Forty years of Tuberculous meningitis: The new face of an old enemy.

BACKGROUND: Tuberculous meningitis (TBM) occurs in 1-5% of cases of tuberculosis. Without early treatment, mortality and permanent disability rates are high. METHODS: A retrospective study performed at a tertiary hospital in Madrid (Spain) to describe clinical, diagnostic, and therapeutic aspects of TBM and analyze epidemiological trends over forty years, divided into two intervals (1979-1998 and 1999-2018). RESULTS: Overall, TBM was diagnosed in 65 patients (1.8% of new tuberculosis diagnoses), 48 in the first period and 17 in the second one. Median age at diagnosis increased from 38.5 to 77 years (p = 0.003). The proportion of non-HIV immunosuppressed patients increased (from 2.1% to 29.4%, p < 0.001), while the percentage of patients with a history of drug-abuse decreased (from 33.3% to 5.9%, p = 0.027). The median time between the onset of neurological symptoms and lumbar puncture increased from seven to 15 days (p = 0.040). The time between the onset of symptoms and the initiation of tuberculostatic treatment also increased from eleven to 18 days (p = 0.555). Results from image, biochemical, and microbiological tests showed no differences between both periods. A decreasing trend was observed in survival rates at 1-week (from 97.9% to 64.7%, p < 0.001), 1-month (from 91.7% to 58.8%, p = 0.002) and 1-year (from 85.4% to 47.1%, p = 0.002) after TBM diagnosis. CONCLUSIONS: The profile of patients diagnosed with TBM has changed from a young HIV-infected patient with a history of drug addiction to an elderly patient with non-HIV immunosuppression. Diagnosis and start of treatment both experienced a noticeable delay in the second period, which could help explain the increase in mortality observed across the two periods.

[Three keys to the appropriate choice of oral antibiotic treatment in the respiratory tract infections]. / Tres claves para seleccionar el antibiótico oral adecuado en las infecciones respiratorias.

Exacerbation of chronic obstructive pulmonary disease and community-acquired pneumonia are the most frequent infections of the lower respiratory tract in daily clinical practice. Antibiotic selection is a crucial component in its treatment and, in most cases, it is performed empirically. Scientific societies make therapeutic recommendations based on scientific evidence and / or expert recommendations that are of great help to clinicians. Beta-lactams, fluoroquinolones and macrolides are the most commonly used drugs for oral administration. From a practical point of view, there are three keys to the appropriate choice of oral antibiotic treatment, which are the effectiveness, safety and the ecological impact on the patient's microbiota, including the development of resistance, which will be assessed in depth in this review.

Direct antimicrobial susceptibility testing from the blood culture pellet obtained for MALDI-TOF identification of Enterobacterales and Pseudomonas aeruginosa.

To standardize the methodology for conducting direct antimicrobial susceptibility testing (AST) of Enterobacterales and Pseudomonas aeruginosa causing bacteremia from positive blood culture pellets. Two methods for processing positive blood cultures with Enterobacterales and P. aeruginosa were compared: a conventional method for identification and AST versus a direct method obtaining a pellet for both matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) identification and direct AST. A total of 157 (145 Enterobacterales, 12 P. aeruginosa) positive blood cultures were included. Microorganism identification showed 100% concordance between both methods at species and genus level. Definitive AST results were obtained 24 h earlier with the rapid method than the conventional one (p < 0.001). Of the 2814 MICs generated, there were discrepancies with respect to the conventional method in 47 (1.7%), 0.3% being very major (VME) and 1.3% major (ME) errors. Better results for AST were obtained when colony counts with the pellet were ≥ 105 cfu/ml. The essential agreement (EA) for antibiotics tested in Enterobacterales was at least 97%, except for ampicillin (95%). Regardless of colony count, the greatest discrepancies were observed for first/s-generation cephalosporins and aminoglycosides. In P. aeruginosa, EA was at least 92%, except for piperacillin-tazobactam (84%) and cefepime (76%). No VME occurred except for ceftazidime (8%). ME occurred in piperacillin/tazobactam (16%), ticarcillin, ceftazidime, tobramycin, amikacin, and colistin (8% each). Direct use of the blood culture pellet permits fast AST in bacteremia of Enterobacterales, enabling the clinicians to perform an early treatment adjustment. However, for Pseudomonas aeruginosa, the data needs expanding to improve the reliability of this technique.

Suicidal traits in Marilyn Monroe's Fragments: an LIWC analysis.

BACKGROUND: Linguistic inquiry and word count (LIWC), a computerized method for text analysis, is often used to examine suicide writings in order to characterize the quantitative linguistic features of suicidal texts. AIMS: To analyze texts compiled in Marilyn Monroe's Fragments using LIWC, in order to explore the use of different linguistic categories in her narrative over the years. METHOD: Selected texts were grouped into four periods of similar word count and processed with LIWC. Spearman's rank correlation was used to assess changes in language use across the documents over time. The Kruskal-Wallis test was applied to compare means between periods and for each of the 80 LIWC output scores. RESULTS: Significant differences (p < .05) were found in 11 categories, the most relevant being a progressive decrease in the use of negative emotion words, a reduction in the use of long words in the third period, and an increase in the proportion of personal pronouns used as Monroe approached the time of her death. CONCLUSIONS: The consistently elevated usage of first-person personal singular pronouns and the consistently diminished usage of first-person personal plural pronouns are in line with previous studies linking this pattern with a low level of social integration, which has been related to suicide according to different theories.

A short-form version of the Boston Naming Test for language screening in dementia in a bilingual rural community in Galicia (Spain).

BACKGROUND: Aphasia, one of the core symptoms of cortical dementia, is routinely evaluated using graded naming tests like the Boston Naming Test (BNT). However, the application of this 60-item test is time-consuming and shortened versions have been devised for screening. The hypothesis of this research is that a specifically designed shortened version of the BNT could replace the original 60-item BNT as part of a mini-battery for screening for dementia. The objective of this study was to design a short version of the BNT for a rural population in Galicia (Spain). METHODS: A clinic group of 102 patients including 43 with dementia was recruited along with 78 healthy volunteers. The clinic and control groups were scored on the Spanish version of the Mini-mental State Examination (MMSE) and BNT. In addition, the clinic group was tested with standard neuropsychological instruments and underwent brain investigations and routine neurological examination. BNT items with specificity and sensitivity above 0.5 were selected to compose a short battery of 11 pictures named BNTOu11. ANOVA and mean comparisons were made for MMSE and BNT versions. Receiver operating characteristics (ROC) curves and internal consistency were calculated. RESULTS: Areas under ROC curves (AUC) did not show statistically significant differences; therefore BNTOu11's AUC (0.814) was similar to the 60-item BNT versions (0.785 and 0.779), to the short versions from Argentina (0.772) and Andalusia (0.799) and to the Spanish MMSE (0.866). BNTOu11 had higher internal consistency than the other short versions. CONCLUSIONS: BNTOu11 is a useful and time-saving method as part of a battery for screening for dementia in a psychogeriatric outpatient unit.

Adaptation and validation of the semi-structured interview for Psychological Autopsy (SSIPA) in Spanish.

OBJECTIVES: The aim of this work was to adapt and validate into Spanish the Semi-Structured Interview for Psychological Autopsy (SSIPA). METHOD: The SSIPA consists of 69 items distributed into four modules: precipitants and/or stressors, motivation, lethality, and intentionality. The original instrument was translated from Portuguese into Spanish and backtranslated by bilinguals persons. The resulting questionnaire was compared with the original and discussed by an expert panel. The adapted instrument was then applied to the relatives of 26 presumed suicide cases in Ourense (Spain) who voluntarily accepted to participate. Interviews were digitally recorded and evaluated using a decision-making algorithm by the interviewer and two independent judges blind to the results of the others. RESULTS: Interrater agreement was measured using Kappa statistics. Participation in the study (27.6%) was similar to that obtained in the original study in Brazil >(20%). The Kappa values obtained were statistically significant. Correlation index was considered good (k>0.60) or very good (k> 0.80) in 15 steps including 3 out of 4 final steps of each module and the final result of the autopsy; moderate (k> 0.40) in 8 steps, 3 of them located in the motivation's module; and weak (k> 0.20) just in 2 steps. CONCLUSIONS: The Spanish version of the SSIPA is a reliable instrument for psychological autopsy studies. Low correlation in two of the algorithm steps for decision making may be due to the lack of accuracy of the questionnaire and should be improved.

Paradoxical recovery in a bilingual patient with aphasia after right capsuloputaminal infarction.

We report the case of a bilingual dextral patient, who presented with an uncommon pattern of aphasic deficit following a right capsulo-putaminal infarction. In this patient, the linguistic deficit concerned the use of her mother tongue (Galician, L1) much more than the lesser practised second language (Spanish, L2). Our patient presented spontaneous fluent speech in L2 but not in L1, automatic translation into L2, and impaired repetition in L1, whereas comprehension was spared in both L1 and L2. Reading and writing were less valuable due to educational interference (reduced schooling). Spontaneous speech 16 months after the stroke showed the stability of the impairment. This is the first reporting of a crossed subcortical aphasia in a bilingual patient.

[Impaired facial emotion recognition in a case of right frontotemporal dementia]. / Alteración en el reconocimiento de emociones faciales en un caso de demencia frontotemporal de predominio derecho.

INTRODUCTION: After the description of its involvement in amydalin lesions, there has been growing interest in the last decade on the neuropsychological examination of impaired emotional recognition in different diseases. This study aims to demonstrate the existence of emotional recognition impairment in a case of frontotemporal dementia affecting right temporal lobe structures with an experimental battery. CLINICAL CASE: The case of 7 year long frontotemporal dementia with right temporal predominance, clinically characterized by behavior disorders such as loss of hygiene habits, eating food in bad condition, approach to marginal groups and other psychiatric disorders (megalomanic delusional ideation) is presented. The psychiatric, neurological, neuropsychological and neuroimaging examination are described. METHODS: Facial recognition impairments were assessed with a modification of Ekman and Friesen Task (1976). The results were compared with those obtained in three controls matched by age, and educational level. RESULTS: The case we report showed marked impairment in discrimination, matching, selection and naming of negative facial emotions (anger, fear, sadness and disgust). The impairment was more striking in the selection and naming paradigms. Anger was the most affected emotion. It was hypothesized if the impairment of emotional recognition could be in the base of certain behavior disturbances of the patient such as approach to marginal groups.

Validation of the Spanish version of the Addenbrooke's Cognitive Examination in a rural community in Spain.

BACKGROUND: The Addenbrooke's Cognitive Examination (ACE) is a brief cognitive test battery designed to detect and differentiate Alzheimer's disease (AD) and frontotemporal dementia (FTD). Translations of this instrument into French and Malayalam have been recently published OBJECTIVE: To adapt and validate the ACE into Spanish in a rural population of low-educational level. SUBJECTS: A clinical group, composed of 70 patients affected by dementia and 25 patients with memory complaints without dementia, was compared with 72 controls matched for gender, age and educational level METHOD: The clinical group was studied with standard neuropsychological instruments, all patients underwent neuroimaging [Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI), and Single Photon Emission Tomography (SPECT) in all cases of suspected FTD], as well as routine neurological examination. Both groups were studied with the ACE and Clinical Dementia Rating scale (CDR). Sensitivity, specificity, area under curve, reliability and Verbal-Language/ Orientation-Memory (VLOM) ratio were calculated. Subsequently, the sample was stratified regarding educational level in two groups. Receiver Operating Characteristics (ROC) curves were calculated for these conditions. Different cut-off points were calculated addressing educational level. RESULTS: ROC curves demonstrated the superiority of the ACE in the sub sample of patients that finished school at over 14 years old. VLOM ratio confirmed its usefulness for differential diagnosis between AD and FTD CONCLUSIONS: The Spanish version of the ACE is a useful instrument for dementia diagnosis. In our sample VLOM ratio results were useful for differential diagnosis between AD and FTD. Different cut-off points must be used for different educational levels.

[Validity of the Spanish version of the Addenbrooke's Cognitive Examination for the diagnosis of dementia and to differentiate Alzheimer's disease and frontotemporal dementia]. / El Addenbrooke's Cognitive Examination en español para el diagnóstico de demencia y para la diferenciación entre enfermedad de Alzheimer y demencia frontotemporal.

INTRODUCTION: The Addenbrooke's Cognitive Examination (ACE) is a brief bedside test battery to detect mild dementia and differentiate frontotemporal dementia (FTD) from Alzheimer's disease (AD). AIM: To validate the ACE in Spanish. PATIENTS AND METHODS: The study evaluated the Spanish version of ACE on 128 subjects consisting in two groups a patient group (n = 76) and a control subjects group (n = 52). The patient group was divided in AD (n = 54) based on the NINCDS-ADRDA criteria and FTD (n = 22) based on the Lund y Manchester criteria. All patients underwent clinical, neuropsychological, radiologic (MRI, CT, and SPECT), and laboratory evaluations. Group's differences were evaluated using ANOVA. The internal consistency of the Spanish version of the ACE was measured using the Cronbach's alpha coefficient. The discriminative capability of the Spanish version of the ACE was examined by the receiver operating characteristic (ROC) analysis. RESULTS: The cut-off score of 86 showed a sensitivity of 92% (CI 95% = 83.6-97.0) and a specificity of 96.2% (CI 95% = 86.8-99.4). The ROC curve showed higher sensitivity and specificity of the ACE than the Mini-Mental State Examination in discriminating the dementia and control group. The VLOM ratio (verbal fluency + language)/(orientation + memory) of < 1.82 discriminated for FTD and > 4.87 discriminated for AD. CONCLUSION: The Spanish version of ACE is a brief and reliable instrument for early detection of dementia in highly educated people and offers a simple objective index to differentiate AD and FTD. More studies in less educated people are warranted.

Conscious compensations for thought insertion.

Thought insertion and other experiences of alien control have been explained as a source monitoring deficit, that results from a disconnection between a cognitive system for willed actions and a different system that monitors them. The case we present is a schizophrenic patient that in order to consciously avoid feeling his thoughts as not belonging to himself performs them as a motor act of speech. We suggest an interpretation for this conscious compensation following C. Frith's neuropsychological model of schizophrenia.

Angiotensin AT(1) receptor phosphorylation and desensitization in a hepatic cell line. Roles of protein kinase c and phosphoinositide 3-kinase.

Desensitization and phosphorylation of the endogenous angiotensin II AT(1) receptor were studied in clone 9 liver cells. Agonist activation of AT(1) receptors blunted the response to subsequent addition of angiotensin II. Partial inhibition of the angiotensin II-induced calcium response was observed when cells were pretreated with dibutyryl cyclic AMP, tetradecanoyl phorbol acetate (TPA), vasopressin, or lysophosphatidic acid. All of these desensitization processes were associated with receptor phosphorylation. Angiotensin II-induced AT(1) receptor phosphorylation was partially blocked by the protein kinase C inhibitor bisindolylmaleimide I and by phosphoinositide 3-kinase inhibitors (wortmannin and LY294002); the actions of these inhibitors were not additive. Pertussis toxin pretreatment of cells also partially inhibited angiotensin II-induced AT(1) receptor phosphorylation. TPA-induced AT(1) receptor phosphorylation was completely blocked by bisindolylmaleimide I. AT(1) receptor phosphorylation was also induced by vasopressin and lysophosphatidic acid, and these effects were partially inhibited by bisindolylmaleimide I. Angiotensin II increased Akt/PKB (protein kinase B) phosphorylation and protein kinase C membrane association. The effect on Akt/PKB phosphorylation was blocked by phosphoinositide 3-kinase inhibitors. These findings indicate that clone 9 cells exhibit both homologous and heterologous desensitization in association with AT(1) receptor phosphorylation. In these hepatic cells, angiotensin II-induced receptor phosphorylation involves pertussis toxin-sensitive and -insensitive G proteins, and is mediated in part through protein kinase C and phosphoinositide 3-kinase.

Angiotensin AT1 receptors in Clone 9 rat liver cells: Ca2+ signaling and c-fos expression.

In C9 (Clone 9) liver cells, angiotensin 11 increased the intracellular Ca2+ content, inositol phosphate production and c-fos mRNA expression. Other angiotensins were also active with the order of potency being angiotensin II = angiotensin III >> angiotensin I > angiotensin IV. Losartan, but not PD 123177 (1-(4-amino-3-methyl)-5-diphenylacetyl-4,5,6,7-tetrahydro-1H-imida zo [4,5c]pyridine-6-carboxylic acid), blocked the effects of angiotensin II. Pertussis toxin did not alter these actions of angiotensin II. These data indicate that the effects were mediated through angiotensin AT1 receptors involving pertussis toxin-insensitive G-proteins. Phorbol myristate acetate was also able to increase c-fos mRNA expression. The action of angiotensin II was consistently greater than that of the active phorbol ester. Staurosporine but not genistein inhibited this effect of angiotensin II. Angiotensin II- and phorbol myristate acetate-induced proto-oncogene mRNA expression was attenuated in cells incubated overnight with the active phorbol ester, which suggests a major role of protein kinase C.

Cellular and subcellular distribution of 7B2 in porcine Merkel cells.

BACKGROUND: Merkel cells are neuroendocrine cells located in the skin and oral mucosa of various mammalian species. These cells express multiple peptides as well as serotonin. Although the precise function of Merkel cells is still unknown, different studies support its role as mechano-electric transducer. 7B2 granin (secretogranin V) is a polypeptide isolated from the pituitary gland and present in the dense-cored granules of neuronal and paraneuronal cells. METHODS: The expression of the 7B2 in Merkel cells of pig snout skin was analysed by immunohistochemical techniques. The streptavidin-biotin peroxidase complex procedure was employed for light microscopy. A postembedding method using immunoglobulin-colloidal gold complexes was employed for the ultrastructural studies. RESULTS: Immunoreactivity for 7B2 was observed in virtually all Merkel cells, both in epidermis and vibrissae. The immunostaining was shown in the basal side of cytoplasms where neuroendocrine granules were accumulated. Immunoelectron microscopy allowed us to demonstrate that 7B2 labelling was located on the electrondense granules. Nuclei and epidermal nerve terminals associated with merkel cells did not show immunoreactivity. CONCLUSIONS: The polypeptide 7B2 is present in the dense-cored granules of Merkel cells. This result is consistent with the possible role for 7B2 in secretory granules' processing. To our knowledge this is the first evidence of 7B2 protein in Merkel cells.

Characterization of the alpha 1-adrenoceptors of cat liver. Predominance of the alpha 1A-adrenergic subtype.

The alpha 1-adrenoceptors present in the liver of cats were characterized using [3H]prazosin. This radioligand binds to cat liver membranes with high affinity ((KD 0.79 nM) to a moderately abundant number of sites (160 fmol/mg of protein). This sites were characterized pharmacologically, by binding competition, observing the following orders of potency: a) for agonists: oxymetazoline > epinephrine = norepinephrine >> methoxamine, and b) for antagonists: WB4101 > or = prazosin > or = (+) niguldipine > or = benoxathian > or = spiperone = 5-methyl-urapidil > phentolamine > BMY 7378. These data suggested that cat liver expresses alpha 1A-adrenoceptors. Expression of the mRNA for this receptor was confirmed by RT-PCR.