiretroviral therapy protocols on clinical outcome The follow-up period was divided into 5 calendar periods (CPs): CP1 (1980-1989), before antiretroviral therapy was administered; CP2 (1990-1993), when monotherapy was administered; CP3 (1994-1996), when combined therapy was administered; CP4 (1997-1998), when /=60% of children were receiving HAARTResults Children experienced a progressive increase in the CD4(+) cell count and decrease in the viral load from 1997 onwards A lower number of AIDS cases and deaths occurred during CP5 than during the other CPs (P 20 and a relative risk of survival of >30 The AIDS rate was >50% in CP1; we observed a very strong decrease to 14% in CP2, to 16% in CP3, to 7% in CP4, and to 2% in CP5 The mortality rates in CP2 and CP3 were >6% and thereafter decreased to 05% in CP5 The relative risks for no hospital admission in CP4 and CP5 were >35 The total rates of hospital admission in CP1, CP2, and CP3 were >30%; we observed a decrease in CP4 and CP5 The duration of hospitalization decreased during the follow-up period, and it was higher in CP1 (~30 days) than in the other periodsConclusions We observed that HAART produces a decrease in adverse clinical outcomes (ie, hospital admission, AIDS, and death) in children with vertical HIV-1 infection in Madrid, Spain

First case of homozygous C1 inhibitor deficiency.

Abstract: Background C1 Inhibitor (C1-Inh) deficiency causes angioedema and can be hereditary (HAE), caused by mutations in the C1-Inh gene (C1NH), or acquired (AAE). Patients with HAE show a complement profile different from that of patients with AAE with normal levels of C1 (C1q, C1r, and C1s). Objective We sought to characterize the complement profile of a patient with HAE and a mutation in homozygosis in the C1NH gene (c.1576T>G, Ile462Ser) and study his family. Methods Biochemical diagnosis of HAE was confirmed by analyzing the C1NH gene. Further studies on the levels and activation states of the C1q, C1r, C1s, and C1-Inh components of the classical pathway of complement activation were also performed. Results Another 7 members of the family were given diagnoses of HAE: 1 was homozygous and 6 were heterozygous for the C1NH mutation c.1576T>G. The homozygous patients showed undetectable C1q levels, reduced C1s levels, the circulating active form of C1r, and a C1-Inh mostly in its cleaved inactive form in plasma. Conclusion This is the first report of patients homozygous for a mutation affecting the coding region of C1NH. These patients showed a unique activation and consumption profile of the classical complement activation pathway different from that commonly observed in patients with HAE but similar to that of patients with AAE. Clinical implications The most common HAE treatment is attenuated androgens, which increase the C1NH gene transcription levels. Because the homozygous patients lack a wild-type allele, long-term prophylactic treatment with attenuated androgens might not be advisable.

Teratomas of the neck and mediastinum in children

Abstract: This retrospective study reviews a series of teratomas of the neck and mediastinum aiming at defining the features of these particular locations. We recorded prenatal diagnosis, perinatal management, clinical and radiologic features, pathology, surgical strategies and results in cervical and mediastinal teratomas treated over the last 10 years. During this period we treated 66 children with teratoma of which 11 (6 male and 5 female) had cervicomediastinal locations. Five babies had cervical teratomas extended into the anterior mediastinum in two cases. Prenatal diagnosis was made in three (two with polyhydramnios). Four babies were born by C-section and only one had a successful EXIT procedure. The diagnosis was confirmed by imaging and increased AFP. Surgical treatment involved total tumor removal and in one case subsequent removal of lymph node metastases. All children survived except one in whom airway could not be cleared at birth. Two children bear mild hypothyroidism. During the same period six patients aged 0-17 years were treated for mediastinal teratoma. Only one was prenatally diagnosed and only two had some dyspnea. Removal was performed either by median sternotomy, thoracotomy, or thoracoscopy. They all survive and are free of disease. Teratomas of the neck may cause fetal disease and unmanageable neonatal airway obstruction. Prenatal diagnosis and planned multidisciplinary management are mandatory at birth. In contrast, only some mediastinal tumors cause respiratory embarrassment. Although benign, these tumors are sometimes immature and may metastasize to regional lymph nodes. Total surgical removal is curative. Thyroid insufficiency may be present at birth in cervical teratomas and may be aggravated by surgery.

Metrifonate for Alzheimer's disease

Abstract: BACKGROUND Metrifonate is a long-acting irreversible cholinesterase inhibitor, originally used to treat schistosomiasis. Its potential to enhance central nervous system cholinergic neurotransmission led to clinical trials for the treatment of people with Alzheimer's disease (AD). Although low incidence of serious side effects occurred during short-term use as an antihelmintic, in studies of the treatment of AD extending over 6 months, 20 patients experienced respiratory paralysis and problems with neuromuscular transmission. These findings have led to a halt to trials of metrifonate for AD and Bayer, the pharmaceutical company, has withdrawn its FDA application. OBJECTIVES 1) To establish the efficacy of metrifonate for patients with Alzheimer's disease, in terms of cognition, global impression, functional activity, non cognitive symptoms, rate of institutionalization and mortality.2) Assess the safety and tolerability of metrifonate. SEARCH STRATEGY The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 5 December 2005 using the term metrifonat*. This Register is regularly updated with records from all major health care databases (MEDLINE, EMBASE, CINAHL, PsycINFO) and many trials databases. One of the authors (LS), as member of the Metrifonate Study Group has had the opportunity to contact other metrifonate trialists to obtain data from potentially non published data of metrifonate clinical trials. SELECTION CRITERIA All unconfounded, randomized double-blind clinical controlled trials comparing metrifonate to placebo in people with AD. DATA COLLECTION AND ANALYSIS Data were extracted by the two reviewers, cross-checked, and pooled when appropriate and possible. MAIN RESULTS Most studies assessed changes in cognitive function, global function, activities of daily living, behavioural problems, severity of disease and adverse events. Occasionally the results were not reported in sufficient detail to allow extraction of data for the meta-analyses. The treatment regimens were varied: loading doses were used in some trials. The range of maintenance doses and studies were not pooled unless the treatment regimens were considered comparable. The lengths of treatment varied from 6 to 26 weeks and studies were not pooled unless the treatment duration was similar. The results are derived from the ITT populations. Metrifonate at various doses, fixed and loading doses, was associated with significant cognitive improvement compared to placebo, except for weekly doses where there was no difference from placebo: MMSE (metrifonate 60-80 mg/day with initial loading at 26 weeks; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD 1.85, 95% CI 1.06 to 2.64, p<0.00001); ADAS-Cog (metrifonate 60-80 mg/day with initial loading at 26 weeks MD -3.24, 95% CI -4.40 to -2.08, p<0.00001)In most trials, there was improvement in clinical global impression: CIBIC-Plus (metrifonate 30-55 mg/day, approximately 0.65 mg/kg body weight, with initial loading at 26 weeks MD -0.25, 95% CI -0.41 to -0.09 p=0.002; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD -0.20, 95% CI -0.39 to -0.01, p=0.04). There were generally-significant drug-placebo differences in activities of daily living but this often depended on sample size and the characteristics of the instrument used: DAD (metrifonate 30-55 mg/day, 0.65 mg/kg body weight, with initial loading at 26 weeks MD 2.72, 95% CI 0.66 to 4.77, p=0.01; metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD 4.07, 95% CI 0.29 to 7.85, p=0.03)Also there were differences associated with metrifonate compared with placebo for different doses of metrifonate in scores on a behavioural symptom scale, caregiver burden scale, and severity of disease scale. Adverse events occurring more often with metrifonate included abdominal pain, bloating, bradycardia, diarrhoea, leg cramps, nausea and rhinitis and were described as mostly mild and transient, but occasionally moderately severe, and infrequently severe and serious. Analysis of the number of patients suffering at least one mild, moderate, severe or serious adverse event before the end of treatment showed that there was usually no difference between placebo and metrifonate. AUTHORS' CONCLUSIONS Metrifonate given once per day appears to be related to clinical response in cognition, global improvement, and activities of daily living in patients with mild to moderate Alzheimer's disease. Tolerability is good with adverse events as expected from a cholinesterase inhibitor, but with a low incidence of neuromuscular dysfunction and respiratory failure, too low to be detected in this review. It has been withdrawn from further development.

The haemophilic ankle.

Abstract: Summary. Radiation synoviorthesis is a very effective procedure that decreases both the frequency and the intensity of recurrent ankle bleeds related to ankle synovitis. The procedure should be performed as soon as possible to minimize the degree of articular cartilage damage. It can also be used in patients with inhibitors with minimal risk of complications. On average, the efficacy of the procedure ranges from 76% to 80%, and can be performed at any age. The procedure slows the cartilaginous damage which intra-articular blood tends to produce in the long term. After 30 years of using radiation synovectomy worldwide, no damage has been reported in relation to the radioactive materials. Radiation synovectomy is currently the preferred procedure when radioactive materials are available; however, chemical synoviorthesis is an effective alternative method if radioactive materials are not available. Personal experience and the general recommendation among orthopaedic surgeons and haematologists is that when three early consecutive synoviorthesis (repeated every 3 months) fail to halt synovitis, a surgical synovectomy (open or by arthroscopy) should be immediately considered. For advanced haemophilic arthropathy of the ankle, the best solution is an ankle arthrodesis. Primary prophylaxis and radioactive synoviorthesis are the best ways that we have today of protecting against haemophilic synovitis and arthropathy of the ankle joint.

Quality of life in postlingually deaf patients following cochlear implantation.

Abstract: Most cochlear implant studies are focused on improvement of speech perception associated with implantation. The goal of this study was to assess the impact of cochlear implantation on quality of life changes in Spanish users. Thirty postlingually deaf patients fitted with a cochlear implant completed the Glasgow Benefit Inventory, a questionnaire dealing with communication abilities, and an open-ended questionnaire. The Glasgow Benefit Inventory revealed a positive effect in 93% of patients. The use of a cochlear implant significantly enhanced discrimination ability, telephone use and self-confidence. A high degree of satisfaction was achieved in all situations except with background noise. Ninety-six percent of patients would recommend the operation to a friend. A dramatic improvement in quality of life following cochlear implantation is revealed by a great majority of patients. The results cannot only be explained by enhancements to auditory perception.

Impact of facial dysfunction on quality of life after vestibular schwannoma surgery.

Abstract: Objectives:This study was performed to evaluate the impact of facial dysfunction on quality of life in patients who underwent surgery for vestibular schwannoma. Other factors with a possible impact on quality of life were also assessed.Methods:We performed a retrospective review of 95 patients who underwent removal of a unilateral vestibular schwannoma. The Glasgow Benefit Inventory, an open-ended questionnaire, and a pain scale were sent to each patient. The questions were answered by 70 respondents (74%). After a minimum 1-year follow-up, the overall House-Brackmann postoperative facial function was grade I-II in 61% of patients, grade III-IV in 36%, and grade V-VI in 3%.Results:The open-ended questionnaire showed that 33% of patients stated a complaint related to facial dysfunction; it was the main complaint for 13% of patients. No significant difference was found in terms of Glasgow Benefit Inventory scores between patients with and without facial dysfunction, nor between those with different House-Br...

Analysis of IRF5 gene functional polymorphisms in rheumatoid arthritis.

Abstract: Objective Recent findings suggest that interferon regulatory factor 5 (IRF-5) may play a crucial role in several cellular processes, including the transcription of genes for inflammatory cytokines. Two genetic variants of the IRF5 gene (rs2004640 in exon 1 and rs2280714 in the 3′-untranslated region) have been shown to exert functional modifications affecting IRF5 messenger RNA splicing and expression, and have been associated with genetic predisposition to systemic lupus erythematosus (SLE). The aim of this study was to analyze the possible contribution of the IRF5 gene to the predisposition to rheumatoid arthritis (RA). Methods Three case–control cohorts from Spain (724 RA patients and 542 healthy controls), Sweden (281 RA patients 474 healthy controls), and Argentina (284 RA patients and 286 healthy controls) were independently analyzed. Genotyping for IRF5 rs2004640 and rs2280714 was performed using a TaqMan 5′ allele-discrimination assay. Results In the 3 cohorts studied, no statistically significant differences in allele or genotype frequencies of the rs2004640 and rs2280714 IRF5 polymorphisms were observed between RA patients and controls. Accordingly, haplotype analysis revealed that none of the IRF5 haplotypes was associated with genetic predisposition to RA. Conclusion Our results suggest that the IRF5 functional polymorphisms analyzed do not seem to be implicated in genetic susceptibility to RA.

Positron emission tomography/computed tomography: diagnostic accuracy in lymphoma.

Abstract: Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL) are clonal lymphoproliferative diseases that can present with different clinical manifestations that may be difficult to diagnose (Evans & Hancock, 2003; Re et al, 2005). The Ann Summary An accurate initial staging of patients with non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) is critical for the selection of an appropriate treatment. Computed tomography (CT) remains the standard imaging technique, although it is based on anatomic criteria. Positron emission tomography (PET) with 2-deoxy-2-(fluorine-18)fluoro-d-glucose (FDG) provides useful functional information but requires anatomical correlation to localise lesions accurately. We have prospectively compared the accuracy of combined PET/CT with that of CT and PET alone at initial staging in lymphoma patients. Forty-seven newly diagnosed patients were evaluated. PET/CT was superior compared with CT and PET in nodal evaluation and detection of extranodal disease. Using a staging algorithm with PET/CT resulted in the disease stage being increased in 11 of 47 patients (10 NHL and 1 HL) (McNemar test P ¼ 0AE012). Therefore, a different treatment strategy based on PET/CT findings was suggested for seven patients (14AE8%). PET/CT markedly improves accuracy in the diagnostic work-up of patients with lymphoma.

Regulatable gene expression systems for gene therapy

Abstract: It is feasible to restrict transgene expression to a tissue or region in need of therapy by using promoters that respond to focusable physical stimuli. The most extensively investigated promoters of this type are radiation-inducible promoters and heat shock protein gene promoters that can be activated by directed, transient heat. Temporal regulation of transgenes can be achieved by various two- or three-component gene switches that are triggered by an appropriate small molecule inducer. The most commonly considered gene switches that are reviewed herein are based on small molecule-responsive transactivators derived from bacterial tetracycline repressor, insect or mammalian steroid receptors, or mammalian FKBP12/FRAP. A new generation of gene switches combines a heat shock protein gene promoter and a small molecule-responsive gene switch and can provide for both spatial and temporal regulation of transgene activity.

Monitoring sedation in critically ill patients: bispectral index, Ramsay and observer scales

Abstract: SummaryBackground and objective:Sedation is commonly required by critically ill patients and inadequate sedation may be hazardous. Traditionally, subjective scales have been used for monitoring sedation. Bispectral index has been proposed, although its utility in the intensive care unit is debated.