Impact of gender differences on the outcome of Alzheimer's disease.

BACKGROUND AND AIMS: Since little is known about the role of gender in the course of Alzheimer's disease (AD), a prospective epidemiological study was conducted to detect gender differences in relation to AD evolution and outcome. METHODS: Six hundred AD patients, 214 men and 386 women, first seen between September 2000 and December 2003, were enrolled; the follow-up period lasted until December 2008. RESULTS: The men had greater comorbidity and higher mortality than the women, who instead recorded more disability and longer survival. Survival curves showed that women reach partial loss of autonomy faster than men. Higher Neuropsychiatric Inventory scores at baseline showed a predictive value for loss of autonomy regardless of gender. Pharmacological treatment seems to have a protective role on disability and mortality. CONCLUSIONS: Gender influences disease evolution not only directly but also through other factors such as comorbidity.

DNp73alpha protects myogenic cells from apoptosis.

The P73 gene is transcribed from two promoters, P1 and P2, that direct the expression of multiple transactivation competent (TA) and dominant negative (DN) isoforms. TAp73 transcription factors mediate cell cycle arrest and/or apoptosis in response to DNA damage and are involved in developmental processes. P73 mRNA levels increase and the P1p73 promoter is upregulated during myogenic differentiation of C2C12 skeletal muscle satellite cells. The DNp73 proteins act as trans-repressors of p53- and p73-dependent transcription, and possess both antiapoptotic and pro-proliferative potential. Here, we show that DNp73alpha is expressed in proliferating C2C12 myoblasts, rapidly accumulates in differentiating myocytes and remains elevated in C2C12 myotubes. By combining transactivation assays and chromatin immunoprecipitation analysis, we could show that the upregulation of the P2p73 promoter during myogenic differentiation is mediated by the coordinated recruitment and activity of MyoD and p53/p73. Abrogation of DNp73 expression by specific siRNA led to a strong potentiation of the spontaneous apoptosis of C2C12 myoblasts induced to differentiate. Finally, unlike TAp73 that contributes to DNA damage-induced apoptosis of myotubes, endogenous DNp73 mediates the relative resistance of differentiated myotubes to DNA damage. Altogether, our findings identify DNp73alpha as an important target in designing strategies aimed at the potentiation of the regenerative potential of skeletal satellite cells.

Different geometric patterns of pacifiers compared on the basis of finite element analysis.

AIM: This study was carried out with the purpose to show on a virtual model of oral cavity the mechanical behaviour of different kinds of pacifiers with different pressure levels that can be likened to a condition of rest and deglutition. MATERIALS AND METHODS: Three different types of dummies, orthodontic- (A), cherry- (B) and drop- (C) shaped from an anatomical point of view, were inserted between the palate and the tongue in a virtual system by means of a finite element simulation. The palatal structure was recreated through tridimensional laser scanning, while the tongue structure was reconstructed by a software suitable for reproducing solids. Also the image of the pacifiers was developed by computer-aided scanning and reproduction. Suitable constraints were inserted and high and low pressure levels were exerted on these systems. FEA simulation allowed us to distribute the strain on the palate according to the different geometrical structures of the objects. RESULTS: Dummy A shows a more uniform and wider crosswise stress distribution with also a lesser load on the anterior palatal crest. Dummy B and C, on the contrary, show a more dot-like behaviour inducing a higher stress due to contact on restricted points. CONCLUSION: The characteristics of dummy A, although they have not been clinically investigated yet, seem to be the fittest ones to guarantee the maintenance of the transversal diameters of the premaxilla and reduce the risk of open bite.

GC-rich coding sequences reduce transposon-like, small RNA-mediated transgene silencing.

The molecular basis of transgene susceptibility to silencing is poorly characterized in plants; thus, we evaluated several transgene design parameters as means to reduce heritable transgene silencing. Analyses of Arabidopsis plants with transgenes encoding a microalgal polyunsaturated fatty acid (PUFA) synthase revealed that small RNA (sRNA)-mediated silencing, combined with the use of repetitive regulatory elements, led to aggressive transposon-like silencing of canola-biased PUFA synthase transgenes. Diversifying regulatory sequences and using native microalgal coding sequences (CDSs) with higher GC content improved transgene expression and resulted in a remarkable trans-generational stability via reduced accumulation of sRNAs and DNA methylation. Further experiments in maize with transgenes individually expressing three crystal (Cry) proteins from Bacillus thuringiensis (Bt) tested the impact of CDS recoding using different codon bias tables. Transgenes with higher GC content exhibited increased transcript and protein accumulation. These results demonstrate that the sequence composition of transgene CDSs can directly impact silencing, providing design strategies for increasing transgene expression levels and reducing risks of heritable loss of transgene expression.

Canola engineered with a microalgal polyketide synthase-like system produces oil enriched in docosahexaenoic acid.

Dietary omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), docosahexaenoic acid (DHA, C22:6) and eicosapentaenoic acid (EPA, C20:5) are usually derived from marine fish. Although production of both EPA and DHA has been engineered into land plants, including Arabidopsis, Camelina sativa and Brassica juncea, neither has been produced in commercially relevant amounts in a widely grown crop. We report expression of a microalgal polyketide synthase-like PUFA synthase system, comprising three multidomain polypeptides and an accessory enzyme, in canola (Brassica napus) seeds. This transgenic enzyme system is expressed in the cytoplasm, and synthesizes DHA and EPA de novo from malonyl-CoA without substantially altering plastidial fatty acid production. Furthermore, there is no significant impact of DHA and EPA production on seed yield in either the greenhouse or the field. Canola oil processed from field-grown grain contains 3.7% DHA and 0.7% EPA, and can provide more than 600 mg of omega-3 LC-PUFAs in a 14 g serving.

An assessment of hypothalamo-pituitary-adrenal axis functioning in non-depressed, early abstinent alcoholics.

Chronic alcohol consumption has been shown to be associated with abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis in humans. However, conflicting data exist in the literature, with particular regard to studies performed in actively drinking or withdrawn alcoholics; in addition, the frequent presence of depressive disturbances in such patients may importantly affect the neuroendocrine findings. In this study, we investigated HPA function in 12 male alcoholics, in whom the presence of depression and other possible confounding factors was excluded, during the first and second weeks after cessation of ethanol intake. The plasma corticotropin (adrenocorticotropic hormone, ACTH) and cortisol levels in response to both a stimulation test with human corticotrophin-releasing hormone (CRH; 100 micrograms IV) and an insulin (0.15 UI/kg IV)-induced hypoglycaemia (ITT) were measured; the cortisol response to a standard overnight dexamethasone (1 mg) suppression test (DST) was also tested. While the mean baseline ACTH and cortisol levels, measured in the morning (0800-0830 h), were not different from those of controls, ACTH and cortisol responses to the CRH test were markedly reduced (area of secretion p < .01 and p < .05, compared to controls). Similarly, the patient group showed an almost absent ACTH and cortisol release following insulin infusion (area of secretion p < .01 compared to controls, in either case). In four patients, non-suppression of plasma cortisol levels was seen on the DST, but no significant difference from normal suppressors was noted as far as the clinical features were concerned. These findings suggest that impaired hypothalamic and pituitary responsiveness, unrelated to depressive disturbances, occurs in recently withdrawn chronic alcoholics. While the possible influence of the alcohol withdrawal syndrome should be taken into account, such a pattern may be due to increased activity of the HPA axis, even in the face of preserved basal adrenal secretion. Whether these findings reflect a direct effect of sustained ethanol exposure on the components of the HPA axis, or a non-specific marker of impaired adaptation in chronic alcoholics, deserves further investigation.

Kidney depth measured by using 99Tcm-DMSA. Comparison with CAT scan: review of 50 measurements.

Measurement of kidney depths using computed axial tomographic (CAT) scans, considered as the gold standard, has been compared in 25 patients with depth measured using an isotopic method (99Tcm-DMSA). 99Tcm-DMSA underestimates renal depth in 78% of the cases (mean underestimation: 0.78 cm). The correlation coefficient between the two methods is 0.82. As a comparison, kidney depths calculated using Tonnesen's formula are also given and related to CAT scan results. The presence of renal morphological abnormalities in 18% of the studied kidneys allowed the authors to study their potential influence on 99TcmDMSA measurements. They do not seem to be very different from those obtained in morphologically normal kidneys. The different methods for kidney depth measurement described in the literature are briefly reviewed.

Correlation of 99Tcm-sestamibi SPECT with coronary angiography in general hospital practice.

One hundred and twenty-eight patients had a stress test with sestamibi injection and a coronarography within 2 months of the sestamibi study. Sestamibi studies were reconstructed using Hanning 0.65 and Wiener 1.0 filters; the latter improved the results significantly (P < 0.05). Significant correlations were found between sestamibi and coronarography: the sensitivity was 0.967 and the specificity was 0.711. Thus sestamibi is a very good compound, with excellent imaging quality, which is very sensitive for mild defects, even more sensitive than coronarography. Thorough studies of discrepancies show that they could be explained by reductions in coronary flow or myocardial reserve, even when the large epicardial vessels are disease free as occurs in various coronary involvements. A follow-up of positive patients with sestamibi and negative coronarography is absolutely necessary since this group of patients represents a 'risk' group. Moreover, sestamibi single photon emission computed tomographic accuracy is highly dependent on filter choice.

Spinal chondroma of the lumbar tract: case report.

BACKGROUND: Cartilage-forming tumors are benign cartilaginous tumors that rarely affect the spinal canal: they account for 2% of all spinal tumors and 2.6% of all benign bone tumors. Pathologically, they may be classified as chondromas, osteochondromas, chondroblastomas, and chondromyxoid fibromas. This oncotype may remain asymptomatic (it is confined within the vertebral structure) or may present as a hard paravertebral swelling (it invades the paravertebral structures) or more rarely, with a slowly-developing neurologic syndrome (it extends into the vertebral canal). METHODS: Thirty-one cases have been reported (including our case) of benign cartilage-forming tumors localized in the lumbar column. Only three cases of chondroma of the lumbar spine presented with lumbar radicular pain. We report a fourth case and review clinical and radiologic characteristics of these lesions. RESULTS: Eleven out of the 31 cases were diagnosed as chondromas, 17 as osteochondromas, while in three cases the histopathologic diagnosis was not reported. Seventeen cases originated from the neural arch, seven from the vertebral body, two from the spinous process, and in five cases the exact localization was not reported. This tumor is more frequent in males (21 cases out of 31), than in females (five cases); in five cases the sex was not reported. Mean duration of symptoms was 23 +/- 5.1 months (range: 1-96); chondromas have a short clinical history before diagnosis (13.8 +/- 3.4 months) compared to osteochondromas (28.6 +/- 7.6). Clinical presentation with local swelling is reported in 10 cases, in 10 cases local pain without radicular irradiation, in six cases lumbar pain with sciatica, in two cases signs and symptoms of cord compression, one case of cauda syndrome, while in four cases no clinical details are reported. Among the six cases presenting with sciatica, four were chondromas (in all cases the L4 level was involved), and one osteochondroma, while in one case the histopathologic diagnosis was not reported. CONCLUSION: Computed tomography is important and indispensable for preoperative diagnosis, giving a precise indication of tumor extent and location and its relationship to the adjacent structures; while MRI is helpful in detecting patterns related to histologic malignancy. It is important to examine the whole tumor histologically because it is known that there may be small areas that show signs of malignancy; thus is more likely in chondromas than osteochondromas.

Effect of exercise on the leg distribution of C15O2 and 15O2 in normals and in patients with peripheral ischemia: a study using positron tomography.

In order to evaluate regional muscle blood flow and oxygen utilization, we study with positron emission tomography (PET) the distribution of C15O2 and 15O2 in 17 subjects: 5 normals (24 +/- 3 years) and 12 patients (63 +/- 13.5 years). C15O2 and 15O2 are inhalated with a steady-state technique. Positron tomograms are recorded in supine position at the greatest diameter of the leg. Exercise consists in simultaneous ankle flexions. In all normals, C15O2 and 15O2 are distributed homogeneously and symmetrically in both legs. At rest, they concentrate in the region of vascular pedicle. After exercise, C15O2 and 15O2 are electively distributed in the anterolateral region of the leg. In patients, this pattern of distribution is similar but asymmetrical. Moreover, the regional uptake of C15O2 and 15O2 often dissociates. In conclusion, C15O2 and 15O2 allow to study repeatedly muscle blood flow and oxygen utilization in patients with peripheral ischemia, both at rest and after exercise. The broad spectrum of pathological changes observed in this study needs further metabolic investigations.

Neuropsychological changes in demented patients treated with acetyl-L-carnitine.

The study was carried out on 24 patients suffering from mild to moderate dementia. The diagnosis of dementia was made according to DMS III criteria. Patients with cerebrovascular pathologies were excluded by using Hachinski Ischaemic Score less than or equal to 4 and computerized tomography parameters. Patients with depression (Hamilton Rating Scale for Depression greater than or equal to 18) were excluded. All the patients, after a wash-out period of two weeks were treated on a simple blind method with acetyl-L-carnitine (No. = 12 patients) and piracetam (12 patients) by intravenous route (two weeks) followed by an oral one for further 10 weeks. A battery of clinical neuropsychological tests was applied to evaluate the cognitive, attentive and behavioural aspects. The results, analysed by non-parametric variance analysis (Friedman Test) show a statistically significant improvement of the behavioural profile, of attention and of psychomotricity in the patients treated with acetyl-L-carnitine. No significant improvement was found in the piracetam group.

Alcoholic abstinence syndrome: short-term treatment with metadoxine.

The effects of metadoxine (pyrrolidone carboxylate of pyridoxine), a compound with central benzodiazepine-like properties, were evaluated in two groups of chronic alcoholics (inpatients) presenting a mild withdrawal syndrome. According to a double-blind study design 20 patients received metadoxine 900 mg twice daily eluted in 500 ml of saline infusion, while 20 (the control group) were given 500 ml of saline infusion twice daily with equivalent doses of pyridoxine (40 mg/die) every morning over a 10-day period. The results indicate that metadoxine treatment was able to control alcohol abstinence, thus allowing a reduction in the needs for standard benzodiazepine therapy. The central activity of gamma-aminobutyric acid of this compound might play a crucial role in the clinical effects demonstrated.

Pramiracetam effects on scopolamine-induced amnesia in healthy volunteers.

Pramiracetam has been evaluated for its potential antiamnesic properties in scopolamine-induced amnesia in healthy volunteers. Two groups of twelve males, 18-42 and 55-65 years old, respectively, were randomly assigned to oral treatment with pramiracetam (600 mg twice a day) or with placebo for 10 consecutive days. On day 11 each subject was injected intramuscularly with scopolamine hydrobromide (0.5 mg). Before scopolamine injection and then 1, 3 and 6 h after it, subjects were administered the following psychometric tests: simple and choice visual reaction times, digit symbol substitution test, Rey's 15 words test for short and long term verbal memory. Scopolamine significantly impaired episodic memory and selective attention tests in both scopolamine and placebo groups. Instead visuo-motor and incidental learning measures were unaffected. Pramiracetam, when compared to placebo, was able to partially reduce the amnesic effects induced by scopolamine both in young and old subjects.

Long-term idebenone treatment of vascular and degenerative brain disorders of the elderly.

A multicentre study with an open experimental design was carried out on 118 patients suffering from mild to moderate cognitive decline due to cerebrovascular and degenerative disorders (chronic cerebrovascular disorders, CCVD; multi-infarct dementia, MID; aging brain, AB; dementia of Alzheimer's type, DAT). All patients, after a wash-out period of 3 weeks, were treated with idebenone (45 mg twice daily by oral route) for a period of 6 months. Behavioral and cognitive measures (Sandoz Clinical Assessment of Geriatrics, SCAG; Serial Learning Test) were applied to evaluate the long term therapeutical aspects. The results, analyzed by multivariate analysis of variance and chi2 test, showed a significant improvement of the cognitive profile in all patients, more evident in CCVD and AB groups. No remarkable side-effects were found in all groups of patients, thus confirming good tolerability of idebenone.

[++Scintimammography: a new imaging technique for diagnosis and follow-up of breast cancer]. / Apport de la mammoscintigraphie 99m Tc MiBi dans le diagnostic et le suivi des cancers du sein.

99m Tc MiBi has emerged as a new imaging technique for primary breast carcinomas. The aim of this study was to analyze the diagnostic performance and the additional information provided by scintimammography (SMN). Two hundred and forty consecutive women referred to surgery for abnormalities breast or suspicious breast cancer were scanned before surgery. Sensitivity and specificity were respectively 92% and 53%. PPV: 77.5% and PVN: 79.3%. All false negative scans occurred in cancers 1 cm. SMN detected multiple foci of uptake in the same breast in 13%, that were all confirmed to be multifocal disease and histology. Controlateral focal uptake was also detected; at this time 5/27 are confirmed to be bilateral breast neoplasms; 22 patients are in follow-up. SMN is reliable in the diagnosis of breast cancer and also with difficult cases of mammography. Moreover, SMN provides additional qualitative information in 19.6% of breast carcinomas, such as chest wall infiltration, multifocal or bilateral breast cancer.

[Alcohol withdrawal syndrome. Effects of short-term treatment with dapiprazole]. / Sindrome da astineza alcoolica. Effetti del trattamento "short-term" con dapiprazolo.

A study on dapiprazole, a new psychotropic agent, in the treatment of patients during the alcohol withdrawal syndrome, is reported. On the basis of evaluations made on the severity of the physical and psychic symptoms of withdrawal, the conclusion is drawn that the new psychotropic agent, administered at gradually increasing doses of 40 to 90 mg/kg for 7 days, completely controls the clinical symptomatology at least in 70% of the cases treated.

[Regional blood flow and oxygen consumption in the leg muscles of normal subjects and in those with arterial insufficiency. Study of the distribution of C15O2 and of 15O2 using positron emission tomography]. / Débit sanguin régional et extraction de l'oxygène dans les muscles de la jambe chez le sujet normal et l'insuffisant artériel. Etude de la distribution du C15O2 et de l'15O2 par tomographie à émission de positons.

We first studied the distribution of radioactivity during continuous inhalation of C15O2 and 15O2 in traverse tomograms of the greatest diameter of legs, at rest and immediately after exercise (ankle flexions). C15O2 and 15O2 were distributed homogeneously and symmetrically in both legs of normal subjects at rest. The activity accumulated in the anterolateral region after exercise. In patients, this pattern of distribution was similar but asymmetrical, depending on the arterial pathology. No systematic distribution of either C15O2 or 15O2 was observed. In a second step, we studied quantitatively blood flow (F), oxygen uptake (R) and oxygen extraction (E) in 11 subjects: 5 normals (23 +/- 1 years) and 6 patients (60 +/- 11 years) suffering from unilateral intermittent claudication. We used the bolus inhalation technique of C15O2 and 15O2. In the normal leg at rest, ranges were 2.5 to 8.0 ml/min.hg for F, 0.9 to 21.3 mumol/min.hg for R and 3.6 to 33.4% for E. In the pathological leg at rest, ranges were 3.7 to 11.3 ml/min.hg for F, 3.8 to 10.6 mumol/min.hg for R and 7.1 to 24.5% for E. After exercise, ranges were 6.4 to 62.8 ml/min.hg for F, 66.0 to 386.3 mumol/min.hg for R and 29.2 to 89.5% for E in both legs. There was no straight difference between normal and pathological legs soon after exercise. This study allows us to expect that the demonstration of such a difference implies a longer delay of data acquisition following the slow post-ischemia recovery.

Long-Term Nicergoline Treatment of Mild to Moderate Senile Dementia : Results of a Multicentre, Double-Blind, Placebo-Controlled Study.

The efficacy and tolerability of nicergoline were evaluated in a long-term, double-blind, placebo-controlled trial. 108 patients, fulfilling DSM III-R criteria for mild to moderate senile dementia of degenerative, vascular or mixed origin, were selected from a pool of outpatients attending five Italian neurological centres and randomised to receive nicergoline 30mg twice daily (54 patients) or placebo (54 patients) for 12 months. Treatment efficacy on cognitive and behavioural performances was assessed by the Sandoz Clinical Assessment Geriatric scale (SCAG) and Mini Mental State Examination (MMSE), at baseline and after 3, 6, 9 and 12 months of treatment. Investigators and patients or caregivers provided a global evaluation of treatment outcome at study end. The efficacy analysis was carried out on 101 patients (51 nicergoline; 50 placebo) who completed the 12-month study. At study end, the SCAG total score and its clusters showed statistically significant improvement in the nicergoline-treated group compared with placebo-treated patients. The MMSE total score was maintained with nicergoline treatment. Global treatment evaluations, both by physician and patients, were consistently in favour of nicergoline (p < 0.001). Nicergoline was well tolerated; incidence of adverse events (7% in the nicergoline and 2% in the placebo group), withdrawals and haemodynamic changes were comparable with placebo.

[Can benign and malignant thyroid nodules be differentiated with thallium 201?]. / Le thallium 201 permet-il de différencier le nodule thyroïdien bénin du nodule malin?

The merits of Thallium 201 radionuclide scanning of the thyroid mentioned as soon as 1976 by PALERMO have been confirmed in the 16 last studies published in the international literature. Over 1601 examinations, authors showed that any cold nodule (Tc 99 m or I 123) which preferentially fixes Thallium 201 as compared to surround thyroid tissue must be operated since some of them are thyroid cancer carriers, some others are carriers of a traditional follicular adenoma or Hurthle-cell adenoma, or a follicular adenoma associated with varied cell atypisms which make difficult the diagnosis between benign and malignant nodules. The analysis of the results published show a 91.3% sensitivity of this diagnosis test, all analysis methods being considered. In case of negative test, it allows eliminating the cancer risk by more than 97% (negative predictive value). Such an examination--as opposed to a cytology test on the isolated nodule only--is valid for any type of nodule, being isolated, multiple or a multinodular goitre where the degeneration risk is close to, or even higher than, that of isolated nodules (4, 22).

[Economic analysis of diagnostic and therapeutic methods in cases of cold thyroid nodules]. / Analyse économique des approaches diagnostiques et thérapeutiques du nodule froid de la thyroïde.

This article studies how two diagnostic tests (cytological puncture and 201thallium scanning) can be combined to obtain a more efficient approach of cold thyroid nodules. Diagnostic and therapeutic approaches are compared on the basis of four criteria: financial cost (immediate and delayed), number of labelled cancers, pre- and postoperative death rates and number of complications.