Effective secondary fracture prevention: implementation of a global benchmarking of clinical quality using the IOF Capture the Fracture® Best Practice Framework tool.

UNLABELLED: Fracture Liaison Services are the best model to prevent secondary fractures. The International Osteoporosis Foundation developed a Best Practice Framework to provide a quality benchmark. After a year of implementation, we confirmed that a single framework with set criteria is able to benchmark services across healthcare systems worldwide. INTRODUCTION: Despite evidence for the clinical effectiveness of secondary fracture prevention, translation in the real-world setting remains disappointing. Where implemented, a wide variety of service models are used to deliver effective secondary fracture prevention. To support use of effective models of care across the globe, the International Osteoporosis Foundation's Capture the Fracture® programme developed a Best Practice Framework (BPF) tool of criteria and standards to provide a quality benchmark. We now report findings after the first 12 months of implementation. METHODS: A questionnaire for the BPF was created and made available to institutions on the Capture the Fracture website. Responses from institutions were used to assign gold, silver, bronze or black (insufficient) level of achievements mapped across five domains. Through an interactive process with the institution, a final score was determined and published on the Capture the Fracture website Fracture Liaison Service (FLS) map. RESULTS: Sixty hospitals across six continents submitted their questionnaires. The hospitals served populations from 20,000 to 15 million and were a mix of private and publicly funded. Each FLS managed 146 to 6200 fragility fracture patients per year with a total of 55,160 patients across all sites. Overall, 27 hospitals scored gold, 23 silver and 10 bronze. The pathway for the hip fracture patients had the highest proportion of gold grading while vertebral fracture the lowest. CONCLUSION: In the first 12 months, we have successfully tested the BPF tool in a range of health settings across the globe. Initial findings confirm a significant heterogeneity in service provision and highlight the importance of a global approach to ensure high quality secondary fracture prevention services.

Chromosomal characteristics of a Brazilian whip spider (Amblypygi) and evolutionary relationships with other arachnid orders.

We analyzed mitotic and meiotic cells of a Brazilian amblypygid, Heterophrynus longicornis, using conventional and molecular cytogenetic techniques (Giemsa staining, C-banding, Ag-NOR, and FISH with rDNA probe). This is the first study that focuses solely on amblypygid chromosomes; it was undertaken to add data on cytogenetic knowledge of this group and contribute to the understanding of chromosome evolution in the Arachnida. We found 2n = 66 for male and female individuals, monocentric chromosomes, and absence of morphologically differentiated sex chromosomes. C-banding showed heterochromatin in the pericentromeric region of most chromosomes. Mitotic and meiotic nuclei submitted to silver impregnation and FISH revealed, respectively, Ag-NORs and ribosomal genes in the terminal region of two chromosome pairs. Most chromosome features that we observed in H. longicornis are shared with species of other arachnid orders; however, the absence of morphologically differentiated sex chromosomes in amblypygid contrasts with the remarkable variety of sex chromosome systems recorded for the Araneae. Consequently, we conclude that analysis of species of the Tetrapulmonata clade is useful for understanding the trends of sex chromosome evolution in this arachnid group.

Chromosomal characteristics and karyotype evolution of Oxyopidae spiders (Araneae, Entelegynae).

We made a cytogenetic analysis of four species of Oxyopidae and compared it with the karyotype data of all species of this family. In Hamataliwa sp, the mitotic cells showed 2n♂ = 26+X(1)X(2) and telocentric chromosomes. The 2n♂ = 28, which has been described for only one oxyopid spider, is the highest diploid number reported for this family. Peucetia species exhibited distinct karyotype characteristics, i.e., 2n♂ = 20+X(1)X(2) in P. flava and 2n♂ = 20+X in P. rubrolineata, revealing interspecific chromosome variability within this genus. However, both Peucetia species exhibited telocentric chromosomes. The most unexpected karyotype was encountered in Oxyopes salticus, which presented 2n♂ = 10+X in most individuals and a predominance of biarmed chromosomes. Additionally, one male of the sample of O. salticus was heterozygous for a centric fusion that originated the first chromosomal pair and exhibited one supernumerary chromosome in some cells. Testicular nuclei of Hamataliwa sp and O. salticus revealed NORs on autosomal pairs, after silver impregnation. The majority of Oxyopidae spiders have their karyotype differentiated by both reduction in diploid number chromosome number and change of the sex chromosome system to X type; however, certain species retain the ancestral chromosome constitution 2n = 26+X1X2. The most remarkable karyotype differentiation occurred in O. salticus studied here, which showed the lowest diploid number ever observed in Oxyopidae and the second lowest registered for Entelegynae spiders.

Replication of viral RNA: RNA synthetase from Escherichia coli infected with phage MS2 or Qb.

An RNA synthetase is formed in Escherichia coli after infection with bacteriophages containing RNA. Specific annealing techniques revealed that, from the very outset of the reaction in vitro, the partially purified enzyme-template complex synthesizes parental-type plus strands, namely, MS2-RNA when isolated from cells infected with MS2 phage and Q(beta)-RNA in the case of cells infected with Q(beta) phage. This is in contrast to the situation found with Q(beta) replicase primed with Q(beta)-RNA, where the initial product is the complementary strand.

Intriguing evidence of translocations in Discus fish (Symphysodon, Cichlidae) and a report of the largest meiotic chromosomal chain observed in vertebrates.

As part of a program to understand the genetics of Amazonian ornamental fish, classical cytogenetics was used to analyze Symphysodon aequifasciatus, S. discus and S. haraldi, popular and expensive aquarium fishes that are endemic to the Amazon basin. Mitotic analyses in Symphysodon have shown some odd patterns compared with other Neotropical cichlids. We have confirmed that Symphysodon species are characterized by chromosomal diversity and meiotic complexity despite the fact that species share the same diploid number 2n=60. An intriguing meiotic chromosomal chain, with up to 20 elements during diplotene/diakinesis, was observed in S. aequifasciatus and S. haraldi, whereas S. discus only contains typical bivalent chromosomes. Such chromosomal chains with a high number of elements have not been observed in any other vertebrates. We showed that the meiotic chromosomal chain was not sex related. This observation is unusual and we propose that the origin of meiotic multiples in males and females is based on a series of translocations that involved heterochromatic regions after hybridization of ancestor wild Discus species.

Identification and localization of polycystin, the PKD1 gene product.

Polycystin, the product of autosomal dominant polycystic kidney disease (ADPKD) 1 gene (PKD1) is the cardinal member of a novel class of proteins. As a first step towards elucidating the function of polycystin and the pathogenesis of ADPKD, three types of information were collected in the current study: the subcellular localization of polycystin, the spatial and temporal distribution of the protein within normal tissues and the effects of ADPKD mutations on the pattern of expression in affected tissues. Antisera directed against a synthetic peptide and two recombinant proteins of different domains of polycystin revealed the presence of an approximately 400-kD protein (polycystin) in the membrane fractions of normal fetal, adult, and ADPKD kidneys. Immunohistological studies localized polycystin to renal tubular epithelia, hepatic bile ductules, and pancreatic ducts, all sites of cystic changes in ADPKD, as well as in tissues such as skin that are not known to be affected in ADPKD. By electron microscopy, polycystin was predominantly associated with plasma membranes. Polycystin was significantly less abundant in adult than in fetal epithelia. In contrast, polycystin was overexpressed in most, but not all, cysts in ADPKD kidneys.

Cytogenetic study in sand spiders (Sicariidae) from the brazilian Caatinga: sex chromosome system diversity in closely related species / Estudio citogenético en arañas de arena (Sicariidae) de la Caatinga brasileña: diversidad del sistema de cromosomas sexuales en especies estrechamente relacionadas

ABSTRACT In this study, we investigated the chromosomes of three species of Sicarius spiders from the Brazilian Caatinga, using classical and molecular cytogenetic techniques. Based on the phylogenetic approach, we also discussed about the variation of diploid number, types of sex chromosome system and changes in the localization of ribosomal genes of Scytodoidea. Sicarius are Synspermiata spiders that together with the genera Loxosceles and Hexophthalma constitute the family Sicariidae. In this group, the available cytogenetic data showed a low diploid number range (2n♂=18 to 2n♂=23) and the presence of only multiple sex chromosome systems (X1X2Y and X1X20). Mitotic metaphase cells exhibited 2n♂=16+X1X2Y for Sicarius cariri and S. ornatus, and 2n♂=18+XY for S. tropicus. In these species, silver impregnation revealed nucleolar organizer region (Ag-NOR) on the terminal region of pair 1. In S. ornatus and S. tropicus, the results obtained with fluorescent in situ hybridization (FISH) using 18S rDNA probe were similar to Ag-NOR, however in S. cariri, the ribosomal sites were localized in the terminal region of the X1 sex chromosome. In this work, we presented the first description of a simple sex chromosome system for Sicariidae, helping to understand how the XY sex chromosome system evolved from the X1X2Y system. Additionally, FISH data incongruous with Ag-NOR indicate that the cytogenetic studies in Sicariidae allow investigating the relation between the karyotype evolution and the distribution and the activity of rDNA genes.

RESUMEN En este estudio, investigamos los cromosomas de tres especies de arañas Sicarius de la Caatinga brasileña, utilizando técnicas de citogenética clásica y molecular. Usando un enfoque filogenético, también discutimos la variación del número diploide, los tipos de sistema cromosómico sexual y los cambios en la localización de los genes ribosómicos en Scytodoidea. Los Sicarius son arañas Synspermiata que, junto con los géneros Loxosceles y Hexophthalma, constituyen a la familia Sicariidae. En este grupo, los datos citogenéticos disponibles mostraron un rango de número diploide bajo (2n♂=18 a 2n♂=23) y únicamente la presencia de sistemas de cromosomas sexuales múltiples (X1X2Y y X1X20). Las células mitóticas en metafase mostraron 2n♂=16+X1X2Y para Sicarius cariri y S. ornatus, y 2n♂=18+XY para S. tropicus. En estas especies, la impregnación de plata reveló la región organizadora nucleolar (Ag-NOR) en la región terminal del par 1. En S. ornatus y S. tropicus, los resultados obtenidos con la hibridación in situ fluorescente (FISH) utilizando la sonda de ADNr 18S fueron similares a los de Ag-NOR, sin embargo, en S. cariri los sitios ribosomales se localizaron en la región terminal del cromosoma sexual X1. En este trabajo, presentamos la primera descripción de un sistema cromosómico sexual simple para Sicariidae, ayudando a entender cómo el sistema cromosómico sexual XY evolucionó a partir del sistema X1X2Y. Además, los datos de FISH incongruentes con Ag-NOR indican que los estudios citogenéticos en Sicariidae permiten investigar la relación entre la evolución del cariotipo y la distribución y la actividad de los genes de ADNr.

Oral misoprostol vs. intravenous oxytocin in reducing blood loss after emergency cesarean delivery.

OBJECTIVE: To compare the effectiveness of oral misoprostol and intravenous oxytocin in reducing blood loss in women undergoing indicated or elective cesarean delivery (CD) under spinal anesthesia. METHODS: In this prospective, double-blind pilot study, 56 parturients who received 5 IU of intravenous oxytocin after cord clamping were randomized to further receive either misoprostol orally and a placebo infusion intravenously or placebo orally and an oxytocin infusion intravenously. RESULTS: After adjustment was made for the sonographically estimated amniotic fluid volume, there was no statistical difference in blood loss between the 2 groups (mean+/-S.D., 1083+/-920 mL in the oxytocin group vs. 970+/-560 mL in the misoprostol group; P=.59). CONCLUSION: Oxytocin followed by oral misoprostol is as effective as an oxytocin injection followed by an oxytocin infusion in reducing postoperative blood loss after CD, and the protocol may be a safe, valuable, and cost-effective alternative to oxytocin alone. Visual estimation of intraoperative blood loss undervalues the effective value of misoprostol use by 30%.

Ropivacaine versus bupivacaine 0.125% with fentanyl 1 microg/ml for epidural labour analgesia: is daily practice more important than pharmaceutical choice?

UNLABELLED: Ropivacaine might be superior to bupivcaine for epidural labour analgesia because it appears to induce less lower extremity motor blockade. The clinical relevance of this difference is not yet clear. METHODS: In a double-blind randomised trial bupivacaine and ropivacaine each at 0.125% with 1 microg/ml fentanyl were compared for epidural labour analgesia. This study was performed in two university hospitals. RESULTS: Sixty-three nulliparous women with singleton pregnancies at term were included. There were no differences between bupivacaine and ropivacaine as far as motor blockade, analgesic outcome, mode of delivery and neonatal outcome are concerned. However, the clinical management of epidural analgesia differed significantly between the two institutions involved. Parturients of one institution had their epidural catheter placed earlier, needed less top-up medication, and had more successful mobilisations, when compared to the other institution. CONCLUSIONS: Institutional clinical practice can be significantly different. Pharmacological differences between bupivacaine and ropivacaine at 0.125% with 1 microg/ml fentanyl seem to be less important than differences between institutions in terms of clinical practice.

Overview of rabies in the Americas.

Between 1993 and 2002, the number of human and canine rabies cases in the Americas Region fell by approximately 80%. There were 39 human cases in 2002, 63% of them transmitted by dogs. Furthermore, human rabies transmitted by wildlife, mostly by bats is a risk to inhabitants in many countries in the Region. The objective of this study is to describe this epidemiological situation based in the information received from the countries of the Americas Region in Regional Rabies Surveillance System in the Americas (SIRVERA) administrated by the Pan American Health Organization. This sharp reduction is attributable mainly to the control measures implemented by the countries of the Region, such as the mass vaccination of dogs and prophylactic treatment for people who have been exposed.

Mild phenotype due to tandem duplication of l7p11.2.

We present a mildly affected girl with de novo dup(17)(p11.2p11.2). The patient was evaluated because of minor anomalies noted during a hospitalization for nonrecurrent tonic-clonic seizures associated with transient hypoglycemia. She also had unilateral renal hypoplasia and relative short stature, but at 2 years of age, she scored within the low normal range on neurodevelopmental examinations. Compared with other similar duplications, this patient represents the milder range of the spectrum for this karyotypic abnormality. Am. J. Med. Genet. 94:296-299, 2000.

Regulation of contraction-stimulated system A amino acid uptake in skeletal muscle: role of vicinal sulfhydryls.

Functional vicinal sulfhydryls are essential for insulin-stimulated system A neutral amino acid uptake in the rat epitrochlearis muscle. In skeletal muscle, system A uptake is also activated by contractile activity. Therefore, the purposes of this study were to characterize the stimulation of system A activity by contractions induced by electrical stimulation in vitro, and to assess the role of vicinal sulfhydryls in this process. System A activity in the isolated epitrochlearis muscle was measured using the nonmetabolizable analogue alpha-(methylamino)isobutyric acid (MeAIB). Contractions increased MeAIB uptake by increasing the apparent maximal velocity (Vmax), with no alteration in the apparent Km. The maximal stimulatory effects of insulin and contractions on MeAIB uptake were completely additive, demonstrating that these two stimuli exert their effects via different mechanisms. Phenylarsine oxide (PAO), a vicinal sulfhydryl antagonist, at greater than 20 mumol/L inhibited basal and contraction-stimulated MeAIB uptake by approximately 50% and 70%, respectively, by decreasing Vmax, with no change in Km. Both inhibitory effects were completely prevented by cotreatment with the vicinal dithiol dimercaptopropanol (DMP), indicating the effects were mediated by interactions with vicinal sulfhydryls. Contraction-stimulated MeAIB uptake was rapidly (half-time, approximately 7 minutes) reversed by the addition of PAO. These results (1) define conditions under which contraction-stimulated system A amino acid uptake can be studied in an isolated mammalian skeletal muscle preparation, and (2) indicate that vicinal sulfhydryls are essential for stimulation of system A activity by muscle contractions.

Potential force of infection of human rabies transmitted by vampire bats in the Amazonian region of Brazil.

Human rabies transmitted by bats has acquired greater epidemiologic relevance in various Latin American countries, just when cases transmitted by dogs have decreased. Concern has been heightened by reports of increased rates of bats biting humans in villages in the Amazonian region of Brazil. The aim of the present work was to estimate the potential force of infection (per capita rate at which susceptible individuals acquire infection) of human rabies transmitted by the common vampire bat if the rabies virus were to be introduced to a colony of bats close to a village with a high rate of human bites. The potential force of infection could be then used to anticipate the size of a rabies outbreak in control programs. We present an estimator of potential incidence, adapted from models for malaria. To obtain some of the parameters for the equation, a cross-sectional survey was conducted in Mina Nova, a village of gold prospectors in the Amazonian region of Brazil with high rates of bates biting humans. Bats were captured near dwellings and sent to The Rabies Diagnostic Laboratory at the Center for Control of Zoonoses (Sao Paulo, Brazil) to be examined. To estimate the force of infection, a hypothetical rabies outbreak among bats was simulated using the actual data obtained in the study area. Of 129 people interviewed, 23.33% had been attacked by a vampire bat during the year prior to the study, with an average of 2.8 bites per attacked person. Males (29.41%) were attacked more often than females (11.36%); also, adults (29.35%) were attacked more often than children (8.33%). None of the 12 bats captured in Mina Nova tested positive for rabies, but the force of infection for a hypothetical outbreak was estimated to be 0.0096 per person per year. This risk represents 0.96 cases per 100 area residents, giving an incidence of 1.54 cases of bat-transmitted human rabies per year in the village of Mina Nova (160 inhabitants). The estimated risk is comparable with what has been observed in similar Brazilian villages.

Mechanism of antinociceptive action of clonidine in nonmyelinated nerve fibres.

Despite a large body of clinical evidence in favour of a local anesthetic effect of clonidine, the underlying mechanism has not yet been elucidated. In this study we have used the sucrose-gap method to measure the effects of clonidine on the electrophysiological properties of nonmyelinated nerve fibers in the rabbit vagus nerve. The results showed that clonidine enhanced the hyperpolarizing and reduced the depolarizing afterpotential that follow compound action potentials during electrical activity. We showed that summation of these afterpotentials shifts the membrane potential toward more negative values, thus creating a region of low safety conduction, where the local circuit currents might fail to depolarize the axonal membrane to the threshold value needed to open voltage-dependent Na(+) channels. Yohimbine did not reverse the inhibitory effects of clonidine on impulse propagation, indicating that the observed effects of clonidine relies on mechanisms not mediated by alpha(2)-adrenoceptors.

Trends in infant mortality inequalities in the Americas: 1955-1995.

STUDY OBJECTIVE: s: To describe overall and income related trends in infant mortality inequalities in the Region of the Americas from 1955 to 1995. DESIGN: Infant mortality rates (IMRs) were computed and their trends assessed by ordinary least squares. Overall trends in IMR inequalities among countries were analysed by comparing 10 year period IMRs, Gini coefficients, and Lorenz curves. Income related trends in IMR inequalities were assessed using 10 year period IMR ratios between the highest and the lowest quintiles of the per capita gross national product (GNP) distributions (adjusted for purchasing power). SETTING: Aggregated country data were used for all countries with over 200 thousand inhabitants (33 geopolitical units). The 10 year period midpoint IMR estimates used for the 1955-1995 time series were those published by the United Nations in 1997. MAIN RESULTS: IMRs decreased from 90.34 to 31.31 per 1000 live births between 1955 and 1995 at an average of 15.3 every 10 years. In contrast, Lorenz curves and Gini coefficients were similar for the five 10 year periods. After grouping by adjusted GNP distribution, a similar decreasing trend of IMR was observed in all groups. The rate ratio between the group at the lowest quintile and that at the highest quintile ranged from 4 to 5. The analysis of variance for repeated observations showed that there is a significant reduction in the IMR (F=130.18; p<0.01), that trends did not differ significantly among groups (F=1.16; p=0.32), and that they were approximately linear (F=155.83; p<0.01). CONCLUSIONS: Despite a sizable reduction in the infant mortality, whether or not income related, levels of IMR inequality among countries have remained almost constant between 1955 and 1995 in the Region of the Americas. Further analysis and focused interventions are needed to tackle the challenges of reducing these persistent mortality inequalities.

Effects of intravenous lidocaine and/or esmolol on hemodynamic responses to laryngoscopy and intubation: a double-blind, controlled clinical trial.

STUDY OBJECTIVES: To evaluate the efficacy of intravenous lidocaine and two doses of esmolol for attenuating the cardiovascular responses to laryngoscopy and intubation, and to assess whether a combination of both drugs is more effective than either drug alone. DESIGN: Randomized, prospective, double-blind, placebo-controlled study. SETTING: University hospital. PATIENTS: 90 ASA status I and II normotensive women scheduled for elective gynecologic procedures with general anesthesia. INTERVENTIONS: Induction of anesthesia was standardized for all patients. The first group received lidocaine 1.5 mg/kg (Group LID); the second and third groups received esmolol 1 mg/kg and 2 mg/kg, respectively (Groups E1 and E2, respectively); the fourth group received lidocaine 1.5 mg/kg and esmolol 1 mg/kg (Group LID-E1); the fifth group received lidocaine 1.5 mg/kg and esmolol 2 mg/kg (Group LID-E2); the sixth group received saline as a placebo (Group PLAC). MEASUREMENTS AND MAIN RESULTS: Systolic blood pressure and heart rate (HR) were recorded before induction, before injection of the first test drug, immediately before laryngoscopy, and 1, 2, and 5 minutes following intubation. Duration of laryngoscopy was recorded. Only patients receiving placebo had increased HR values after intubation compared with baseline values (p < 0.05). The proportion of patients with a maximum HR exceeding 90 beats/min was significantly higher in the placebo group (8 of 15 patients) than in both esmolol groups (E1 2 of 15; E2 2 of 15) (p < 0.05). Systolic blood pressure values after tracheal intubation did not differ among groups except for those receiving the combinations of lidocaine and esmolol, and they had significantly lower blood pressure (BP) values compared with placebo (p < 0.05). CONCLUSIONS: Esmolol 1 to 2 mg/kg is reliably effective in attenuating HR response to tracheal intubation. Neither of the two doses of esmolol tested nor that of lidocaine affected the BP response. Only the combination of lidocaine and esmolol attenuated both HR and BP responses to tracheal intubation.

[Comments on models for studying human rabies outbreaks from bats]. / Reflexión sobre los modelos para el estudio de los brotes de rabia humana por murciélago.

This paper analyzes which of the possible public health models could contribute to an understanding of human rabies outbreaks transmitted by bats. First, we present a short review of the most common pertinent models. Second, we present an investigation of a human rabies outbreak transmitted by bats based on the socio-epidemiological model. The same outbreak is analyzed again using the complex system theory as a theoretical framework, as both a theoretical-practical exercise seeking an approximation to this theory and a model to study this problem.

Common vampire bat attacks on humans in a village of the Amazon region of Brazil.

Many people in Amazonian communities have reported bat bites in the last decade. Bites by vampire bats can potentially transmit rabies to humans. The objective of this study was to analyze factors associated with bat biting in one of these communities. A cross-sectional survey was conducted in a village of gold miners in the Amazonian region of Brazil (160 inhabitants). Bats were captured near people's houses and sent to a lab. Of 129 people interviewed, 41% had been attacked by a bat at least once, with 92% of the bites located on the lower limbs. A logistic regression found that adults were bitten around four times more often than children (OR = 3.75, CI 95%: 1.46-9.62, p = 0.036). Males were bitten more frequently than females (OR = 2.08, CI 95%: 0.90-4.76, p = 0.067). Nine Desmodus rotundus and three frugivorous bats were captured and tested negative for rabies. The study suggests that, in an area of gold miners, common vampire bats are more likely to attack adults and males. The control strategy for human rabies developed in this region should therefore place special emphasis on adult males. There should also be more research on how the search for gold in the Amazonian region places people and the environment at risk.

[Treatment of human rabies: a summary of its history]. / Tratamiento contra la rabia humana: un poco de su historia.

A historical review of the treatment of human rabies from ancient times up to the present is undertaken. An attempt is made to trace parallel between the concept of the main cause of rabies in a certain period and the kind of treatment utilized. The ancient Greek goddess Artemis was considered to be a healer of rabies; they already identified wound cauterization. People of the first century A.D. knew of the infection deriving from the saliva of a rabid dog and called it virus (in Latin). During medieval times when a magical and religious concept regarding health was prevalent, the principal protector was called St. Humbert. During the Renaissance many experiments were carried out and new information on the disease was obtained, both were basic in opening the way for new findings in the future. At that time the miasmatic and contagious theories were predominant. Pasteur strongly objected to the idea of the spontaneity of rabies. At the end of the XIXth. century and based on microbial discoveries, Pasteur brought about a great scientific revolution as regards the possibility of treating rabies by using a vaccine. At the present time, vaccines are of the nervous type or not, and the recommended dose varies. A large-number of studies on vaccination have been undertaken. In Latin America the most used are those by Fuenzalida and Palacios. At present, WHO recommends the vaccine made by cell culture.