Dabigatran: A new oral anticoagulant. Guidelines to follow in oral surgery procedures. A systematic review of the literature.

BACKGROUND: Dabigatran is a newly commercialized drug that is replacing other anticoagulants in the prevention of venous thromboembolism, stroke and systemic arterial valve embolism. It acts directly on thrombin presenting in a dynamic and predictable way, which does not require monitoring these patients. Therefore, we consider the need to assess whether their use increases the risk of bleeding involved before any dental treatment. MATERIAL AND METHODS: We performed a systematic review with a bibliographic search in PubMed/Medline along with the Cochrane Library. We excluded articles dealing with all anticoagulants other than dabigatran, and works about surgical treatments in anatomical locations other than the oral cavity. RESULTS: We included a total of 13 papers of which 1 was a randomized clinical trial, 9 narrative literature reviews, 1 case series, 2 clinical cases and 1 expert opinion. Because we did not obtain any properly designed clinical trials, we were unable to conduct a meta-analysis. CONCLUSIONS: Currently, there is no consensus on the procedure to be followed in patients taking dabigatran. However, all authors agree to treat each case individually in accordance to the risk of embolism, postoperative bleeding and renal function. Also, it is necessary to perform minimally invasive interventions, and take the appropriate local anti-hemolytic measures.

The use of piezoelectric surgery to lateralize the inferior alveolar nerve with simultaneous implant placement and immediate buccal cortical bone repositioning: a prospective clinical study.

A prospective study was conducted to assess a variation of inferior alveolar nerve (IAN) lateralization. This study included 13 patients. An osteotomy was made with a piezoelectric device, and the IAN bundle was moved buccally. Dental implants were then inserted medial to the nerve bundle, and the inner surface of the buccal cortical bone plate was shaped to reduce its thickness. Finally, the bone plate was repositioned to restore the original shape and contour of the mandible. Neurosensory examinations of the lower lip and chin were performed using three tests: light touch, pain, and two-point discrimination. Three months after surgery, the function of the IAN was judged to be completely restored at 11 of the 13 surgical sites. Differences in the tests comparing the operated and non-operated sides were not significant. No implants were lost, and all patients were satisfied with the result. Although IAN lateralization in conjunction with dental implant placement is rarely indicated, the use of a piezoelectric device to perform a buccal osteotomy with final repositioning of the buccal cortical plate over the bony defect contributes to the recovery of the contour and shape of the mandible, without impairment of IAN function.

Altered visual sensory fusion in children with reading difficulties.

Reading is a multi-sensory and multi-cognitive task, and its difficulties (e.g., dyslexia) are not a unitary disorder. There are probably a variety of manifestations that relate to the actual site of impairment. A randomized, pre-test/post-test nonequivalent-groups design was conducted over 4 months with three groups aged between 6 and 8 years. One group comprised 76 participants (34 boys, 42 girls) with reading difficulties and altered sensory fusion (RD+ASF), a second group was made up of 123 students (59 boys, 64 girls) with reading difficulties but without altered sensory fusion (RD), and a third group comprised 81 participants (39 boys, 42 girls) who were young readers (RL) without reading delay, paired with the RD group on reading level. The experimental groups received intervention in the skills of control, stimulus recognition, and phonological awareness during a 4-month period. Both pre-test and post-test measures of errors in reading mechanics and reading routes (word and pseudo-word) were obtained. Poorer results in mechanics and reading routes of the RD+ASF group suggest that the effectiveness of the intervention depended on the characteristics of the groups and on the presence of sensory fusion deficits in the RD students.

[Anaesthetic implications in a pregnant patient with an extreme thrombocytopenia due to a May-Hegglin anomaly: general o regional anaesthesia?]. / Implicaciones anestésicas en gestante con trombocitopenia extrema por síndrome de May-Hegglin: ¿anestesia regional o general?

The May-Hegglin anomaly is an inherited disorder, so uncommon that the incidence is still unknown. It is characterized by macro-thrombocytopenia with normal platelet function and cytoplasmic inclusion bodies in granulocytes. The case is reported of a 28-year-old primiparous patient who had an urgent caesarean section due to failed induction of labour. The patient had no history of abnormal bleeding. Other causes of thrombocytopenia or platelet dysfunction, such as preeclampsia, HELLP syndrome, or placental abruption, were ruled out. The platelet count prior to surgery was 20,900/mm(3) with normal platelet function. General anaesthesia was performed. No excessive bleeding occurred and a platelet transfusion was not needed.

Spatial memory extinction: a c-Fos protein mapping study.

While the neuronal basis of spatial memory consolidation has been thoroughly studied, the substrates mediating the process of extinction remain largely unknown. This study aimed to evaluate the functional contribution of selected brain regions during the extinction of a previously acquired spatial memory task in the Morris water maze. For that purpose, we used adult male Wistar rats trained in a spatial reference memory task. Learning-related changes in c-Fos inmunoreactive cells after training were evaluated in cortical and subcortical regions. Results show that removal of the hidden platform in the water maze induced extinction of the previously reinforced escape behavior after 16 trials, without spontaneous recovery 24h later. Extinction was related with significantly higher numbers of c-Fos positive nuclei in amygdala nuclei and prefrontal cortex. On the other hand, the lateral mammillary bodies showed higher number of c-Fos positive cells than the control group. Therefore, in contrast with the results obtained in studies of classical conditioning, we show the involvement of diencephalic structures mediating this kind of learning. In summary, our findings suggest that medial prefrontal cortex, the amygdala complex and diencephalic structures like the lateral mammillary nuclei are relevant for the extinction of spatial memory.

[Hip arthroplasty with conventional stem as rescue treatment after failed treatment of intertrochanteric hip fractures]. / Artroplastia de cadera con vástago convencional en fracasos de osteosíntesis de fracturas del fémur proximal.

OBJECTIVE: The purpose of this study is to evaluate the results and complications of hip arthroplasty with conventional stem performed as a salvage procedure after the failed treatment of an intertrochanteric hip fracture. MATERIAL AND METHODS: Between 1997 and 2011, 17 patients with a mean age of 76 years were treated with hip arthroplasty for failed treatment of intertrochanteric hip fracture. In all cases a conventional stem was used. The mean follow-up was 6 years (range 1-14 years). Pain, range of motion (Merle d'Aubigné) and functional results (Barthel), as well as implant fixation (Harris and Engh), were evaluated during the follow-up. RESULTS: Except for one case of death (6%) and one case of infection (Girdlestone arthroplasty), all patients were able to walk independently at 6 months. The majority of the patients (87%) had no or mild pain. After 2 surgeries (osteosynthesis and hip arthroplasty) the mean Barthel Score had decreased from 81 to 66 points. Just one case (6%) of stem loosening has been observed. DISCUSSION: In older patients, prosthetic replacement after failed proximal femoral fixation is a reliable salvage option. Most patients have good pain relief and functional improvement, although the rate of perioperative medical complications is high. Surgery is less demanding and the operating time is shorter when conventional femoral stems are used.

Comparison of Modern Methods for Analyzing Repeated Measures Data With Missing Values.

Missing data are a pervasive problem in many psychological applications in the real world. In this article we study the impact of dropout on the operational characteristics of several approaches that can be easily implemented with commercially available software. These approaches include the covariance pattern model based on an unstructured covariance matrix (CPM-U) and the true covariance matrix (CPM-T), multiple imputation-based generalized estimating equations (MI-GEE), and weighted generalized estimating equations (WGEE). Under the missing at random mechanism, the MI-GEE approach was always robust. The CPM-T and CPM-U methods were also able to control the error rates provided that certain minimum sample size requirements were met, whereas the WGEE was more prone to inflated error rates. In contrast, under the missing not at random mechanism, all evaluated approaches were generally invalid. Our results also indicate that the CPM methods were more powerful than the MI-GEE and WGEE methods and their superiority was often substantial. Furthermore, we note that little or no power was sacrificed by using CPM-U method in place of CPM-T, although both methods have less power in situations where some participants have incomplete data. Some aspects of the CPM-U and MI-GEE methods are illustrated using real data from 2 previously published data sets. The first data set comes from a randomized study of AIDS patients with advanced immune suppression, the second from a cohort of patients with schizotypal personality disorder enrolled in a prevention program for psychosis.

Triatominae-Trypanosoma cruzi/T. rangeli: Vector-parasite interactions.

Of the currently known 140 species in the family Reduviidae, subfamily Triatominae, those which are most important as vectors of the aetiologic agent of Chagas disease, Trypanosoma cruzi, belong to the tribes Triatomini and Rhodniini. The latter not only transmit T. cruzi but also Trypanosoma rangeli, which is considered apathogenic for the mammalian host but can be pathogenic for the vectors. Using different molecular methods, two main lineages of T. cruzi have been classified, T. cruzi I and T. cruzi II. Within T. cruzi II, five subdivisions are recognized, T. cruzi IIa-IIe, according to the variability of the ribosomal subunits 24Salpha rRNA and 18S rRNA. In T. rangeli, differences in the organization of the kinetoplast DNA separate two forms denoted T. rangeli KP1+ and KP1-, although differences in the intergenic mini-exon gene and of the small subunit rRNA (SSU rRNA) suggest four subpopulations denoted T. rangeli A, B, C and D. The interactions of these subpopulations of the trypanosomes with different species and populations of Triatominae determine the epidemiology of the human-infecting trypanosomes in Latin America. Often, specific subpopulations of the trypanosomes are transmitted by specific vectors in a particular geographic area. Studies centered on trypanosome-triatomine interaction may allow identification of co-evolutionary processes, which, in turn, could consolidate hypotheses of the evolution and the distribution of T. cruzi/T. rangeli-vectors in America, and they may help to identify the mechanisms that either facilitate or impede the transmission of the parasites in different vector species. Such mechanisms seem to involve intestinal bacteria, especially the symbionts which are needed by the triatomines to complete nymphal development and to produce eggs. Development of the symbionts is regulated by the vector. T. cruzi and T. rangeli interfere with this system and induce the production of antibacterial substances. Whereas T. cruzi is only subpathogenic for the insect host, T. rangeli strongly affects species of the genus Rhodnius and this pathogenicity seems based on a reduction of the number of symbionts.

Development of lymphoproliferative disease after liver transplantation.

INTRODUCTION: Malignancies are a serious long-term complication among liver transplant recipients, with an overall incidence of 4.5%-15%. Posttransplantation lymphoproliferative disease (PTLD) is one of the leading causes of late death. Its development is related to complex interactions between immunosuppressive drugs and environmental agents. The aim of this study was to analyze risk factors for PTLD and survival after orthotopic liver transplantation (OLT) compared with solid tumors. PATIENTS AND METHODS: We undertook a retrospective review of the clinical histories of adult patients who underwent OLT between July 1986 and February 2001, and who had been followed until 2005. This study comprised 528 adult recipients who survived more than 2 months after OLT. We excluded pediatric, partial-organ, and multiorgan recipients. RESULTS: No differences were observed concerning gender, viral etiology of hepatitis, calcineurin inhibitor regimen, or steroid maintenance period. Treated acute rejection episodes accounted for 53.3% of patients who developed PTLD compared with 47.3% in the control group (P = .787). Patients with solid tumors were older at the time of diagnosis than those with PTLD (57.5 +/- 8.13 years vs 48.8 +/- 13.9; P = .002). The overall mortality rate for PTLD was 55.5%, which did not differ significantly from solid tumors. CONCLUSIONS: PTLD develops in younger patients after OLT. Various immunosuppressive regimens do not seem to influence the incidence of PTLD or other solid tumors.

[Ways of physical and symbolic isolation: leprosy, its isolation spaces and the medical-legal discourse in Argentina]. / Formas de aislamiento físico y simbólico: la lepra, sus espacios de reclusión y el discurso médico-legal en Argentina.

During the first half of the twentieth century, the presence of leprosy in modern societies provoked various reactions. As ancient prejudices had not disappeared yet, the medical-legal discourse dealt with a problem that exceeded the strictly sanitary framework. From a scientific perspective, this paper analyzes the way in which answers find that seemed the population and the future of the race in the physical and symbolic isolation of the leper, were developed in Argentina. In that context, the eugenics legitimated strong restrictions of rights to sick persons on whom this ancestral stigma continued to carry much weight.

Changes in brain oxidative metabolism induced by water maze training.

Although the hippocampus has been shown to be essential for spatial memory, the contribution of associated brain regions is not well established. Wistar rats were trained to find a hidden escape platform in the water maze during eight days. Following training, the oxidative metabolism in different brain regions was evaluated using cytochrome oxidase histochemistry. Metabolic activations were found in the prelimbic cortex, cornu ammonis (CA) 1 subfield of the dorsal hippocampus and the anterior thalamic nuclei, relative to yoked swim controls and naïve rats. In addition, many cross-correlations in brain metabolism were observed among the latter regions. These results support the implication of a hippocampal-prefrontal-thalamic system to spatial memory in rats.

Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity.

N-acetyltransferase 2 (NAT2), an important enzyme in clinical pharmacology, metabolizes antibiotics such as isoniazid and sulfamethoxazole, and catalyzes the transformation of aromatic and heterocyclic amines from the environment and diet into carcinogenic intermediates. Polymorphisms in NAT2 account for variability in the acetylator phenotype and the pharmacokinetics of metabolized drugs. Native Americans, settled in rural areas and large cities of Latin America, are under-represented in pharmacogenetics studies; therefore, we sequenced the coding region of NAT2 in 456 chromosomes from 13 populations from the Americas, and two from Siberia, detecting nine substitutions and 11 haplotypes. Variants *4 (37%), *5B (23%) and *7B (24%) showed high frequencies. Average frequencies of fast, intermediate and slow acetylators across Native Americans were 18, 56 and 25%, respectively. NAT2 intra-population genetic diversity for Native Americans is higher than East Asians and similar to the rest of the world, and NAT2 variants are homogeneously distributed across native populations of the continent.

Factors affecting strontium absorption in drownings.

This study examines the effects of age, gender, a cold water medium versus warm water medium, and salinity on strontium levels determined in left ventricular blood in drownings. Significant differences in the amount of strontium absorbed into the bloodstream (p<0.001) were detected between individuals who drowned in fresh water versus those drowning in seawater, and between those drowning in cold water versus warm water (p=0.030). However, no significant differences were noted in the strontium concentrations of left ventricular blood according to gender or age.

Comparison between lung weight and blood strontium in bodies found in seawater.

This paper examines the use of lung weight increase as an indicator of seawater drowning compared to the amount of Sr absorbed by the blood. The study population was limited to male victims older than 20 years. Significant differences between cases of drowning and "non-drowning" were detected in terms of the lung-heart weight ratio (L/H) (p<0.001) or lung-body weight ratio (L/B) (p=0.005). However, using lung weight (L), L/H or L/B to distinguish between seawater drownings and saltwater non-drownings some overlap was produced. The factor rendering least overlap was L/B, which also appeared to be non-dependent on the victim's age. Our findings suggest that a value of L/B higher than 19.5 g/kg could be a useful indicator of death by drowning, but that when a lower value is found, additional drowning diagnoses would be needed to establish the manner of death.

Virological analysis in the diagnosis of sudden children death: a medico-legal approach.

Infections are considered to be an important cause of unexpected death in children. It has also been assumed that respiratory viruses are involved in the genesis of sudden infant death syndrome (SIDS). The Spanish National Institute of Toxicology and Forensic Sciences act as the forensic reference centre for Spain. We analyse the experience of this centre in the virological study of 64 cases of sudden children death where viral serology, virological cultures, herpesviruses polymerase chain reaction (PCR) and electron microscopy were performed. According to pathological findings, death could only be attributed to an adenovirus infection in one amygdalitis with upper airways stenosis and asphyxia. Human herpes virus 6 (HHV-6) was detected by PCR in one case with pathological findings characteristic of SIDS. Recent infection by respiratory syncytial virus (RSV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were also detected. Meanwhile, 85.9% of the cases yielded negative viral results. Twenty-eight infants were finally categorised as SIDS. Pathological findings of infection were detected in 12 patients despite the negativity of viral analyses. Although viral infection is an uncommon cause of sudden children death, a complete microbiological investigation will help to solve the puzzle of SIDS. Definitive guidelines for microbiological analyses need to be updated whilst new pathogens are discovered or new techniques are implemented in order to clarify unsolved cases.

[Comparison between the 1993 and 2002 Guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) for identifying respiratory events in polysomnography tests]. / Comparación entre las normativas de la SEPAR de 1993 y 2002 en la lectura de los eventos respiratorios de las mismas polisomnografías.

OBJECTIVE: To compare the results of applying both the 1993 and 2002 guidelines of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) to identify respiratory events during nighttime polysomnography tests. PATIENTS AND METHODS: One hundred twenty consecutive patients with medium to high suspicion of sleep apnea-hypopnea syndrome (SAHS) were included in the study. The 1993 guidelines recommended the use of a thermistor and the evaluation of only apneas and hypopneas. The 2002 guidelines, on the other hand, recommended the use of a thermistor, nasal pressure cannula, and thoracoabdominal bands so that respiratory effort related to arousals could be studied along with apneas and hypopneas. In our study we did not use an esophageal pressure catheter. We calculated the apnea index, hypopnea index, and apnea-hypopnea index (AHI) and determined the number of patients who would be diagnosed with SAHS (AH I > or =10) and the number for whom initiation of continuous positive airway pressure treatment would be recommended (AHI > or =30) according to the 2 sets of guidelines. RESULTS: Polysomnographic tests were valid for 118 of the 120 patients (80% men). The mean (SD) age was 51 (11.6) years and the mean body mass index 31.2 (4.3). Using the 1993 guidelines, the AHI was less than 10 in 25 patients, between 20 and 29 in 38, and 30 or more in 50. In the group overall, mean apnea and hypopnea indices and AHI were all significantly higher with the 2002 guidelines than with the 1993 criteria. With the 1993 criteria, the mean AHI was 33.16 and with 2002 criteria, 45.02 (P<.05). Sixty-four percent of the studies considered normal according to the 1993 SEPAR guidelines were considered apneic according to the 2002 guidelines. Of the patients considered not to need continuous positive airway pressure according to the 1993 SEPAR guidelines, 47.61% did need therapy according to the 2002 guidelines. CONCLUSIONS: There are significant differences in AHI, and in both apnea and hypopnea indices depending on whether the 1993 or the 2002 SEPAR guidelines are applied.

Mutation rates at Y chromosome specific microsatellites.

A collaborative work was carried out by the Spanish and Portuguese ISFG Working Group (GEP-ISFG) to estimate Y-STR mutation rates. Seventeen Y chromosome STR loci (DYS19, DYS385, DYS389I and II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS460, DYS461, DYS635 [GATA C4], GATA H4, and GATA A10) were analyzed in a sample of 3,026 father/son pairs. Among 27,029 allele transfers, 54 mutations were observed, with an overall mutation rate across the 17 loci of 1.998 x 10(-3) (95% CI, 1.501 x 10(-3) to 2.606 x 10(-3)). With just one exception, all of the mutations were single-step, and they were observed only once per gametogenesis. Repeat gains were more frequent than losses, longer alleles were found to be more mutable, and the mutation rate seemed to increase with the father's age. Hum Mutat 26(6), 520-528, 2005. (c) 2005 Wiley-Liss, Inc.

Molecular characterisation of Trypanosoma rangeli strains isolated from Rhodnius ecuadoriensis in Peru, R. colombiensis in Colombia and R. pallescens in Panama, supports a co-evolutionary association between parasites and vectors.

We present data on the molecular characterisation of strains of Trypanosoma rangeli isolated from naturally infected Rhodnius ecuadoriensis in Peru, from Rhodnius colombiensis, Rhodnius pallescens and Rhodnius prolixus in Colombia, and from Rhodnius pallescens in Panama. Strain characterisation involved a duplex PCR with S35/S36/KP1L primers. Mini-exon gene analysis was also carried out using TrINT-1/TrINT-2 oligonucleotides. kDNA and mini-exon amplification indicated dimorphism within both DNA sequences: (i) KP1, KP2 and KP3 or (ii) KP2 and KP3 products for kDNA, and 380 bp or 340 bp products for the mini-exon. All T. rangeli strains isolated from R. prolixus presented KP1, KP2 and KP3 products with the 340 bp mini-exon product. By contrast, all T. rangeli strains isolated from R. ecuadoriensis, R. pallescens and R. colombiensis, presented profiles with KP2 and KP3 kDNA products and the 380 bp mini-exon product. Combined with other studies, these results provide evidence of co-evolution of T. rangeli strains associated with different Rhodnius species groups east and west of the Andean mountains.

Latex agglutination for bacterial antigens and meningococcus PCR: two useful tools in legal sudden deaths.

Bacterial infections are considered to be a major cause of sudden deaths. The recognition of infections caused by Neisseria meningitidis is an essential duty of medicolegal offices due to the risk of secondary cases. Since other microorganisms, such as Haemophilus influenzae and Streptococcus pneumoniae, are also involved in infectious sudden deaths, the identification of the pathogen responsible for death is essential in order to establish a positive diagnosis while also preventing secondary meningococcal cases. However, because of the unreliability of culture methods used for autopsy specimens and the fragile nature of the microorganisms, other techniques were used. In this study, the detection of specific antigens of N. meningitidis (serogroups A, B, C, Y and W135), H. influenzae type b, S. pneumoniae and Group B Streptococcus was undertaken in 40 samples from sudden death cases in legal procedures with a latex agglutination test. In addition, a meningococcus polymerase chain reaction (PCR) assay (ctrA, crgA and siaD genes) was also used as a corroboration method for positive N. meningitidis agglutinations. Eleven cases of sudden death were confirmed to be due to meningococcus while one case was confirmed to have been caused by H. influenzae type b fulminant epiglottitis. Rapid laboratory diagnosis of meningococcal infection allowed contacts management and notification to the health authorities. From the point of view of the authors, forensic diagnosis of unascertained deaths should include latex agglutination and meningococcus PCR when a fulminant infection by N. meningitidis or H. influenzae is suspected as well as in deaths where the cause is unclear.