Twin sisters, monozygotic with the fragile X mutation, but with a different phenotype.

The absence of the fragile X mental retardation protein (FMRP) results in fragile X syndrome. All males with a full mutation in the FMR1 gene and an inactive FMR1 gene are mentally retarded while 60% of the females with a full mutation are affected. Here we describe monozygotic twin sisters who both have a full mutation in their FMR1 gene, one of whom is normal while the other is affected. Using molecular and protein studies it was shown that owing to preferential X inactivation in the affected female a minority of the cells expressed the normal FMR1 gene, while in her sister most cells expressed the normal FMR1 gene. This shows that X inactivation took place in the female twins after separation of the embryos and that for a normal phenotype FMR1 expression is necessary in the majority of cells.

Coping strategies and postpartum depressive symptoms: A structural equation modelling approach.

BACKGROUND: Variables such as the mother's personality, social support, coping strategies and stressful events have been described as risk factors for postpartum depression. Structural Equation Modelling (SEM) analysis was used to examine whether neuroticism, perceived social support, perceived life events, and coping strategies are associated with postpartum depressive symptoms at the 8th and 32nd weeks. METHODS: A total of 1626 pregnant women participated in a longitudinal study. Different evaluations were performed 8 and 32weeks after delivery. Several measures were used: the Edinburgh Postnatal Depression Scale (EPDS), the Diagnostic Interview for Genetic Studies (DIGS), the Eysenck Personality Questionnaire (EPQ-RS), the St. Paul Ramsey life events scale and the Duke-UNC Functional Social Support Questionnaire. The brief COPE scale was used to measure coping strategies. SEM analysis was conducted for all women and in those women with a clinical diagnosis of postpartum depression. RESULTS: Passive coping strategies were associated with postpartum depressive symptoms at both visits (8th and 32nd weeks). Neuroticism was associated with more passive coping strategies and less active coping strategies. Neuroticism and life stress were positively correlated, and social support was negatively correlated with life stress and neuroticism. CONCLUSIONS: Early identification of potential risk for symptomatology of depression postpartum should include assessment of neuroticism, life events, social support and coping strategies.

Snoring and myocardial infarction: a 4-year follow-up study.

The association between snoring and myocardial infarction was studied in 1453 people of both sexes aged 20-70 years. The study was carried out in a population of 92,364 residents and the subjects were recruited using the Electoral Census. A questionnaire was sent to all participants, asking about snoring and cardiovascular risk factors. Hospital records were checked for the next 4 years to establish how many of them developed myocardial infarction. At the beginning of the follow-up study 39 patients were diagnosed with ischaemic heart disease. Of the other 1414 participants, 571 (40.4%) were snorers and 843 (59.6%) non-snorers. Twenty-one developed myocardial infarction in the snorer group and four in the non-snorer group. The snorer group presents an adjusted relative risk of myocardial infarction of 3.08 (95% CI 1.01-9.46) with respect to non-snorers. We conclude that snoring seems to be a potential risk factor for myocardial infarction.

[Symptoms of sleep apnea syndrome in the general population]. / Sintomatología del síndrome de apnea del sueño en la población general.

The aim of this study was to determine the clinical features of patients with sleep apnea syndrome (SAS) in the general population. One hundred ten individuals were selected randomly from the census and given hospital appointments. Case histories were taken and complete physical examinations were made. Nighttime respiratory polysomnograms were performed. Twenty-two (20%) of the 110 subjects presented SAS. In the SAS group, 59.1% were habitual snorers and 22.7% reported daytime hypersomnolence. The SAS patients has a mean age of 59.6 +/- 8.8 years and 45.4% showed alterations of the pharynx. No differences in spirometric variables were observed. Only age and daytime hypersomnolence predicted SAS in the multivariate analysis. We conclude that the prevalence of snoring, daytime hypersomnolence, pharyngeal alterations are higher in patients with SAS. The patients are also older. Only age and daytime hypersomnolence predicted of SAS.

[Experimental therapeutic models for fragile X syndrome]. / Modelos terapéuticos experimentales en el síndrome X frágil.

Fragile X syndrome is the most frequent form of familial mental retardation. The disease is caused by the absence of the function of the FMR1 gene product (FMRP). FMRP is a mRNA binding protein but the mechanism by which FMRP inactivation leads to the cognitive deficits in fragile X patients is still unknown. There is no effective specific treatment for the disease. The genetics of the fragile X syndrome suggest that gene therapy may eventually be able to provide a cure for the disease. However several different approaches are also being investigated by many different research laboratories. The search for an effective therapy for fragile X patients will be facilitated by a better understanding of the pathophysiology of the disease. This requires research into many different areas of biology including protein replacement therapy, gene reactivation, transcriptional regulation, neuronal activity enhancement and neuroprotection, nutritional intervention, regulation of neurotransmission and synapse regeneration. All these approaches can be investigated using animal models of the fragile X syndrome, before being used to develop effective treatment for fragile X patients. Although there is still no cure for the fragile X syndrome, the symptoms of the disease can be treated using an integrated approach where the different interventions are supported by a specific team. All of these approaches are providing new insights into both the treatment of fragile X patients and our understanding of the pathophysiology of the disease. Until a cure is found, an integrated approach to intervention is the best way to minimise or avoid some of the manifestations associated with the fragile X syndrome.

[The clinical characteristics of pulmonary tuberculosis in the elderly]. / Características clínicas de la tuberculosis pulmonar en el anciano.

Pulmonary tuberculosis remains as a significant clinical problem in the elderly. To describe age-related differences in disease manifestations, a comparison was made taking in consideration predisposing factors, clinical features, radiographic findings and diagnostic approaches in cases of pulmonary tuberculosis between two groups: equal o higher of 60 years and lower of 60 years. Elderly patients had a higher number of antecedents of previous tuberculosis and underlying diseases than younger patients. At admission, symptoms like fever and hemoptysis were more frequent in the younger group. Radiographic findings revealed that upper lung infiltrates were still common in both groups, and that elderly patients presented less pleural effusions and cavitary lesions than younger patients. Since there were differences in the clinical presentations of pulmonary tuberculosis in the elderly group, a high index of suspicion for the disease should be maintained.

[Most common cardiovascular diseases and sleep apnea syndrome. A general population study]. / Enfermedades cardiovasculares más frecuentes y síndrome de apnea del sueño. Un estudio en población general.

BACKGROUND: The sleep apnea syndrome (SAS) is a frequent disease associated with significant morbidity. The aim of our study was to investigate diseases associated with the sleep apnea syndrome (SAS) in general population. METHODS: We selected a random sample of 110 people from the electoral census. These people were invited to the clinic where medical history, physical examination and monitoring for sleep-disordered breathing was done. RESULTS: Twenty two subjects were diagnosed of SAS. The prevalence of arterial hypertension in the SAS group was 36.4%, and coronary artery disease 13.6%. CONCLUSIONS: Although the prevalence of this diseases was increased in the SAS group, we do not see significant association with this disease.

[Epidemiological study of tuberculosis in the health area of Santiago de Compostella in 1992, 1993 and 1994]. / Estudio epidemiológico de la tuberculosis en el área sanitaria de Santiago de Compostela durante 1992, 1993 y 1994.

An exhaustive search for the clinical records of patients diagnosed with tuberculous disease was done in the hospitals of the area under study, which involves 392,000 population. During the years 1992, 1993 and 1994. There were included: 1) patients who had positive bacilloscopy and/or positive Lowenstein's culture in any specimen: 2) patients younger than 35-years-old who had pleural effusion, significant Mantoux and adenosine deaminase (ADA) over 47 U/I in the pleural effusion. In total 814 patients remained in the study with an average age of 38.39(19.39 DE) in 1992, 39.02 (20.04 DE) in 1993, and 34.1 years-old (19.2 DE) in 1994, with extreme ages of 2 months and 87 years-old. The incidence/100,000 H was: in 1992: 67.86, in 1993: 66.58 and in 1994: 73.2. The contagious forms incidence/100,000 H was: 1.5 in 1992 and 1993; and 1.79 in 1994. The hospital mortality incidence/100,000 H was 2.04 in 1992, 2.30 in 1993 and 2.6 in 1994. We conclude that tuberculosis is endemic in our area with moderately high and stationary incidence.

[Hypertriglyceridemic pancreatitis and pregnancy]. / Pancreatitis hipertrigliceridémica y embarazo.

A 33-year-old secundipara with a history of gestational diabetes and familial hypertriglyceridemia exacerbated during her previous pregnancy was admitted in the 36th week of gestation with diffuse abdominal pain, vomiting, low-grade fever, and general malaise. A blood sample had a lipemic, milky-pink appearance and plasma concentrations were as follows: triglycerides 2173 mg/dL, cholesterol 320 mg/dL, amylase 801 U/L, lactate dehydrogenase 650 U/L, creatinine 1.5 mg/dL, glucose 380 mg/dL, and left-shifted white cells. Acute pancreatitis was diagnosed and owing to signs of fetal distress, a cesarean was performed under light general anesthesia with propofol, succinylcholine, and sevoflurane. After the umbilical cord was cut, rocoronium and fentanyl were administered. The neonate was healthy and the patient's condition evolved favorably with conservative treatment. The incidence of pancreatitis during pregnancy is low but related morbidity and mortality are high. The usual cause is biliary tract disease, although rare metabolic alterations such as hyperlipidemia may occasionally act as the trigger. Early diagnosis and treatment are the keys to successful surgery and postoperative recovery.

[Early extubation with caudal morphine after pediatric heart surgery]. / Extubación precoz con morfina caudal tras cirugía cardíaca pediátrica.

OBJECTIVES: To analyze the viability of immediate extubation of children after corrective surgery for congenital heart defects with extracorporeal membrane oxygenation using an anesthetic technique involving caudal morphine, and to study the effect on length of stay in the pediatric intensive care unit (PICU) or elsewhere in the hospital. MATERIAL AND METHODS: Twenty-nine ASA I-II patients without coagulation alterations undergoing surgery to correct simple heart defects were selected for extubation after surgery. Anesthesia was provided with with sevoflurane, midazolam, rocuronium, fentanil (maximum dose 10 micrograms/Kg) and a bolus of caudal morphine (50-60 micrograms/Kg) after anesthetic induction. Patient characteristics, type of surgery, times of extracorporeal circulation and of ischemia, arterial blood gases upon arrival in the PICU, postoperative complications and quality of analgesia were the variables analyzed. We also compared length of stay in the PICU and hospital for the study group and for a historical control group of 23 patients who had no received caudal morphine or been selected for early extubation. RESULTS: All patients were extubated satisfactorily in the operating room. None required reintubation or reoperation. Postoperative pain was controlled with metamizol alone for 79.3%. No episodes of respiratory depression or neurological complications were observed. PICU and hospital stays were significantly shorter in the study group than in the control group. CONCLUSIONS: Of patients undergoing simple corrective heart surgery with extracorporeal membrane oxygenation immediate extubation did not increase postoperative morbimortality and shortened the hospital stay. A single dose of caudal morphine provided optimum conditions for extubation and good control of postoperative pain. Strict measures must be taken, however, to avoid postpuncture bleeding.

Cross-sectional study of HPV-16 infection in a population-based subsample of Hispanic adults.

OBJECTIVE: This study aimed to estimate the prevalence and correlates of seropositivity to human papillomavirus (HPV)-16 in a subsample of adults who participated in the parent study Epidemiology of Hepatitis C in the adult population of Puerto Rico (PR). SETTING: The parent study was a population-based household survey aimed to estimate the seroprevalence of hepatitis C and other viral infections (hepatitis A, hepatitis B, HIV, and herpes simplex type 2) in PR (n=1654) between 2005 and 2008. PARTICIPANTS: A subsample of the last 450 consecutive adults aged 21-64 years, recruited between February 2007 and January 2008, who participated in the parent study and agreed to participate in HPV testing. PRIMARY AND SECONDARY OUTCOME MEASURES: The samples were tested by ELISA for HPV-16 viral-like particle-specific immunoglobulin G. Information on sociodemographic, health, and lifestyle characteristics was collected. Logistic regression modelling was used to estimate the prevalence odds ratio (POR) to assess factors associated to HPV-16 seropositivity. RESULTS: Prevalence of seropositivity to HPV-16 was 11.3%. Seroprevalence was higher in women (15.8%) than men (5.6%; p=0.001). After adjusting for age and sex, ever smokers (POR 2.06, 95% CI 1.08 to 3.92) and participants with at least five lifetime sexual partners (POR 2.91, 95% CI 1.24 to 6.81) were more likely to be HPV-16 seropositive. CONCLUSIONS: HPV-16 seropositivity is similar to that reported in the USA (10.4%) for NHANES 2003-2004 participants, although different assays were used in these studies. While future studies should evaluate HPV seroprevalence using a larger population-based sample, our results highlight the need to further understand the burden of HPV infection and HPV-related malignancies in PR, population with a low vaccine uptake.

[Autosomal recessive diseases with mental retardation]. / Enfermedades autosómicas recesivas con retraso mental.

INTRODUCTION: Autosomal recessive diseases with mental retardation are disorders that affect autosomes, and their genetic expression occurs in individuals who are homozygotic for a mutation, while heterozygotic subjects are unaffected carriers. If both parents are carriers, the theoretical possibility of their children also being carriers is 50%, the risk of the children being affected by the disease is 25%, and there is a 25% chance of their being healthy. They are an important source of mental deficiencies and inborn errors of metabolism (IEM) are some of their characteristic syndromes. DEVELOPMENT: The genetic disorders known as IEM can be classified according to the metabolism they affect, that is, purines, pyrimidines, amino acids, and so on. One of the lysosomal disorders is Tay-Sachs disease, which is rare among the general population but is very frequent in populations with a high rate of consanguinity, such as the Ashkenazi Jews. One of the most notable disorders affecting the metabolism of amino acids is the case of phenylketonuria due to mutations in the phenylalanine hydroxylase gene (PAH). It accounts for 0.5-1% of mental diseases and appears with a frequency rate of between 1/11,500 and 1/14,000 in newborn infants. Its early diagnosis through neonatal screening programmes makes it possible to start administering a phenylalanine-free diet and thus prevent mental retardation. CONCLUSIONS: Knowledge of this kind of autosomal diseases with neurological involvement, together with their correct and early diagnosis, makes it possible to establish suitable treatment regimens in some cases and to carry out genetic counselling in all of them.

[Experimental models used in research into genetic disorders that involve intellectual disability]. / Modelos experimentales utilizados en la investigación de trastornos genéticos que cursan con discapacidad intelectual.

INTRODUCTION: A basic principle of molecular and clinical medicine states that the function of the organs and the cells they are made up of is determined by the overall set of specific proteins. Therefore, the function of each organ depends on the molecules present in each cell, and hence it comes as no surprise to find that when tissue function is altered, different changes have taken place in the proteins. In the nervous system there are numerous examples of changes in proteins that correlate with functional alterations, either during normal or pathological development. DEVELOPMENT: In order to understand these relations, and to establish models in which to study the aetiopathogenesis of the disease, it is necessary to direct steady synthesis or to suppress synthesis in the brain of the protein that is potentially involved in the development of the disease. In consequence, it is possible to determine whether the presence or the absence of the protein is the direct or indirect cause of the effects; this is one of the main goals that must be achieved in order to enable researchers to define potential therapeutic targets in hereditary diseases. In order to manipulate the specific protein causing a pathology, we use experimental animal models as essential research tools, since they enable us to determine which mechanisms are altered and how the function of a particular protein affects the mechanisms being studied. CONCLUSIONS: Suppressing a gene or its over-expression in models using genetically modified mice will provide us with a means of modifying the genome and, eventually, the protein in the different tissues as well as in the nervous system in an attempt to imitate the genetic pathology that involves mental retardation. By controlling or suppressing the expression of a protein in the brain it becomes possible to remodel the functional profile of the tissue and study the consequences of molecular genetic manipulation, together with the biochemical, cytological and physiological processes, under normal basal conditions and under specific stimuli or conditions such as stress.

[Large-scale genotyping in research into autism spectrum disorders and attention deficit hyperactivity disorder]. / Genotipado a gran escala en la investigación del trastorno del espectro autista y el trastorno por deficit de atención con hiperactividad.

INTRODUCTION AND DEVELOPMENT: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are two neuropsychiatric disorders beginning in childhood that present a high degree of familial aggregation. ASD is characterised by social interaction and communication disorders, whereas patients with ADHD display persistent inattention and/or hyperactive-impulsive behaviour. With the exception of a few cases of autism in which cytogenetic anomalies or mutations have been reported in specific genes, the aetiology of these diseases remains unknown. This is a group of multifactorial diseases with several genes having a lesser effect and there is also an environmental component. Genetic linkage studies have pointed to about 20 chromosomal regions that could well contain genes that grant susceptibility to autism, to ADHD or to both disorders. The challenge to researchers lies in the clinical characterisation, recruitment of patients with ASD and ADHD, gene dosage quantification studies, comparative genomic methylation and hybridisation in order to identify chromosomal rearrangements in patients with autism and severe mental retardation. CONCLUSIONS: Genotyping large SNP-type collections that are potentially functional in genes that are candidates for these disorders, based on pharmacological, biochemical and neuropathological data together with that coming from animal models and linkage studies in a wide collection of samples from patients and controls, will enable us to identify the genetic components of these pathologies and to define their biological foundations.

Prevalence of sleep disordered breathing and sleep apnea in 50- to 70-year-old individuals. A survey.

PURPOSE: To determine the prevalence of sleep disordered breathing (SDB) and sleep apnea syndrome (SAS) in a general population aged from 50 to 70 years. SUBJECTS AND METHODS: We recruited 76 individuals aged between 50 and 70 years, chosen at random from the electoral census. They were invited to the clinic where a detailed medical history was taken and physical examination, ENT examination, pulmonary function tests and night time recording of respiratory variables performed. RESULTS: The prevalence of SDB (apnea-hypopnea index >/= 5) was 28.9%, and there were no differences between men (28%) and women (30%). However, the prevalence of SAS was 6.8%, and there were differences between men (5 cases) and women (0 cases) (p = 0.0521). Subjects in the SDB group had higher systolic blood pressure than in the non-SDB group (p < 0.05). CONCLUSIONS: SDB and SAS are common among 50- to 70-year olds. The prevalence of SDB was 28.9% and the prevalence of SAS was 6.8%.