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Biomedical subjects

C Pedone

Publications and source records attributed to C Pedone.

At least 37 records · Page 2Linked to original sources

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. To this end, we used the GIFA database that includes patients admitted to academic medical centres throughout Italy between 1988 and 1997. We studied 5061 patients over 65 years of age selected among a population of 28 411, based on the diagnosis of arterial hypertension at discharge. The use of ACE-inhibitors has been raising steadily through the years, and they are the agents most commonly used since 1996. Calcium channel blockers showed a similar trend and were the top prescribing drug until 1995; afterwards, the documentation of potentially severe side effects has resulted in a nearly 20% reduction of their use. Beta-blockers have remained unpopular throughout the decade. Instead, the prescription of diuretics as a class showed a biphasic trend; an initial decrease with a prolonged steady state and a more recent raise. However, at a separate analysis, it was a evident that a progressive increase of the use of loop diuretics since 1988 has been paralleled by a nearly 50% reduction of thiazides prescriptions. Loop diuretics were more likely to be prescribed to older individuals, those with cardiac heart failure, coronary heart disease and high creatinine level. In contrast, independent predictors of thiazides use were female gender, good functional status, preserved renal function, and absence of cardiovascular comorbidity. In conclusion, despite continued recommendations to use thiazides diuretics for the treatment of hypertension among older individuals, their use has been declining steadily between 1988 and 1997. A possible explanation is that the choice to prescribe a thiazides diuretic is influenced by age, functional status and comorbidity.

Age Factors↗

Molecular interactions with nuclear factor kappaB (NF-kappaB) transcription factors of a PNA-DNA chimera mimicking NF-kappaB binding sites.

The decoy approach against nuclear factor kappaB (NF-kappaB) is a useful tool to alter NF-kappaB dependent gene expression using synthetic oligonucleotides (ODNs) carrying NF-kappaB specific cis-elements. Unfortunately, ODNs are not stable and need to be be extensively modified to be used in vivo or ex vivo. We have previously evaluated the possible use of peptide nucleic acids (PNAs) as decoy molecules. The backbone of PNAs is composed of N-(2-aminoethyl)glycine units, rendering these molecules resistant to both nucleases and proteases. We found that the binding of NF-kappaB transcription factors to PNAs was either very low (binding to PNA-PNA hybrids) or exhibited low stability (binding to PNA-DNA hybrids). The main consideration of the present paper was to determine whether PNA-DNA chimeras mimicking NF-kappaB binding sites are capable of stable interactions with proteins belonging to the NF-kappaB family. Molecular modeling was employed for the design of PNA-DNA chimeras; prediction of molecular interactions between chimeras and NF-kappaB nuclear proteins were investigated by molecular dynamics simulations, and interactions between PNA-DNA chimeras and NF-kappaB proteins were studied by gel shifts. We found significant differences between the structure of duplex NF-kappaB PNA-DNA chimera and duplex NF-kappaB DNA-DNA. However, it was found that these differences do not prevent the duplex PNA-DNA chimera from binding to NF-kappaB transcription factors, being able to suppress the molecular interactions between HIV-1 LTR and p50, p52 and nuclear factors from B-lymphoid cells. Therefore, these results demonstrate that the designed NF-kappaB DNA-PNA chimeras could be used for a decoy approach in gene therapy.

Animals↗

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 77.8 +/- 7.1 years, range 65-100 years, males 49.8%) consecutively admitted to 69 General Medicine and Geriatrics wards over a 4-month period were grouped by combining two dichotomous factors (Carlson's score > 4: definite or possible diagnosis of CHF; Carlson's score < 5: unlikely diagnosis of CHF; in-hospital adoption of digitalis therapy: yes or no) as follows: Group A: Carlson's score > 4, digitalis (n = 413); Group B: Carlson's score > 4, no digitalis (n = 260); Group C: Carlson's score < 5, digitalis (n = 104); Group D: Carlson's score < 5, no digitalis (n = 462). Variables significantly distinguishing groups were entered into a discriminant analysis aimed at assessing the group specificity of individual clinical profiles. RESULTS: Use of digoxin at home, atrial fibrillation, older age, and comorbidity (mainly COPD and chronic renal failure) characterized most of the patients given digoxin with or without a definite diagnosis of CHF. Clinical profiles of groups A, B, and C largely overlapped. CONCLUSION: Age, historical use of digitalis, and comorbidity might lead to seemingly incongruous digitalis prescription. The choice of adopting digitalis therapy cannot be reliably predicted on the basis of clinical variables only. Presently unexplored physician-related factors, such as cultural background, likely outweigh clinical variables in prompting digitalis prescription.

Aged↗

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. The association between groups of variables (demographics, comorbid conditions, medications, and objective tests, including the Hodkinson abbreviated mental test) and functional disability (as indicated by need for intensive assistance in at least one of Katz' activities of daily living) was first analysed using separate age and sex adjusted logistic regression models. Those variables, significant at a p<0.1 level in these models, were simultaneously entered into an age and sex adjusted summary regression model. Among 1583 patients suitable for analysis, cognitive dysfunction (as detected by abbreviated mental test score <7) was detected in 265/461 disabled patients, and in 150/1122 independent subjects (p<0.0001). According to logistic regression analysis, cognitive dysfunction was associated with disability (OR=6.49; 95% CI=4.39-9.59) after adjusting for potential confounders.Thus, cognitive dysfunction in patients with heart failure is independently associated with disability, which currently represents an overwhelming medical and financial problem to patients, caregivers, and public health services. As early recognition and treatment of low cardiac output states might reverse cognitive dysfunction, cost effective treatment for heart failure should include systematic diagnostic and therapeutic approaches to cognitive dysfunction.

Aged↗

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+/-11.1 years (mean+/-SD), 66.1% males, consecutively hospitalized in 32 wards of General Medicine and 31 of Geriatrics in acute care hospitals for exacerbated COPD in 10 bimonthly periods between 1988 and 1997. On admission, patients underwent a structured assessment of demographic data, nutritional status, cognitive and physical functions, comorbidity, and pharmacological therapy in the two weeks prior to admission. Patients were grouped according to whether their length of stay exceeded or not the 75th percentile of stay distribution in each bimonthly period. Variables univariately distinguishing groups were entered into a logistic regression analysis having long-stay as the dependent variable. Living alone (Odds Ratio 1.33, 95% Confidence Limits 1.03-1.70), use of more than 3 drugs prior to admission (OR 1.29, CL 1.09-1.51), use of drugs with respiratory depressant properties prior to admission (OR 1.24, CL 1.05-1.46), and the presence of more than 3 comorbid diseases (OR 1.88, CL 1.61-2.19) were independent correlates of long-stay. Age did not predict length of stay. In conclusion, selected health outcomes and indicators of disease severity, but not age, target COPD patients at risk of long-stay. Research is needed to verify whether these data can help program interventions aimed at shortening length of stay and, thus, at reducing annual hospitalization costs of the elderly.

Aged↗

Dose-related impact of alcohol consumption on cognitive function in advanced age: results of a multicenter survey.

BACKGROUND: Moderate alcohol consumption has been associated in several studies with decreased risk of cardiovascular and cerebrovascular events; however, available data on the effects of alcohol intake on cognitive functioning are conflicting. We assessed the association between alcohol consumption and cognitive impairment in a series of older subjects enrolled in a multicenter pharmacoepidemiology survey. METHODS: The association between average alcoholic intake and cognitive performance was assessed in 15,807 patients admitted to participating centers during the survey periods. Demographic variables, comorbid conditions, medications, and objective tests that were associated with cognitive impairment (as indicated by a Hodkinson Abbreviated Mental Test score <7) in separate logistical regression models were examined as potential confounders in a summary model. RESULTS: Cognitive impairment was detected in 1693 (19%) of 8755 drinkers and 2008 (29%) of 7052 nondrinkers (Fisher's exact test, p < 0.0001). After adjusting for potential confounders, alcohol consumption was associated with decreased probability of cognitive impairment (odds ratio, 0.75; 95% confidence interval, 0.66-0.85). The relationship between drinking level and cognitive dysfunction was nonlinear, because the probability of cognitive impairment was decreased for moderate alcohol use as compared with abstinence, but it was increased for daily consumption exceeding one wine-equivalent liter among men and 0.5 liter among women. This nonlinear association persisted when cerebrovascular and Alzheimer's disease were considered separately. CONCLUSIONS: Alcohol abuse is associated with increased prevalence of cognitive dysfunction among older subjects; however, a daily alcohol consumption of less than 40 g for women and 80 g or less for men might be associated with a decreased probability of cognitive impairment. This possible protective effect of alcohol consumption should be further assessed by prospective studies.

Aged↗

Serum magnesium levels and cognitive impairment in hospitalized hypertensive patients.

We performed this cross-sectional case control study to investigate the association between low serum magnesium levels and cognitive impairment in hypertensive hospitalized patients. The study was carried out in general medical care units at 81 hospitals participating in the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study throughout Italy, and a total of 1058 patients with diagnoses of hypertension at the discharge were studied. The occurrence of cognitive impairment at discharge was the primary outcome of our study. Cognitive impairment was ascertained using the Hodkinson Abbreviated Mental Test (HAMT). Sociodemographic variables, body mass index, laboratory parameters, comorbidity, use of antihypertensive drugs and number of drugs were considered as potential confounders. Twenty-nine percent of the selected hypertensive patients were classified as having cognitive impairment. In univariate analysis, older age, female sex, and low educational level showed a significant trend for association to cognitive impairment. Moreover the proportion of subjects with cognitive impairment decreased with increasing alcohol consumption, and the prevalence of ex smokers and smokers was significantly lower in patients with cognitive impairment. The lower tertiles for serum albumin and creatinine clearance were more frequent among patients with cognitive impairment, and the lower tertile for serum magnesium levels was significantly more frequent in these patients. Number of drugs was slightly lower in cognitively impaired patients, while number of diagnoses and length of hospital stay were higher in these subjects. In the multivariate logistic regression analysis cognitive impairment decreased with increasing education level (highest education: OR 0.11; 95 per cent CI 0.05-0.25). The lower tertile for serum albumin (< 3.5 g/dl) was significantly associated to cognitive impairment (OR 2.14; 95 per cent CI 1.31-3.49), as well as the lower tertiles for serum magnesium (0.74-0.86 mmol/L: OR 1.54; 95 per cent CI 1.06-2.22; < 0.74 mmol/L: OR 1.75; 95 per cent CI 1.13-2.72]. Our results demonstrate the existence of a significant association between magnesium imbalance and cognitive impairment. These data suggest that the assessment of magnesium status may be of some relevance in hypertensive subjects with cognitive disorders.

Aged↗

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 2.6 A resolution by a multiple wavelength anomalous diffraction experiment on a seleno-methionine derivative. EST2 presents a canonical alpha/beta hydrolase core, shielded at the C-terminal side by a cap region built up of five helices. It contains the lipase-like catalytic triad, Ser155, His282 and Asp252, whereby the nucleophile is covalently modified. This allows an unambiguous view of the putative active site of EST2, detecting the oxyanion hole, in whose formation the amino acid sequence motif His81-Gly82-Gly83-Gly84 is involved, and the hydrophobic binding pocket for the acyl chain. The structural model here reported provides the first example of a transition state analogue of an esterase/lipase belonging to the HSL group, thus affording useful information for the design of medical inhibitors. Moreover, as the first X-ray structure of a thermophilic carboxylesterase, the comparison with its mesophilic homologue, the Brefeldin A esterase (BFAE) from Bacillus subtilis, allows the identification of putative determinants of thermal stability.

Amino Acid Sequence↗

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. METHODS: We analyzed data from a large collaborative observational study group, the Italian Group of Pharmacoepidemiology in the Elderly (GIFA), that collected data on hospitalized patients. A total of 18,316 patients consecutively admitted to 79 clinical centers during 5 different surveys in 1998, 1991, 1993, 1995, and 1997 were enrolled in the present study. The main outcome measure was the relative hazard ratio of death for different levels of BMI. RESULTS: Mortality rate was lowest among men and women with BMIs from 25.0 through 27.4 kg/m(2) (relative risk, 0.24; 95% confidence interval, 0.15-0.38). The graphed relationship between BMI and mortality in younger patients was hyperbolic, with increased death rates at the lowest and highest BMI rankings. On the contrary, the older patients showed an increased death rate at the lowest BMIs with only a slight elevation at the highest BMIs (>35 kg/m(2)). CONCLUSIONS: Our results suggest that BMI, a simple anthropometric measure of nutritional status, is an important predictor of mortality among young and old hospitalized patients. Even when controlling for clinical and functional variables, a low BMI remained a significant and independent predictor of shortened survival. Furthermore, the finding of the high BMI associated with minimum hazard in elderly subjects supports some past findings and opposes others and, if confirmed, has important implications for geriatric clinical guidelines.

Adult↗

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. 404(5) A, c = 21.508(4) A, and beta = 90.83(6) degrees, with two independent cyclic molecules in the asymmetric unit, two DMSO molecules, and three water molecules. The structure has been solved using the half and bake procedure by Sheldrick, and refined to final R1 and wR2 indices of 0.0613 and 0.1534 for 9867 reflections with I > 2sigma(I). This cyclic peptide, a deletion analogue of the naturally occurring cyclic nonapeptide cyclolinopeptide A [c(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val), CLA] has been designed to study the influence of the ring size reduction on the conformational behavior of CLA and more in general to obtain structural information on asymmetric cyclic octapeptides. The compound exhibits, in the solid state, a "banana-twisted" conformation with a cis peptide bond located between the two proline residues. Five intramolecular H bonds stabilize the structure: one type VIa beta-turn, two consecutive type III/I beta-turns, one gamma-turn, and one C(16) bend. The structure has also been compared with either the solution structure previously reported by us and obtained by nmr and computational analysis, and with solid state structural data reported in the literature on cyclic octapeptides.

Amino Acid Sequence↗

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. We examined the consumption of the four main antihypertensive classes of drugs (beta-blockers, diuretics, calcium channel blockers and ACE- inhibitors). In-hospitalization data from the GIFA (Gruppo Italiano di Farmacoepidemiologia nell'Anziano) database were used. During the period from 1988 to 1995, the most frequently prescribed antihypertensive drugs were calcium channel blockers (47%) followed by diuretics (37%), ACE-inhibitors (33%) and beta-blockers (5.5%). Changes over time in the use of these drugs were analysed: ACE-inhibitors had the greatest increase in use over time. Calcium channel blockers, ACE-inhibitors and beta-blockers were usually prescribed to the youngest patients (aged <65 years), while diuretics to the oldest. Calcium channel blockers were prescribed to 60% of patients with myocardial infarction and to 55% of those with congestive heart failure. In conclusion, our study demonstrates that the Italian physicians very often prescribe drugs like calcium channel blockers and ACE-inhibitors. Among these pharmacological agents, enalapril (twice per day) and slow release calcium channel blockers are the most frequently prescribed drugs.

Adrenergic beta-Antagonists↗

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. Among these participants, 1,076 patients started taking calcium antagonists during their hospital stays. Demographic variables, comorbid conditions, medications, and objective tests that were associated with incident hemoglobin loss in separate age- and sex-adjusted logistic regression models were examined as potential confounders in a summary model. Higher risk for gastrointestinal bleeding was defined by diagnosis, treatment for peptic disease, or both. RESULTS: Hemoglobin decrease was detected in 24% of participants who started treatment with calcium antagonists and in 19% of other patients (P < .0001). In addition, use of calcium antagonists was independently associated with increased probability of hemoglobin loss (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.03 to 1.45; P = .018) after adjusting for potential confounders. Treatment with calcium antagonists was associated with hemoglobin loss in patients with higher baseline risk for gastrointestinal bleeding (OR, 1.67; 95% CI, 1.26 to 2.22; P < .0001) but not among other participants (OR, 1.02; 95% CI, 0.82 to 1.25). CONCLUSION: Starting treatment with calcium antagonists is associated with a reduction in hemoglobin levels during a hospital stay. However, the increased risk of hemoglobin loss seems to be limited to patients with diagnosis or symptoms of peptic disease.

Aged↗

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. Therefore, antisense and antigene PNAs have been synthetized and characterized. The major issue of the present paper is to describe some computational procedures useful to compare the behaviour of PNA double stranded molecules and PNA/DNA hybrids with the behaviour of regular DNA duplexes in generating complexes with DNA-binding proteins. The performed computational analyses clearly allow to predict that the lack of charged phosphate groups and the different shape of helix play a critical role in the binding efficiency of NF-kappaB transcription factors. These computational analyses are in agreement with competitive gel shift and UV-cross linking experiments. These experiments demonstrate that NF-kappaB PNA/PNA hybrids do not interact efficiently with proteins recognizing the NF-kappaB binding sites in genomic sequences. In addition, the data obtained indicate that the same NF-kappaB binding proteins recognize both the NF-kappaB DNA/PNA and DNA/DNA hybrids, but the molecular complexes generated with NF-kappaB DNA/PNA hybrids are less stable than those generated with NF-kappaB target DNA/DNA molecules.

Base Sequence↗

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. Demographic variables, comorbid conditions, medications, and objective tests that were associated with incident hypokalemia in separate age- and sex-adjusted logistic regression models were examined as potential confounders. RESULTS: Among patients with normal baseline serum potassium, the factors of age, presence of coronary disease or diabetes, comorbidity, the use of ACE inhibitors, loop diuretics, digitalis, corticosteroids, or insulin, and baseline serum potassium were associated with incident hypokalemia in initial models. After these variables were adjusted for, age (for each decade, odds ratio = 1.30; 95% confidence interval = 1.17-1.46; p < .0001) was associated with incident hypokalemia. The use of parenteral (2.30; 1.53-3.46; p < .0001) but not oral (1.16; 0.79-1.69; p = .44) loop diuretics was associated with hypokalemia. Eventually, age was associated with hypokalemia when the summary regression model was analyzed in patients taking loop diuretics (1.33; 1.03-1.71; p = .027), as well as in those taking intravenous loop diuretics only (1.84; 1.25-2.70; p = .002). CONCLUSIONS: Older age is independently associated with the in-hospital development of hypokalemia, particularly among patients taking loop diuretics. Monitoring of serum potassium levels is therefore advisable when older patients are treated with these agents.

Age Factors↗

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. For each tumor, we determined the percentage of tumor cells showing PTEN immunoreactivity in the most cellular regions of the tumor specimen. In both astrocytomas and oligodendrogliomas, there was an inverse relationship between the percentage of PTEN+ cells and malignancy grade, consistent with a role for PTEN as a tumor suppressor gene, the expression of which declines during glioma progression. In nonneoplastic tissue, PTEN was expressed in human fetal brain at 16, 23, and 27 weeks' gestation, but not in adult brain, indicating that PTEN is developmentally regulated in the CNS. In 21 glioblastomas multiforme, we correlated PTEN protein expression with PTEN gene sequence. Although PTEN-mutant tumors showed significantly diminished PTEN protein expression compared with wild-type cases, suppressed expression of PTEN is more prevalent than predicted from mutation frequencies.

Adolescent↗

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 database of the study contains approximately 174,000 in-hospital drug prescriptions, approximately 88,000 discharge diagnoses and a great deal of data on topical geriatric items such as cognitive performance, disability, comorbidity, adverse drug reactions and incontinence. This paper describes the general organization and the methods of the GIFA study and shows in detail the type of data collected.

Adverse Drug Reaction Reporting Systems↗