Reasons prompting digitalis therapy in the acute care hospital.

Background: The choice of administering digitalis to older patients with congestive heart failure (CHF) cannot be made on the account of univocally defined criteria because of uncertainty about efficacy and concern about safety of digitalis in this population. The purpose of this study was to verify whether the clinical characteristics on admission to the acute care hospital determine the use of digitalis therapy in elderly patients.

Methods: A total of 1239 patients (mean age 77.

Trends in antihypertensive drugs in the elderly: the decline of thiazides.

The last decade has seen the publication of different editions of guidelines for the pharmacological treatment of hypertension that were based on the results of large, randomised trials. Since these guidelines were meant to inform practitioners, we analysed the pattern of prescription of antihypertensive agents between 1988 and 1997 among older hospitalised adults. Because of the wealth of data supporting the use of thiazides diuretics, we focused on diuretic prescription, to identify independent predictors of their utilisation.

Structural consequences of metal complexation of cyclo[Pro-Phe-Phe-Ala-Xaa]2 decapeptides.

The conformational features of both free and Ca2+-complexed cyclo[Pro-Phe-Phe-Ala-Xaa]2 (with Xaa= Glu(OtBu), Lys(CIZ), Leu, and Ala) in solution have been determined by NMR spectroscopy and extensive distance-geometry calculations. The decapeptides are conformationally homogeneous in solution and show common structural features in their free and complexed forms. The structures of the free form contain only trans peptide bonds and are topologically similar to the structure of gramicidin-S, folded up in two antiparallel extended structures, stabilized by interstrand hydrogen bonds, and closed at both ends by two beta-turns.

Immunocytochemical mapping of the phosphatase and tensin homolog (PTEN/MMAC1) tumor suppressor protein in human gliomas.

PTEN/MMAC1 (phosphatase and tensin homolog/mutated in multiple advanced cancers 1) is a tumor suppressor gene, the inactivation of which is an important step in the progression of gliomas to end-stage glioblastoma multiforme. We examined the distribution of PTEN protein in 49 primary human gliomas by immunocytochemistry using polyclonal antibodies that we raised against PTEN-glutathione S-transferase fusion proteins expressed in Escherichia coli. The study group consisted of 6 low-grade astrocytomas, 7 anaplastic astrocytomas, 21 glioblastomas multiforme, 4 low-grade oligodendrogliomas, 6 malignant oligodendrogliomas, and 5 malignant mixed oligoastrocytomas.

Predicting length of stay of older patients with exacerbated chronic obstructive pulmonary disease.

Our study objective was to identify factors predicting length of hospital stay of older patients with exacerbated chronic obstructive pulmonary disease (COPD) through a multicenter, cross-sectional, retrospective study. We examined 3789 patients aged 74.3+/-11.

Multicentric study of the effect of milk fermented by Lactobacillus casei on the incidence of diarrhoea.

The aim of this study was to determine if supplementation of healthy children with milk fermented by yogurt cultures and Lactobacillus casei strain DN-114 001 could affect the incidence of acute diarrhoea when compared with traditional yogurt. The study was a multicentre, randomised, double-blind trial, conducted over four months, on 928 children aged, at inclusion, 6-24 months. The study consisted of two periods: supplementation and observation.

Computational procedures to explain the different biological activity of DNA/DNA, DNA/PNA and PNA/PNA hybrid molecules mimicking NF-kappaB binding sites.

Peptide nucleic acids (PNA) have recently been proposed as alternative reagents in experiments aimed to the control of gene expression. In PNAs, the pseudopeptide backbone is composed of N-(2-aminoethyl)glycine units and therefore is stable in human serum and cellular extracts. PNAs hybridize with high affinity to complementary sequences of single-stranded RNA and DNA, forming Watson-Crick double helices and giving rise to highly stable (PNA)2-RNA triplexes with RNA targets.

Cognitive dysfunction as a major determinant of disability in patients with heart failure: results from a multicentre survey. On behalf of the GIFA (SIGG-ONLUS) Investigators.

Cognitive dysfunction is a frequent finding among older patients with left ventricular systolic dysfunction; however, the clinical outcomes of such a finding are unknown. Also, disability is a common condition in heart failure, poorly responding to commonly used cardiovascular medications. The association between cognitive dysfunction and disability was assessed in 1583 patients with heart failure, but without cerebrovascular disease, previous stroke, or Alzheimer's disease, who were enrolled during 2 years of a multicentre pharmacoepidemiology survey.

A snapshot of a transition state analogue of a novel thermophilic esterase belonging to the subfamily of mammalian hormone-sensitive lipase.

EST2 is a novel thermophilic carboxylesterase, isolated and cloned from Alicyclobacillus (formerly Bacillus) acidocaldarius, which optimally hydrolyses esters with acyl chain lengths of six to eight carbon atoms at 70 degrees C. On the basis of the amino acid sequence homology, it has been classified as a member of the mammalian hormone-sensitive lipase (HSL) subfamily. The crystal structure of EST2, complexed with a sulphonyl derivative, has been determined at 2.

Body mass index and mortality among hospitalized patients.

Background: Body mass index (weight in kilograms divided by the square of the height in meters [BMI]) is known to be associated with overall mortality. However, the effect of age on excess mortality from all causes associated with obesity is controversial. The aim of the present study is to determine the effect of age on the relationship between BMI and mortality.

Older age and in-hospital development of hypokalemia from loop diuretics: results from a multicenter survey. GIFA Investigators. Multicenter Italian Pharmacoepidemiologic Study Group.

Background: Hypokalemia is a common finding among older patients taking diuretic medications. However, it is not known whether older age per se carries an increased risk of hypokalemia, particularly during a patient's treatment with loop diuretics.

Methods: The association between age and incident hypokalemia was examined in 18,872 patients with normal baseline serum potassium enrolled during three yearly multicenter surveys; 4,035 patients started receiving loop diuretics during their hospital stay.

Use of calcium antagonists and hemoglobin loss in hospitalized elderly patients: a cohort study. Gruppo Italiano di Farmacoepidemiologia nell'Anziano (GIFA) investigators.

Objective: To assess the association between in-hospital use of calcium antagonists and incident reduction in hemoglobin levels, as well as the impact of individual baseline risk for gastrointestinal bleeding on such an association.

Methods: The association between calcium antagonists and hemoglobin decrease > 1.2 g/dL was examined in 6,721 patients enrolled in a collaborative pharmacoepidemiology study who did not take calcium antagonists before admission and with baseline hemoglobin > or =12 g/dL.

Solid state structural analysis of the cyclooctapeptide cyclo- (Pro1-Pro-Phe-Phe-Ac6c-Ile-D-Ala-Val8).

A solid state analysis of the cyclic octapeptide c(-Pro(1)-Pro-Phe-Phe-Ac(6)c-Ile-D-Ala-Val(8)-) (C8-CLA), containing the Pro-Pro-Phe-Phe sequence, followed by the bulky helicogenic C(alpha,alpha)-dialkylated 1-aminocyclohexane-1-carboxylic acid (Ac(6)c) residue and a D-Ala residue in position 7, has been carried out by x-ray diffraction. The crystals, grown from a DMSO solution, are monoclinic, space group P2(1) with a = 13.458(3) A, b = 19.

Antihypertensive drug therapy and hypoglycemia in elderly diabetic patients treated with insulin and/or sulfonylureas. Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA).

We performed this case control study to evaluate the risk of hypoglycemia associated with the use of antihypertensive drugs in older hospitalized diabetic patients treated with sulfonylureas and/or insulin. All diabetic patients admitted during 4 months in 1988, month in 1991, 4 months in 1993 and 4 months in 1995 (n = 3477, mean age 71.4 +/- 0.

The effect of supplementation with milk fermented by Lactobacillus casei (strain DN-114 001) on acute diarrhoea in children attending day care centres.

The objective of this study was to determine if supplementation with milk fermented by yogurt cultures and Lactobacillus casei (strain DN-114 001) could lessen acute diarrhoea in healthy children. The study was conducted over six months, with 287 children aged 18.9 (SD 6.

Use of antihypertensive drugs in the Italian hospitals. GIFA group. Gruppo Italiano di Farmacoepidemiologia nell'Anziano.

Calcium channel blockers and ACE-inhibitors are among the most common drugs prescribed for the initial treatment of hypertension. While their ability to control surrogate outcomes, such as blood pressure and left ventricular hypertrophy, is proven, there is limited evidence of their prevention of major cardiovascular events, including mortality. The aim of our work was to assess the use of these drugs in Italy in comparison with beta-blockers and diuretics.

Pharmacosurveillance in hospitalized patients in Italy. Study design of the 'Gruppo Italiano di Farmacovigilanza nell'Anziano' (GIFA).

The Italian Group of Pharmacoepidemiology in the Elderly (Gruppo Italiano di Farmacovigilanza nell'Anziano, GIFA) is a collaborative pharmacosurveillance study in hospitalized patients, sponsored by the Italian National Research Council (CNR) and the Italian Society of Gerontology and Geriatrics. It was founded in 1987 with the aim to constitute a multicentre research group to study quality of care and problems related to pharmacological therapy in the elderly. Until now the GIFA study has completed seven periodical surveys and enrolled a total of 28,411 hospitalized patients in 83 clinical centres.

The crystal structure of alpha-thrombin-hirunorm IV complex reveals a novel specificity site recognition mode.

The X-ray crystal structure of the human alpha-thrombin-hirunorm IV complex has been determined at 2.5 A resolution, and refined to an R-factor of 0.173.

Neuronorm is a potent and water soluble neurokinin A receptor antagonist.

We report here the synthesis and preliminary pharmacological characterization of a novel water soluble Neurokinin A receptor antagonist named Neuronorm. The synthesis was achieved in high yield by a combination of classical peptide synthesis methodologies, in both solution and solid phase. The pharmacological properties as neurokinin A receptor antagonist were assessed in in vitro experiments on rat vas deferens and guinea pig trachea, and were compared to those of MEN10627.

Specific interaction between bovine cyclophilin A and synthetic analogues of cyclolinopeptide A.

Like cyclosporin A, cyclolinopeptide A binds specifically bovine cyclophilin A, inhibiting its peptidyl-prolyl cis-trans isomerase activity. We describe here the protein interaction with several synthetic analogues of cyclolinopeptide A, which are either homodetic or disulphide bridged heterodetic cyclopeptides characterized by different ring dimensions, in terms of dissociation and inhibition constants evaluated by fluorescence and inhibition of the enzyme activity, respectively. Dissociation constants from fluorescence experiments are practically identical and about 20-fold lower than for cyclosporin A.