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Mutational mechanism for DAB1 (ATTTC)n insertion in SCA37: ATTTT repeat lengthening and nucleotide substitution
No full textDynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently established that this neurodegenerative disease is caused by an (ATTTC)n insertion within an (ATTTT)n in a noncoding region of DAB1. We now investigated the mutational mechanism that originated the (ATTTC)n insertion within an ancestral (ATTTT)n . Approximately 3% of nonpathogenic (ATTTT)n alleles are interspersed by AT-rich motifs, contrarily to mutant alleles that are composed of pure (ATTTT)n and (ATTTC)n stretches. Haplotype studies in unaffected chromosomes suggested that the primary mutational mechanism, leading to the (ATTTC)n insertion, was likely one or more T>C substitutions in an (ATTTT)n pure allele of approximately 200 repeats. Then, the (ATTTC)n expanded in size, originating a deleterious allele in DAB1 that leads to SCA37. This is likely the mutational mechanism in three similar (TTTCA)n insertions responsible for familial myoclonic epilepsy. Because (ATTTT)n tracts are frequent in the human genome, many loci could be at risk for this mutational process.info:eu-repo/semantics/publishedVersio
Olanzapine-Induced Hyperprolactinemia: Two Case Reports
Get PDFBackground: Hyperprolactinemia is a common consequence of treatment with antipsychotics. It is usually defined by a sustained prolactin level above the laboratory upper level of normal in conditions other than that where physiologic hyperprolactinemia is expected. Normal prolactin levels vary significantly among different laboratories and studies. Several studies indicate that olanzapine does not significantly affect serum prolactin levels in the long term, although this statement has been challenged. Aims: Our aim is to report two olanzapine-induced hyperprolactinemia cases observed in psychiatric consultations. Methods: Medical records of the patients who developed this clinical situation observed in psychiatric consultations in the Psychiatry Department of the Prof. Dr. Fernando Fonseca Hospital during the year of 2017 were analyzed, complemented with a non-systematic review of the literature. Results: The case reports consider two women who developed prolactin-related symptoms after the initiation of olanzapine. No baseline prolactinemia was obtained, and prolactin serum levels were only evaluated after prolactin-related symptoms developed: at the time of its measurement, both patients had been taking olanzapine for more than 24 weeks. Hyperprolactinemia was found to be present in Case 2, whereas Case 1 (a 49-year-old woman) had "normal" serum prolactin levels for premenopausal and prolactin levels slightly above the maximum levels for postmenopausal women. Both patients underwent similar pharmacological adjustments, which comprised switches from olanzapine to aripiprazole. After all pharmacological changes, prolactin serum levels decreased to normal range values and prolactin-related symptoms disappeared. Discussion/Conclusions: Laboratorial and literature prolactinemia values variability and discrepancies may make the management of borderline hyperprolactinemia clinical situations difficult. Baseline prolactin levels should have been obtained, as they help in the management of patients who develop neuroleptic-induced hyperprolactinemia. Prolactin-related symptoms can occur with borderline or normal standardized prolactinemia values. Olanzapine-induced hyperprolactinemia is a rare but possible event. Aripiprazole was used as a suitable alternative for olanzapine-induced hyperprolactinemia.info:eu-repo/semantics/publishedVersio
Posterior Reversible Encephalopathy Syndrome and Azathioprine
Get PDFPosterior reversible encephalopathy syndrome (PRES) is a rare syndrome that presents with neurological manifestations, often associated with arterial hypertension. Magnetic resonance imaging (MRI) shows bilateral white matter oedema in the posterior vascular territories. Immunosuppression, (pre) eclampsia and autoimmune diseases can be implicated. A 27-year-old woman, with mixed connective tissue disease under azathioprine, was admitted in the emergency room in status epilepticus and with severe hypertension. The MRI showed bilateral oedema in a pattern compatible with PRES. There was clinical improvement after azathioprine suspension. PRES is typically reversible with prompt recognition of the syndrome and its trigger. The association with azathioprine is rare.
LEARNING POINTS:
Posterior reversible encephalopathy syndrome should be considered in patients with sudden onset of headache, altered consciousness and seizures.Recognition of this entity and identification of the trigger are essential for reversal of the clinical picture.Autoimmune diseases and some immunosuppressive drugs have been identified as causative, but reports of an association with azathioprine are very rare.info:eu-repo/semantics/publishedVersio
Derivation and external validation of the SHIeLD score for predicting outcome in normotensive pulmonary embolism
No full textIdentifying patients with normotensive pulmonary embolism (PE) who may benefit from thrombolysis remains challenging. We sought to develop and validate a score to predict 30-days PE-related mortality and/or rescue thrombolysis.
METHODS:
We retrospectively assessed 554 patients with normotensive PE. Independent predictors of the studied endpoint were identified from variables available at admission in the emergency department and were used to create a score. The model was validated in 308 patients from a separate hospital.
RESULTS:
A total of 64 patients died or needed rescue thrombolysis (44 in the derivation cohort). Four independent prognostic factors were identified: Shock index ≥ 1.0 (OR 3.33; 95% CI 1.40-7.93; P = 0.006), HypoxaemIa by the PaO2/FiO2 ratio (OR 0.92 per 10 units; 95% CI 0.88-0.97; P < 0.001), Lactate (OR 1.38 per mmol/L; 95% CI 1.09-1.75; P = 0.008) and cardiovascular Dysfunction (OR 5.67; 95% CI 2.60-12.33; P < 0.001) - SHIeLD score. In the development cohort, event rates for each risk tercile were 0.0%, 2.2%, and 21.6%. In the validation cohort, corresponding rates were 0.0%, 1.9%, and 14.3%. The C-statistic was 0.90 (95% CI 0.86-0.94, P < 0.001) in the derivation cohort and 0.82 (95% CI 0.75-0.89, P < 0.001) in the validation cohort. Decision curve analysis showed that the SHIeLD score is able to accurately identify more true positive cases than the European Society of Cardiology decision criteria.
CONCLUSIONS:
A risk score to predict 30-days PE-related mortality and/or rescue thrombolysis in patients with normotensive PE was developed and validated. This score may assist physicians in selecting patients for closer monitoring or aggressive treatment strategy.info:eu-repo/semantics/publishedVersio
Direct Gaze Partially Overcomes Hemispatial Neglect and Captures Spatial Attention
Get PDFDirect gaze has been shown to be a particularly important social cue, being preferentially processed even when unconsciously perceived. Results from several visual search tasks further suggest that direct gaze modulates attention, showing a faster orientation to faces perceived as looking toward us. The present study aimed to analyze putative modulation of spatial attention by eye gaze direction in patients with unilateral neglect. Eight right hemisphere stroke patients with neglect performed a target cancelation paradigm. Patients were instructed to cross all open-eyed pictures amidst closed eyed distractors. Target images were either in direct or averted gaze. Participants performed significantly better when observing targets with direct gaze supporting the hypothesis that this gaze direction captures attention. These findings further suggest that perception of direct gaze is able to diminish the visuospatial impairment seen in neglect patients.info:eu-repo/semantics/publishedVersio
Renal lithiasis from a nephrologist’s perspective
Get PDFMan has known urinary lithiasis since antiquity. In Portuguese medicine, this is a pathology seen predominantly from the urology perspective, but renal lithiasis is evaluated and treated preventively by nephrologists worldwide, and its study has contributed significantly to knowledge
of how the renal tubule works. Nephrolithiasis is a relatively common disease in the adult population and, in Portugal, is observed in about
7.3% of the population.
The main pathophysiological mechanisms of the most frequent types of kidney stones and who and how to conduct the metabolic research
are briefly described. Medical treatment is also addressed, keeping in mind that nephrolithiasis is often accompanied by extra-renal manifestations that should be investigated and treated, namely arterial hypertension, obesity, diabetes mellitus and osteo-metabolic disease.info:eu-repo/semantics/publishedVersio
Health-Related Quality of Life in Patients with Moderate to Severe Ulcerative Colitis: Surgical Intervention versus Immunomodulatory Therapy.
No full textPURPOSE:
Ulcerative colitis (UC) can be managed with immunomodulation or surgery. We aimed to understand whether these strategies had a different impact on patients' health-related quality of life (HRQoL).
METHODS:
This was a retrospective, cross-sectional study: patients who had a moderate to severe UC episode that prompted the utilization of immunomodulatory drugs or surgery were invited to complete a generic (short form [36] health survey [SF-36]) and a disease-specific (inflammatory bowel disease questionnaire [IBDQ]) survey.
RESULTS:
We included 157 patients, 65 (41.4%) surgically treated. The therapeutic procedure had a minimal impact on HRQoL: only the social dimension of the IBDQ and the physical function component of the SF-36 were significantly different between the study arms - lower for the surgically treated patients. The type of surgery had no impact, but the occurrence of pouchitis, namely, in a chronic form, was associated with a lower HRQoL. Regression analysis confirmed surgery as an independent predictor of lower scores in the social dimension of the IBDQ (-4.646, 95% CI -6.953 to -2.339) and in the physical functioning (-9.622, 95% CI -17.061 to -2.183) and physical role functioning (-3.669, 95% CI -7.339 to 0.001) dimensions of the SF36.
CONCLUSIONS:
Although usually feared by patients, surgery has a limited impact on UC patients HRQoL when compared to medical management with immunomodulatory drugs.info:eu-repo/semantics/publishedVersio