Analysis of cognitive performance and polymorphisms of SORL1, PVRL2, CR1, TOMM40, APOE, PICALM, GWAS_14q, CLU, and BIN1 in patients with mild cognitive impairment and cognitively healthy controls.

INTRODUCTION: Alzheimer disease risk polymorphisms have been studied in patients with dementia, but have not yet been explored in mild cognitive impairment (MCI) in our population; nor have they been addressed in relation to cognitive variables, which can be predictive biomarkers of disease. OBJECTIVE: To evaluate cognitive performance and presence of polymorphisms of the genes SORL1(rs11218304), PVRL2(rs6859), CR1(rs6656401), TOMM40(rs2075650), APOE (isoforms ε2, ε3, ε4), PICALM(rs3851179), GWAS_14q(rs11622883), BIN1(rs744373), and CLU(rs227959 and rs11136000) in patients with MCI and healthy individuals. METHODOLOGY: We performed a cross-sectional, exploratory, descriptive study of a prospective cohort of participants selected by non-probabilistic sampling, evaluated with neurological, neuropsychological, and genetic testing, and classified as cognitively healthy individuals and patients with MCI. Cognition was evaluated with the Neuronorma battery and analysed in relation to the polymorphic variants by means of measures of central tendency, confidence intervals, and nonparametric statistics. RESULTS: We found differences in performance in language and memory tasks between carriers and non-carriers of BIN1, CLU, and CR1 variants and a trend towards poor cognitive performance for PICALM, GWAS_14q, SORL1, and PVRL2 variants; the APOE and TOMM40 variants were not associated with poor cognitive performance. DISCUSSION: Differences in cognitive performance associated with these polymorphic variants may suggest that the mechanisms regulating these genes could have an effect on cognition in the absence of dementia; however, this study was exploratory and hypotheses based on these results must be explored in larger samples.

Analysis of cognitive performance and polymorphisms of SORL1, PVRL2, CR1, TOMM40, APOE, PICALM, GWAS_14q, CLU, and BIN1 in patients with mild cognitive impairment and cognitively healthy controls. / Análisis de desempeños cognitivos y polimorfismos en SORL, PVRL2, CR1, TOMM40, APOE, PICALM, GWAS_14q, CLU y BIN1 en pacientes con trastorno neurocognitivo leve y en sujetos cognitivamente sanos.

INTRODUCTION: Alzheimer disease risk polymorphisms have been studied in patients with dementia, but have not yet been explored in mild cognitive impairment (MCI) in our population; nor have they been addressed in relation to cognitive variables, which can be predictive biomarkers of disease. OBJECTIVE: To evaluate cognitive performance and presence of polymorphisms of the genes SORL1(rs11218304), PVRL2(rs6859), CR1(rs6656401), TOMM40(rs2075650), APOE (isoforms ɛ2, ɛ3, ɛ4), PICALM(rs3851179), GWAS_14q(rs11622883), BIN1(rs744373), and CLU (rs227959 and rs11136000) in patients with MCI and healthy individuals. METHODOLOGY: We performed a cross-sectional, exploratory, descriptive study of a prospective cohort of participants selected by non-probabilistic sampling, evaluated with neurological, neuropsychological, and genetic testing, and classified as cognitively healthy individuals and patients with MCI. Cognition was evaluated with the Neuronorma battery and analysed in relation to the polymorphic variants by means of measures of central tendency, confidence intervals, and nonparametric statistics. RESULTS: We found differences in performance in language and memory tasks between carriers and non-carriers of BIN1, CLU, and CR1 variants and a trend toward poor cognitive performance for PICALM, GWAS_14q, SORL1, and PVRL2 variants; the APOE and TOMM40 variants were not associated with poor cognitive performance. DISCUSSION: Differences in cognitive performance associated with these polymorphic variants may suggest that the mechanisms regulating these genes could have an effect on cognition in the absence of dementia; however, this study was exploratory and hypotheses based on these results must be explored in larger samples.

[Interpretation of proverbs and Alzheimer's disease]. / Interpretación de refranes y enfermedad de Alzheimer.

AIM: To evaluate the performance of patients with Alzheimer's disease (AD) in the mild-moderate stage in a verbal material abstraction task that involves interpreting the implicit meaning of proverbs and sayings. SUBJECTS AND METHODS: A qualitative-quantitative analysis was carried out of the performance of 30 patients with AD and 30 controls, paired by age, gender and level of education. RESULTS: Patients had significantly greater difficulties than the controls when it came to interpreting proverbs. A high correlation was found between subjects' years of schooling and the overall score on the proverb interpretation test. Results suggest that the processes that may be predominantly affected in patients with AD are the investigation of the conditions of the problem, together with selecting an alternative and formulating a cognitive plan to resolve the task. CONCLUSIONS: The results help to further our knowledge of the characteristics of performance of patients with AD in a test involving the interpretation of the implicit meaning of proverbs and also provide information about the processes that may be predominantly affected. Further research is needed, however, on this subject area in order to obtain more conclusive explanations.

Aerosol orgotein (Ontosein) for the prevention of radiotherapy-induced adverse effects in head and neck cancer patients: a feasibility study.

Orgotein is an anti-inflammatory superoxide dismutase agent successfully used in treating several inflammatory diseases. It is also used in treating radiation-induced adverse effects in difference malignancies, notably breast, lung, bladder, prostate, cervix, and head and neck cancers. It is administered either topically or parenterally. To our knowledge, it has never been used before for prophylaxis of radiation-induced adverse effects or in aerosol form. Here we report on the results from a feasibility study on aerosol orgotein (Ontosein) for prevention of acute and deferred radiation-induced adverse effects in patients treated for head and neck malignancies. Our results show that aerosol orgotein administered before each radiation therapy session may impart some benefits in both incidence and severity of acute and deferred radiation-induced adverse effects in head and neck cancer patients, when compared with historical controls. In addition, aerosol orgotein administration is easy and convenient for both the patient and the radiotherapist.

[Present and future of kidney transplantation]. / Presente y futuro del trasplante renal.

Renal transplant is the treatment of choice for the patient with end stage renal disease. Spain is the country with the highest donation rate (33 ppm). However, at present this figure is stabilized. The development of non-beating heart programmes, living-donor nephrectomy (specially laparoscopic nephrectomy) programmes, and may be xenotransplantation in a non-immediate future could increase the transplantation activity. The knowledge of preservation mechanisms, specially with the use of perfusion machines allows to rescue for transplantation kidneys with a long warm-ischemia time. Furthermore, these machines are useful for analyzing viability markers. The new immunosuppressive drugs: Tacrolimus, Mycophenolate-Mophetil, Rapamycin and monoclonal antibodies against alpha chain of the interleukine-2 receptor (Basoliximab and Dazcizumab) have reduced the incidence of acute rejection in the immediate renal transplant period. However, its effect in the long-term follow-up period is still a matter of controversy. The incidence of tumour in the renal transplant recipient is increased, specially those of lymphoma, skin cancer and Kaposi sarcoma. Periodical exams for detecting the development of tumours are mandatory in this population. Finally, xenotransplantation is an attractive alternative, although immunological, infective and ethical barriers should previously be resolved.

Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia.

Nearly all mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid beta precursor protein (APP) genes lead to early-onset Alzheimer disease (EOAD, onset age at or before 65 years). In order to assess the genetic contribution of these genes in a series of Colombian AD cases, we performed a systematic mutation analysis in 11 autosomal dominant, 23 familial, and 42 sporadic AD patients (34% with age of onset < or = 65 years). No APP missense mutations were identified. In three autosomal dominant cases (27.2%), two different PSEN1 missense mutations were identified. Both PSEN1 mutations are missense mutations that occurred in early-onset autosomal AD cases: an I143T mutation in one case (onset age 30 years) and an E280A mutation in two other cases (onset ages 35 and 42 years). In addition, a novel PSEN1 V94M mutation was present in one early-onset AD case without known family history (onset age 53 years) and absent in 53 controls. The E318G polymorphism was present in five AD cases and absent in controls. In PSEN2, two different silent mutations were detected, including one not reported elsewhere (P129). The majority of the Colombian AD cases, predominantly late-onset, were negative for PSEN and APP mutations.

APOE epsilon4 and Alzheimer's disease: positive association in a Colombian clinical series and review of the Latin-American studies.

OBJECTIVE: As the strength of the association between the APOE epsilon4 allele and Alzheimer's disease (AD) varies across ethnic groups, we studied if there was such an association in Colombian patients. METHOD: We performed apolipoprotein E (APOE) genotyping in a clinical sample of 83 unrelated AD patients, predominantly late-onset (>65 yrs) including familial ( n =30) and sporadic AD cases (n= 53) diagnosed according to NINCDS-ADRDA criteria and assessed by a multi-disciplinary team. Control subjects (n = 44) had no significant cognitive impairment by medical interview and neuro-psychological testing. RESULTS: We found a high association (OR= 5.1 95%CI 1.9 -13.6) between APOE epsilon4 and AD, in this series with predominantly late-onset cases with familial aggregation in 24 cases (28.9%). A significant negative association was found between epsilon2 and AD (OR= 0.2 95% CI 0.05-0.75). CONCLUSION: Further population-based surveys in Colombia are warranted to precise a possible dose effect of APOE epsilon4.

Deterioro selectivo del lenguaje debido a degeneracion temporo focal: analisis comparativo entre un caso de afasia primaria progresiva y un caso de demencia semantica / Selective deterioration of languaje by temporal lobe athrophy

La doble disociación entre el sistema semántico y el fonológico se evidencia en la presentación de dos casos con degeneración focal bilateral de los lóbulos temporales. Uno, con pérdida progresiva y selectiva de los aspectos fonológicos, con una profunda agnosia auditiva verbal y no-verbal y parafasias fonológicas en la denominación, con conservación de la semántica; el otro, con una pérdida progresiva pero selectiva de los aspectos semánticos del lenguaje, con conservación del nivel fonológico, evidente en la excelente discriminación de los sonidos del lenguaje, buena repetición y escritura fonológica, pero ausencia de comprensión de los significados de las palabras, caras o figuras, y producción exclusiva de parafasias semánticas en pruebas de denominación.El primer caso (AV), es de un paciente evaluado a los 52 años, con un deterioro progresivo de 10 años de evolución, caracterizado por pérdida de la capacidad para comprender el lenguaje, percibiéndolo como un lenguaje extranjero. Este paciente presenta dificultades de identificación fonológica, de discriminación de sonidos, de repetición y desintegración fonológica en la denominación y en la escritura. El segundo caso (OV), es de una mujer de 60 años, evaluada por un deterioro progresivo de las capacidades de denominación, de 7 años de evolución. El perfil global es el de una paciente que, en su lenguaje, conserva los niveles fonológicos y sintácticos, pero tiene un compromiso significativo de la memoria semántica. En ambos pacientes, el examen neurológico es normal, excepto por los hallazgos en la esfera mental; no tienen antecedentes patológicos familiares y hay ausencia de enfermedad cardiovascular. Ambos presentan depresión, reactiva a la conciencia del deterioro. La paciente con alteración de la semántica conserva intactas sus habilidades atencionales, práxicas y de pensamiento; en el TAC cerebral se evidencia atrofia temporal bilateral de predominio izquierdo. Contrariamente, con la evolución de la enfermedad, el paciente con alteración de la fonología, ha venido presentando un déficit cognoscitivo global; el TAC cerebral se observa atrofia bitemporal de predominio derecho. Con la presentación de estos dos casos, se presenta evidencia de la fragmentación de los niveles semánticos y fonológicos del lenguaje y se realiza una diferenciación clínica entre afasia primaria progresiva, demencia semántica, enfermedad de Pick y enfermedad de Alzheimer

Classification deficits in Alzheimer's disease with special reference to living and nonliving things.

The present study was conducted to assess the hypothesis that visual similarity between exemplars within a semantic category may affect differentially the recognition process of living and nonliving things, according to task demands, in patients with semantic memory disorders. Thirty-nine Alzheimer's patients and 39 normal elderly subjects were presented with a task in which they had to classify pictures and words, depicting either living or nonliving things, at two levels of classification: subordinate (e.g., mammals versus birds or tools versus vehicles) and attribute (e.g., wild versus domestic animals or fast versus slow vehicles). Contrary to previous results (Montañes, Goldblum, & Boller, 1995) in a naming task, but as expected, living things were better classified than nonliving ones by both controls and patients. As expected, classifications at the subordinate level also gave rise to better performance than classifications at the attribute level. Although (and somewhat unexpectedly) no advantage of picture over word classification emerged, some effects consistent with the hypothesis that visual similarity affects picture classification emerged, in particular within a subgroup of patients with predominant verbal deficits and the most severe semantic memory disorders. This subgroup obtained a better score on classification of pictures than of words depicting living items (that share many visual features) when classification is at the subordinate level (for which visual similarity is a reliable clue to classification), but met with major difficulties when classifying those pictures at the attribute level (for which shared visual features are not reliable clues to classification). These results emphasize the fact that some "normal" effects specific to items in living and nonliving categories have to be considered among the factors causing selective category-specific deficits in patients, as well as their relevance in achieving tasks which require either differentiation between competing exemplars in the same semantic category (naming) or detection of resemblance between those exemplars (categorization).

The naming impairment of living and nonliving items in Alzheimer's disease.

Several studies of semantic abilities in Dementia of the Alzheimer Type (DAT) suggest that their semantic disorders may affect specific categories of knowledge. In particular, the existence of a category-specific semantic impairment affecting, selectively, living things has frequently been reported in association with DAT. We report here results from two naming tasks of 25 DAT patients and two subgroups within this population. The first naming task used 48 black and white line drawings from Snodgrass and Vanderwart (1980) which controlled the visual complexity of stimuli from living and nonliving categories. The second task used 44 colored pictures (to assess the influence of word frequency in living vs. nonliving categories). Within the set of black and white pictures, both DAT patients and controls obtained significantly lower scores on high visual complexity stimuli than on stimuli of low visual complexity. A clear effect of semantic category emerged for DAT patients and controls, with a lower performance on the living category. Within the colored set, pictures corresponding to high frequency words gave rise to significantly higher scores than pictures corresponding to low frequency words. No significant difference emerged between living versus nonliving categories, either in DAT patients or in controls. In the two tasks, the two subgroups of DAT patients presented a different profile of performance and error type. As color constitutes the main difference between the two sets of pictures, our results point to the relevance of this cue in the processing of semantic information, with visual complexity and frequency also being very relevant.

[Liver transplantation in pediatrics. Nutritional measures]. / Trasplante hepático en pediatría. Medidas nutricionales.

Malnutrition is a constant in candidates for liver transplant. Because of their particular characteristics, pre-operative nutritional intervention is difficult to apply, so that post-transplant action is necessary. A retrospective study was made, reviewing the clinical records of all the children undergoing liver transplants in 1992 in the "La Paz" Children's Hospital, while they were in the Pediatric Intensive Care Unit. Two groups of patients were established--A and B--respectively of 15 and 7 children, according to whether or not they had received immediate post-transplant TPN. In Group A, a total of 150 days was evaluated, with TPN (x = 10 +/- 8.3). The amino acid solutions used were for liver insufficiency (48.8%), Kidney insufficiency (33.3%) and standard (17.8%). Lipids were administered on 6.3% of days in four patients' nutrition. In 54.5% of interventions, infectious complications occurred due to immune-suppression. Comparison of the two patient groups show significant results: those in Group A had a 3.2 relative risk of suffering infection (certainty interval 1.3-1.8). In terms of time in the ICU, the Group A patients were admitted for an average of 13.4 days (range 2-37) as opposed to the 6.28 days of Group B (range 3-15). Results were significant, with p < 0.05. In terms of evolution, the survival rate in patients receiving TPN was 86.6% against 71.4% in those receiving enteral nutritional (n.s.). Our results show a high rate of survival (86.6%). It is not possible to conclude the extent to which the introduction of TPN influenced post-operative evolution, as there was no consistency in terms of the patients' clinical situation.

[Standard formulas of parenteral nutrition. A study of their use in a general hospital]. / Fórmulas estándar de nutrición parenteral. Estudio de su utilización en un hospital general.

The goal of the study was to evaluate the use of parenteral nutrition formulas with standardized g. of nitrogen, carbohydrates and lipids, and to analyze whether the nutritional requirements of the patients treated in our hospital were covered by said formulas or whether it was necessary to change and/or standardize a new formula. To do so, a review was made of 5.646 parental nutrition mixtures prepared in the Pharmacy Service and patterned by the Nutrition Service from April, 1991, to May, 1992, for 308 adult patients. The distribution of the mixtures by services, diagnoses and the frequency of the different standard formulas were studied, comparing standard formula frequency with that of non-standard formulas. Findings showed that 41.9% of nutrition mixtures were patterned in surgery, and the most common diagnosis, cancer, appeared in 24%. Of the mixtures, 67.6% were preestablished formulas, and 32.4% were non-standard formulas. The order of frequency among standard formulas was: basic standard formulas, stress formulas, initial formulas, peripheral formulas, hemodialysis formulas and low-volume formulas. All covered the nutritional needs of a large share of the patients for the different pathologies in which they were indicated. Nevertheless the question of designing a new formula to cover a greater number of situations was raised. Protocolization should take place rationally, to meet the hospital's most frequent pathologies, and effectiveness should be evaluated after tracking and checking each patient.

[Folates in human nutrition, Different clinical situations in which folate deficiencies exist]. / Folatos en nutrición humana. Diferentes situaciones clínicas en las que existe déficit de folatos.

The alimentary surveys carried out on various sectors of the population in industrialized countries have shown the existence of chronic clinically silent deficiency in micronutrients. In some cases, as in folates, their lability against conservation techniques, the change in alimentary habits, the abuse of alcohol and the great quantity of frequently used drugs which interfere in their absorption, diminish their content in the diet and their bio-availability. The appearance of macrocytic anemia is a late deficiency sign, and therefore in situations of an increase need and in patients included in the risk groups, a supplemental intake must be given in order to avoid irreversible lesions if it is not possible to monitor the folate levels. There are risk groups in which various etiological factors come into play, acting at a different metabolic level on the folates and making more difficult their dietetic or pharmacological compensation even if supply is considerably increased. We studied these factors independently and in each specific situation (old people, patients with liver disease, alcoholics, pregnant women and nursing mothers, neonates, children, malabsorption syndromes, gastrectomy, AIDS, anaesthesia and patients being treated with antifolic medication), evaluating their mechanisms of action and their potentiation in determined specific situations.

Phonological transformations in Spanish-speaking aphasics.

Thirty-seven aphasic patients whose native language is Spanish were divided into four groups: (1) Broca's, (2) Wernicke's, (3) Conduction, and (4) Anomia. Phonological errors produced on repetition and object-naming tasks were analyzed in terms of type of transformation and degree of similarity between target and errors in terms of shared distinctive features. Segmental transformations were of the following types: (1) pure substitution, (2) pure addition, (3) deletion, (4) reduplicative addition (doublet creation)--anticipatory (right to left) or preservative (left to right), (5) reduplicative substitution (doublet creation)--anticipatory or perseverative, and (6) mutual exchanges. Pure substitutions were the most prevalent, exchanges, the least. Some error types were found to differentiate significantly between aphasic populations. We suggest that different mechanisms may underlie the same error type for different aphasic populations.

Echoic memory and language perception.

The purpose of this study was to analyze asymmetry in echoic memory as a relevant factor in language perception. Two experimental procedures were used: the presentation of temporally segmented words in fragments of 40, 80, 120 and 240 msec, separated by intervals of 40, 80, 120 and 240 msec, similar to the procedures used by A. W. F. Huggins (1975, Perception & Psychophysics, 18, 149-157); the presentation of two tones of short duration, "high" and "low," followed by an interference tone equivalent to the mean frequency of the two tones, closely following the procedure used by D. W. Massaro (1975, in D.W. Massaro (Ed.), Understanding language, New York: Academic Press). A stereophonic tape recorder was used as follows: one channel was employed for the presentation of the words or tones while, through the other channel, the subject received a white noise equivalent in intensity. All subjects carried out the task twice (right ear, left ear) and the order of presentation was counterbalanced. Only the first task showed differences between ears. Implications of the results are analyzed.

Partial psychic seizures and brain organization.

This research was an attempt to determine the cerebral areas involved in focal epileptic seizures accompanied by psychic manifestations. Six types of partial seizures involving psychic symptomatology and phonatory seizures were included in the study. Sixty-one clinical records of focal epilepsy, which had been revealed by means of a CT-scan examination, were analyzed and a subsample of 25 patients with psychic symptoms was selected. The scans taken of the lesions were transferred to a six-level standard template built for this purpose. Subsequently, templates of patients with the same type of seizures were superimposed. The critical zones for the seven types of seizures studied are presented. A clear correlation was found between these results and our present knowledge of functional brain organization.

Factors that influence the outcome of primary pulmonary hypertension.

Factors predicting life expectancy in primary pulmonary hypertension have not been well defined. Thirty four cases of primary pulmonary hypertension that had been followed up until death or for at least five years were reviewed retrospectively. Patients were divided into three groups: 18 patients who died within five years of presentation to hospital; 12 who survived more than five years; and four who improved and who lived for more than five years. The age at onset was similar in the three groups and, like symptoms and sex, did not predict life expectancy. Right heart failure during the course of the disease was associated with a poor outcome. Radiographic evidence of cardiac enlargement and evidence of right heart strain on electrocardiogram at presentation was also predictive of survival for less than five years. Pulmonary arteriolar resistance was higher and cardiac output lower in those with the shortest survival times. There was no relation between pulmonary artery pressure and length of survival. Systemic resistance varied directly with pulmonary resistance and served to maintain systemic pressure. Presentation in or after pregnancy and patency of the foramen ovale were associated with longer survival. In four patients there was evidence of regression of the disease by cardiac catheterisation and lung histology. Primary pulmonary hypertension is a heterogeneous condition in which life expectancy varies widely.

Rheumatoid arthritis and pulmonary hypertension. A report of three cases.

Three women with well established rheumatoid arthritis (RA) who developed pulmonary hypertension during the course of their disease are reported. In one patient there was mild pulmonary fibrosis but this appeared unrelated to the severity of the pulmonary hypertension. Another patient had increased platelet stickiness which may have contributed to this complication, whereas in the third patient, no contributing factors were apparent. The pulmonary complications of RA and their relationship to the development of pulmonary hypertension are discussed.

The heart in scleroderma: noninvasive assessment.

Myocardial fibrosis is found at postmortem examination in up to 80% of patient with scleroderma, yet many such patients have an entirely normal cardiovascular examination. Isometric handgrip exercise is a useful abnormality. By this method 15 patients with scleroderma (American Heart Association criteria) were compared with 15 sex and age-matched normals. Results showed that scleroderma patients had a depressed heart rate response to handgrip (p less than 0.05) and abnormal systolic and diastolic time intervals. They showed a decreased shortening of the ratio pre-ejection period to ejection time (p less than 0.05) and a lengthening of the isovolumic relaxation time compared with the control group who steadily shortened this period (p less than 0.01). These findings indicate increased stiffness and impaired contractility of the left ventricle as would be caused by an underlying fibrotic process otherwise undetectable. Immunohistological studies give support to this concept. Staining with monospecific antibodies to collagens types I to V of cardiac muscle from patients who, in life, had no overt cardiac disease, showed an excess deposition of collagens type I, III, and IV. In conclusion isometric exercise may provide a noninvasive method of unmasking subclinical fibrosis of the left ventricle in scleroderma, and immunopathological studies support these findings.