Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease

Using autoradiographic binding methodology with monoiodinated peptide YY together with the agonists neuropeptide Y (NPY) and NPY (13-36), as well as in situ hybridization with oligonucleotide probes complementary to the NPY Y2 receptor (Y2-R) mRNA, we have studied whether or not intracerebral prion inoculation affects Y2-Rs in male CD-1 mice. Monoiodinated peptide YY binding, mainly representing Y2-Rs, was down-regulated by 85% in the CA1 strata oriens and radiatum and by 50-65% in the CA3 stratum oriens 110-140 days postinoculation. In the CA3 stratum radiatum, where the mossy fibers from the dentate granule cells project, there was a significant decrease in PYY binding at 110-120 days. Y2-R mRNA, moderately expressed both in the CA1 and CA3 pyramidal cell layers and the granule cell layer in the dentate gyrus, showed a slight, but not significant, decrease in CA3 neurons 130 days postinoculation. The results indicate that the accumulation of the scrapie prion protein in the CA1-3 region strongly inhibits NPY binding at the Y2-Rs, which, however, is only marginally due to reduced Y2-R mRNA expression. The loss of the ability of NPY to bind to inhibitory Y2-Rs may cause dysfunction of hippocampal circuits and may contribute to the clinical symptoms in mouse scrapie.     

Non-invasive assessment of magnitude and dispersion of atrial cycle length during chronic atrial fibrillation in man

AIMS: Atrial fibrillation cycle lengths can be assessed from right precordial ECG leads and the unipolar oesophageal ECG using a non-invasive method called Frequency Analysis of Fibrillatory ECG. The purpose of this report is to present the results from application of this method in a large group of patients with long-term atrial fibrillation and to examine the differences between patients with 'coarse' and 'fine' atrial fibrillation. METHODS AND RESULTS: Simultaneous 15 min recordings from V1, V2 and an oesophageal lead at a position behind the posterior atrium were obtained in 28 patients, aged 41 to 78 years, with long-term (> 1 month) atrial fibrillation. In each lead, using the time averaging technique, the QRST complexes were suppressed. Thereafter, the frequency distribution of the residual ECG was estimated by means of Fast Fourier Transform. In the 3-12 Hz range of each lead, the dominant atrial cycle length, the power maximum and the spectral width were calculated. In 26 patients (93%), frequency spectra in the 3-12 Hz range could be obtained. The dominant atrial cycle length ranged from 120 to 175 ms, mean 150+/-16 (SD) ms in V1, and from 120 to 190 ms, mean 150+/-16 in an oesophageal lead (ns). The absolute difference in the dominant atrial cycle length between V1 and the oesophageal lead was 10.4+/-7.7 ms. There was no significant difference in the dominant atrial cycle length in V1 between patients with coarse and fine atrial fibrillation. The power maximum in V1 was significantly greater in patients with coarse compared to fine atrial fibrillation (P=0.01). The spectral widths ranged from 10 to 55 ms and demonstrated significantly higher mean values in lead V2 compared to V1 (P=0.001). Compared to V1, the mean values tended to be smaller in the oesophageal lead (P=0.05). CONCLUSIONS: Using the Frequency Analysis of Fibrillatory ECG method, the dominant atrial cycle length, power maximum and spectral width can be estimated from the frequency spectra in the majority of patients with atrial fibrillation. Spatial dispersion of the dominant atrial cycle length occurs in some patients and may be an important proarrhythmic marker. The distinction between coarse and fine atrial fibrillation cannot be used as a marker of the atrial cycle length.     

Antileishmanial chalcones: statistical design, synthesis, and three-dimensional quantitative structure-activity relationship analysis

A large number of substituted chalcones have been synthesized and tested for antileishmanial and lymphocyte-suppressing activities. A subset of the chalcones was designed by using statistical methods. 3D-QSAR analyses using 67 (antileishmanial activity) and 63 (lymphocyte-suppressing activity) of the compounds for the training sets and 9 compounds as an external validation set were performed by using the GRID/GOLPE methodology. The Smart Region Definition procedure with subsequent region selection as implemented in GOLPE reduced the number of variables to approximately 1300 yielding 3D-QSAR models of high quality (lymphocyte-suppressing model, R2 = 0. 90, Q2 = 0.80; antileishmanial model, R2 = 0.73, Q2 = 0.63). The coefficient plots indicate that steric interactions between the chalcones and the target are of major importance for the potencies of the compounds. A comparison of the coefficient plots for the antileishmanial effect and the lymphocyte-suppressing activity discloses significant differences which should make it possible to design chalcones having a high antileishmanial activity without suppressing the proliferation of lymphocytes.     

Caring for the older patient, Part II: Age-related anatomic and physiologic changes and pathologies

This is the second article of a four-part series on gerontology and its applications to the care of elderly patients in nuclear medicine. This article reviews anatomic and physiologic changes and pathology associated with aging. It also discusses tailoring nuclear medicine procedures according to patients' needs and conditions, as well as adopting changes within the nuclear medicine department to better serve older patients. Upon completion of this article, the reader should be able to: (a) describe normal age-related anatomic and physiologic changes that are observed in older patients; (b) identify common age-related disorders; (c) discuss considerations in tailoring nuclear medicine procedures for older patients; and (d) identify changes in the nuclear medicine facility that would better accommodate older patients.     

Introduction to the AFDC program. Aid to Families with Dependent Children

The NADYA Group, integrated in the Spanish Society of Parenteral and Enteral Nutrition (SENPE), and made up of professionals dedicated to Artificial Nutrition, and specifically, to Artificial Nutrition in the home, annually undertakes the task of collecting data on diagnosis, type of support, follow up characteristics, complications, and quality of life, of patients included in programs of at home artificial nutrition in Spain. In the Annual Register corresponding to 1994, 17 hospitality groups have participated, providing 369 patients with Home Enteral Nutrition, and 30 with Home Parenteral Nutrition. Home Enteral Nutrition is mainly applied in patients with neoplasias (36%) or neurological alterations (35%). The most commonly used access route in the nasogastric tube, although there is an observed increase in the application of Percutaneous Gastrostomies (21%) in relation to previous data of the Spanish population. There is an observed complications index of 0.07 episodes/patient-year, a mortality of 30% (neoplasias) and 20% (neurological alterations), and low rehabilitation indexes in this group. In Home Parenteral Nutrition, post-radiation enteritis, neoplasias, and mesenteric ischemia, are the main diagnostic groups. The majority of the patients have a tunneled tube (63%), with 37% using an implanted tube. With an index of hospitalizations of 0.83 hospitalizations/ patient-year, catheter septicemia justifies the majority of the re-hospitalizations derived from nutritional treatment (0.56 hospitalizations/patient-year), note the mortality of 37%. There are complete rehabilitations, continuing the previously normal activity in 80% of the cases.