Long-term use of pharmacological treatment in Alzheimer's disease: a retrospective cohort study in real-world clinical practice.

PURPOSE: To assess the impact of long-term use of different drugs commonly prescribed in Alzheimer's disease (AD) on its clinical course and to identify clinical and therapeutic factors associated with a delay in AD progression. METHODS: We retrospectively enrolled 50 patients visited at the Neurology Unit, Careggi University Hospital (Florence), followed for at least 24 months. AD diagnosis was made according to clinical diagnostic criteria for probable/possible AD dementia, always supported at least by one biomarker. Clinical features, MMSE scores evaluated at diagnosis and every 6 months, and AD drugs used for at least 6 months, were recorded. Cox regression analysis was performed to estimate the hazard ratio (HR) for AD progression, assuming as the "final event," the progression to a more severe disease stage, defined as the achievement of an MMSE score less than 10. RESULTS: At baseline, the median MMSE score was 22. During follow-up (median of 41 months), 56% of patients progressed to a more severe disease stage. The use of memantine, either alone (HR 0.24; 95% CI 0.09-0.60) or combined with acetylcholinesterase inhibitors (HR 0.35; 95% CI 0.14-0.88) and a higher MMSE score at baseline (HR 0.82; 95% CI 0.70-0.96) were associated with a significantly lower risk of AD progression. CONCLUSION: Nowadays, effective disease-modifying therapy for AD is missing. Nevertheless, when the diagnosis is established, our results support the advantage of long-term use of available pharmacological treatments, especially in combination, in delaying AD progression to its more severe disease stage.

DTI parameters in neonates with hypoxic-ischemic encephalopathy after total body hypothermia.

BACKGROUND AND PURPOSE: MR imaging provides means for discriminating different patterns of Hypoxic-ischemic encephalopathy (HIE) and may distinguish most severe cases from less severe but is unable to predict long-term outcome. Diffusion tensor imaging (DTI) offers information for a more complete characterization of HIE. The purpose of this study is to compare the modifications of DTI parameters in newborns one week and six months following total-body cooling to healthy controls. METHODS: Forty-seven cooled newborns were studied with MRI, 20 underwent follow-up at 6 months. 12 healthy newborns and nine children at 6 months were enrolled as control groups (HC). Inferior Longitudinal Fasciculus (ILF), Corpus Callosum Fasciculus (CCF), Corticospinal Tract (CST), Optical Tract (OT), Optic Radiation (OR) were generated in all subjects. DTI parameters were evaluated in basal ganglia (BG), thalamus (TH) and tracks. Statistical analysis was performed with MANOVA. RESULTS: In newborns HIE versus HC, there were significantly lower fractional anisotropy (FA) on OR and CST and higher axial diffusivity (AD), apparent diffusion coefficient (ADC) and radial diffusivity (RD) values on CST, BG and TH in HIE-N. At 6 months there were no significant grouping effects. The analysis showed a significant increase of FA, decrease of ADC, AD, RD after 6 months for HIE and HC. CONCLUSIONS: We observed modifications of parameter values in HIE newborns vs HC; however normalization of values at 6 months suggests that changes of parameters cannot be considered early biomarkers for evaluation of therapeutic hypothermia in newborns with moderate HIE and normal conventional MRI.

'Frequently recurring' nocturnal polyuria is predictive of response to desmopressin in monosymptomatic nocturnal enuresis in childhood.

INTRODUCTION: The nocturnal polyuria is considered a significant predictive value for response to desmopressin. The cutoff value useful to define nocturnal polyuria is still a matter of debate. Moreover, it is current notion that maximal voided volume (MVV) could be used as a predictor for desmopressin response. OBJECTIVE: The objective of this study was to assess the impact of different definitions of nocturnal polyuria (and of its frequency) and MVV in predicting the response to desmopressin. STUDY DESIGN: A total of 103 patients with frequent monosymptomatic nocturnal enuresis (≥4 wet nights/week) were enrolled. A bladder diary over a 4-day period was collected. The MVV was defined as the highest micturition volume detected at bladder diary. Nocturnal diuresis was measured in 5 wet nights. Then, patients were administered with 120 mcg of sublingual desmopressin. After 2 months, if there was no complete response, the dose was increased to 240 mcg. Nocturnal polyuria was defined as follows: 1.Definition 1: nocturnal urine production >130% of the expected bladder capacity (EBC). 2. Definition 2: >100% EBC. 3. Definition 3: > 20×(age + 9) mL. The primary outcome was 'response to desmopressin' after 3 months of treatment. RESULTS: Fifty-three patients responded to desmopressin. Comparing the responses to desmopressin on the basis of the three definitions of nocturnal polyuria, no significant difference was found. There was no cutoff value of nocturnal polyuria expressed as %EBC useful in providing a significant receiver-operating characteristic (ROC) curve. The area under the ROC curve for MVV expressed as %EBC was 0.67 (95% confidence interval [CI], 0.54-0.80; p = 0.01). A MVV >103.1% of EBC had 78.8% (95% CI, 61.1-91.0) sensitivity and 47.5% (95% CI, 31.5-63.9) specificity for predicting response to desmopressin. Among the patients with nocturnal polyuria according to definition 1, a higher percentage of subjects with nocturnal polyuria in 4 out of 5 or 5 out of 5 nights responded to desmopressin, compared with other patients. Patients presenting with nocturnal polyuria according to definition 3 in 5 out of 5 nights showed a 100% of response to desmopressin. At multivariate analysis, the only significant odds ratio (OR) to respond to desmopressin was that of patients with nocturnal polyuria according to definition 1 in >3 nights (OR = 7.1, 95% CI, 1.3-40.3). DISCUSSION AND CONCLUSIONS: The presence or absence of nocturnal polyuria-according to all three definitions-in at least one night was not effective in predicting the response to desmopressin. Predictors of desmopressin response were nocturnal polyuria in >3 out of 5 wet nights according to definition 1 and in 5 out of 5 wet nights according to definition 3.

Albumin: physiologic and clinical effects on lung function.

Fluid resuscitation is one of the most frequent and necessary practices in clinical medicine and is an integral part of the initial stabilization of critically ill, hypovolemic patients. Longstanding debate and conflicting evidence surround the use of both colloid and crystalloid fluid resuscitation in these patients. The basis of this debate is heavily rooted in the physiological understanding of Starling's forces. In this review, we aim to highlight the ongoing debate of albumin versus crystalloid resuscitation both broadly and as it relates to lung function, and will discuss the current state-of-the-art, starting from an historic perspective and progressing through a review of both physiologic and clinical evidence. Despite the biologic and physiologic plausibility of therapeutic benefit, the current evidence base does not support the routine use of albumin administration to improve patient survival or prevent respiratory dysfunction.

Looking at my body. Similarities and differences between anorexia nervosa patients and controls in body image visual processing.

BACKGROUND: Body image distortion is a core symptom of eating disorders. Functional magnetic resonance imaging (fMRI) studies on body image processing, described different patterns of neural response, mainly involving the inferior and superior parietal lobules, and the dorsolateral prefrontal cortex (DLPFC), with conflicting results. METHODS: The neural response to the view of their own body pictures (normal size and distorted) was evaluated in 18 female anorexia nervosa (AN) restricting type patients, and in 19 healthy female subjects (HC) using fMRI. Clinical assessment was performed by means of the structured clinical interview for DSM-IV and self-reported questionnaires. RESULTS: In response to the body image distortion, patients and controls showed an inverse pattern of activation, with the widest extent of activation in the oversize condition in AN, while in the undersize condition in HC. AN and HC showed a similar pattern of neural response to the view of their own body, with an increased activation in the extrastriate body area, superior and inferior parietal lobule and prefrontal areas, although the extent of activation in HC was more limited as compared with AN patients. Increased activity in AN patients, compared with HC, was observed in the DLPFC in response to the oversized body picture and a significant correlation was found in AN patients between DLPFC activation and eating disorder psychopathology. CONCLUSIONS: Our findings suggest the existence of a continuum from normalcy to pathology in neural response to body image, and confirm the clinical relevance of body image distortion in AN, reinforcing the key role of attentive, executive and self-evaluation networks in AN visual processing of own distorted body image.

Alternative normalization methods demonstrate widespread cortical hypometabolism in untreated de novo Parkinson's disease.

AIM: Previous positron emission tomography (PET) [18F]fluorodeoxyglucose ([18F]FDG) studies in Parkinson's disease (PD) demonstrated that moderate to late stage patients display widespread cortical hypometabolism, whereas early stage PD patients exhibit little or no cortical changes. However, recent studies suggested that conventional data normalization procedures may not always be valid, and demonstrated that alternative normalization strategies better allow detection of low magnitude changes. We hypothesized that these alternative normalization procedures would disclose more widespread metabolic alterations in de novo PD. METHODS: [18F]FDG PET scans of 26 untreated de novo PD patients (Hoehn & Yahr stage I-II) and 21 age-matched controls were compared using voxel-based analysis. Normalization was performed using gray matter (GM), white matter (WM) reference regions and Yakushev normalization. RESULTS: Compared to GM normalization, WM and Yakushev normalization procedures disclosed much larger cortical regions of relative hypometabolism in the PD group with extensive involvement of frontal and parieto-temporal-occipital cortices, and several subcortical structures. Furthermore, in the WM and Yakushev normalized analyses, stage II patients displayed more prominent cortical hypometabolism than did stage I patients. CONCLUSION: The use of alternative normalization procedures, other than GM, suggests that much more extensive cortical hypometabolism is present in untreated de novo PD patients than hitherto reported. The finding may have implications for our understanding of the basic pathophysiology of early-stage PD.

Functional neuroimaging in anorexia nervosa: a clinical approach.

AIMS: To provide a review of the available literature about the functional neuroimaging of anorexia nervosa, and to summarize the possible role of neurobiological factors in its pathogenesis. METHODS: A systematic review of the literature was performed using PubMed and Medline electronic database (1950-September 2009). Eligible studies were restricted to those involving the main parameters of cerebral activity and functional neuroimaging techniques. Findings of the reviewed studies have been grouped on a diagnostic subtype basis, and their comparison has been interpreted in terms of concordance. RESULTS: We found a high level of concordance among available studies with regard to the presence of frontal, parietal and cingulate functional disturbances in both anorexia nervosa restricting and binge/purging subtypes. Concordance among studies conducted regardless of the anorexia nervosa subtypes suggests an alteration in temporal and parietal functions and striatal metabolism. CONCLUSIONS: The most consistent alterations in anorexia nervosa cerebral activity seem to involve the dorsolateral prefrontal cortex, the inferior parietal lobule, the anterior cingulate cortex and the caudate nucleus. They may affect different neural systems such as the frontal visual system, the attention network, the arousal and emotional processing systems, the reward processing network, and the network for the body schema.

A new Minos vector for eye-specific expression of white+ marker in Ceratitis capitata and in distantly related dipteran species.

The genetic transformation of insects by transposable elements is based on the use of selectable genetic markers required to identify transgenic individuals. Conserved regulatory sequences can be used to develop single constructs capable of adequate expression of a marker, across a range of different species. We present evidence that the Drosophila GBS regulatory element (Glass-binding site), derived from the Rh1 rhodopsin gene, is able to drive in vivo eye-specific expression of a Ccwhite+ transgene in the Mediterranean fruitfly Ceratitis capitata. The Ceratitis lineage diverged from that of Drosophila approximately 120 Myr ago. As the GBS regulatory sequence seems to be partially conserved in the more distantly related dipteran species Anopheles gambiae (250 Myr), we propose that the GBS may be widely useful for driving eye-specific expression in a wide range of dipteran species.

Structure and expression of a novel gene family showing male germline specific expression in Drosophila melanogaster.

We report the characterization of two novel genes of Drosophila melanogaster, named mst36Fa and mst36Fb. They define a novel gene family, showing identical time and tissue-specificity limited to male germ cells where their transcription starts during meiotic prophase. These two genes encode for two slightly basic proteins highly homologous to each other and fairly rich in leucine and glutamic acid. Although strictly clustered, these genes utilize different promoter regions as revealed by examination of transgenic flies bearing mst36F-promoter-lacZ reporter constructs and by reverse transcription-polymerase chain reaction assays. Our data suggest that at least one gene (mst36Fa) of the cluster is under translational repression until spermiogenesis suggesting a putative role in the spermatides differentiation. The present study is aimed at the structural analysis of these genes.

[Detection of left ventricular endocardial border with tissue harmonic imaging]. / Vantaggi della seconda armonica tissutale nella identificazione del bordo endocardico ventricolare sinistro.

BACKGROUND: Ultrasonic wave propagation in human tissues is not linear. As a consequence, harmonic waves, whose frequency is a multiple (harmonic) of the emitted frequency, are generated. Tissue Harmonic Imaging (THI) processes only the second harmonic frequency in order to improve the signal-to-noise ratio of the received signal. The study was aimed at investigating the impact of THI on the detection of the Left Ventricular (LV) endocardial border. Attention was paid to determine which LV walls were analysed more clearly with THI rather than with conventional Fundamental Frequency Imaging (FFI). METHODS: We compared the FFI and the THI visualization of the 16 LV segments and of the 6 LV walls in 30 consecutive patients by scoring the images as bad, sufficient or good. The equipment used was a GE Vingmed System Five (Orten, Norway). RESULTS: Images were good in 85% of segments explored with THI, whereas FFI provided good images in 47% of segments (p<0.001). From the apical window, visualization of the apex, lateral wall and anterior wall significantly improved with THI; using the parasternal approach, imaging of posterior wall was definitely better with THI than with FFI. CONCLUSIONS: THI enhances both endocardial visualization and global image quality. Tech-nical development, however, increases the diagnostic possibilities of echocardiography but does not substitute the operator's experience.

Unilateral vesicoureteric reflux: Low prevalence of contralateral renal damage.

OBJECTIVE: We assessed the risk for the occurrence of renal damage in children with vesicoureteric reflux (VUR). STUDY DESIGN: We reviewed the records of 187 consecutive children, aged 3.8 +/- (SD) 2.8 years, with unilateral primary VUR diagnosed after urinary tract infection (UTI). Dimercaptosuccinic acid renal scintigraphy was performed 4 to 6 months after the last UTI. Three patterns of renal damage were identified: global reduction (GR) of renal radionuclide uptake (20% to 40% of relative uptake), focal defects (FD) in uptake, and shrunken (relative uptake <20%) kidney (SK). We assumed that in these subjects FD indicated postpyelonephritic damage and that GR indicated congenital renal damage. RESULTS: Scintigraphic renal damage of any type was present in 36.9% of the refluxing and in 3.2% of the nonrefluxing kidneys (odds ratio [OR], 17.6; 95% CI, 7.4 to 41.9). FD were present in 15.5% and 2.7% (OR, 6.7; CI, 2.5-17.6), GR in 19% and 0.5% (OR, 44.3; CI, 6.1 to 327.2), and SK in 6.9% and 0%, respectively. Patients with severe VUR showed a higher probability of renal damage than those with nonsevere VUR. CONCLUSIONS: In children with UTI and VUR, the refluxing kidney is most at risk of both congenital and acquired renal damage, and this risk increases with severity of reflux.

Hyperuricosuria in children: clinical presentation and natural history.

OBJECTIVE: Idiopathic hyperuricosuria (HU) was previously reported in only a limited number of children with hematuria. We aimed to outline the clinical presentation and natural history of HU not only in children with hematuria, but also in those with dysuria and/or recurrent abdominal/flank pain and a family history of urolithiasis. STUDY DESIGN: Retrospective analysis of data at diagnosis from 102 consecutive children with HU and outcome analysis of 26 of them who were followed >/=1 years (mean: 3.1) with no specific therapy. RESULTS: Sixty-one participants had HU and 41 had HU + hypercalciuria. Fifty-two patients had no hematuria among the presenting symptoms, more than one third had normal urinalysis at our first examination, one half had microcalculi (<3 mm in diameter) at renal sonography, and 12% had stones (4-18 mm). Thirty participants of the 39 with no hematuria at our first examination (77%) showed microcalculi or calculi at renal sonography. The patients with microcalculi were significantly older than were those without microcalculi. During the follow-up, 4 of 26 children never had hematuria and 8 had no hematuria during most of the follow-up period. Two patients who had a calculus at first visit and 3 who formed calculi 4 to 12 mm in diameter, after 1 to 3.5 years subsequently passed them in the urine. CONCLUSIONS: The lack of hematuria is not predictive of absence of urolithiasis. Therefore, it may be misleading to judge on the efficacy of a given therapy only based on disappearance of hematuria. HU and hypercalciuria have to be suspected in children with dysuria and those with recurrent abdominal/flank pain and familial history of urolithiasis, although they have no hematuria.

Idiopathic hypercalciuria and hyperuricosuria: family prevalence of nephrolithiasis.

We studied the prevalence of a history of nephrolithiasis in first- and second-degree relatives of 74 children with hypercalciuria (HC), 61 with hyperuricosuria (HU), and 41 with HC plus HU, and in a control population of 261 children with different diseases. Family history of nephrolithiasis was found in 69% of HC, 75% of HU, 78% of HC plus HU, and 22% of control patients. The prevalence was not different among HC, HU, and HC plus HU groups, but was significantly higher in each study group than the control group (P=0.0001). Body mass index >95th percentile was found in only 4.7% of the patients with HC or HC plus HU. Calculi (>3 mm in diameter) were present in 8.9% of the patients with a family history of nephrolithiasis and in 9.4% of those with no family history (P=0.85). Microcalculi (<3 mm in diameter) were found by sonography in 56.6% of the patients with and in 53.3% of those without a family history of nephrolithiasis (P=0.83). Children with HC and/or HU have a strong familial prevalence of nephrolithiasis. Obesity does not seem to affect the association of familial nephrolithiasis and hypercalciuria in children. The presence of nephrolithiasis in families of children with HC and/or HU is not associated with a higher rate of formation of calculi or microcalculi.

Enhanced detection of vesicoureteric reflux with isotopic cystography.

We compared the accuracy of isotope cystography (IC) and fluoroscopic cystourethrography (FC) in detecting vesicoureteric reflux (VUR) in children. FC and IC were performed in 124 children, 56 boys and 68 girls, aged 1 month to 9.2 years (mean 2.1 years), admitted consecutively for suspected VUR over a 10-month period. VUR was diagnosed by one or both studies in 51 of 124 (41%) patients. The two methods were concordant for the detection of VUR in 84% of kidney-ureter units and in 93% for the detection or exclusion of severe VUR. IC detected VUR more accurately than FC, both when all grades of VUR were considered together (P=0.00001) and when only severe reflux was considered (P=0.004). VUR was missed by FC in 23 of 51 (45%) subjects. Of those 23, 12 had severe VUR detected on one side at least by IC. VUR was missed by IC in 3 subjects. IC is significantly more accurate than FC in the initial diagnosis of VUR, even of severe grade. IC is the method of choice for the first diagnosis of VUR. Boys with VUR diagnosed by IC also need FC to investigate for posterior urethral valves.

High incidence of a generally small kidney and primary vesicoureteral reflux.

PURPOSE: We distinguished the scintigraphy pattern of congenital reflux nephropathy from that of acquired scarring in children with primary vesicoureteral reflux. MATERIALS AND METHODS: We retrospectively evaluated the frequency and pattern of renal scintigraphy abnormalities in 41 patients with prenatally detected primary vesicoureteral reflux and in 322 with a mean age plus or minus standard deviation of 3.6 + or - 1 years in whom primary reflux was detected after urinary tract infection. Dimercapto-succinic acid scintigraphy was performed 4 to 6 and 1 to 4 months after reflux was diagnosed and/or the infection was cured in patients with urinary tract infection and prenatal detection, respectively. RESULTS: We identified 3 patterns of renal damage, including overall decreased uptake of renal radionuclide that was 20% to 40% of relative uptake, focal defects in uptake and shrunken kidney with relative uptake less than 20%. Scintigraphy revealed renal damage in 12 prenatally detected cases of vesicoureteral reflux, including overall decreased uptake in 58% and shrunken kidney in 42%, and in 111 cases of reflux detected at urinary tract infection, including overall decreased uptake in 50%, uptake focal defects in 37% and shrunken kidney in 13%. In the urinary tract infection group overall decreased uptake was present in 25 of 90 boys and in 40 of 232 girls (p = 0.05). Of these children 15% of the girls had uptake focal defects and 17% had overall decreased uptake. Overall decreased uptake and uptake focal defects were significantly more common in kidney-ureter units with reflux grade 4 or greater than in those with grade 3 or less (p = 0. 00001 and 0.027, respectively). CONCLUSIONS: When assuming that overall decreased radionuclide uptake indicates congenital reflux nephropathy and uptake focal defects indicate postnatal acquired scarring, congenital reflux nephropathy appears to be an important cause of renal damage in children with primary vesicoureteral reflux even beyond the neonatal age and even in girls. This finding is of interest because postnatally acquired scarring may but congenital reflux nephropathy may not be prevented.

Cyclic voiding cystourethrography in the diagnosis of occult vesicoureteric reflux.

Cyclic voiding cystourethrography (CVC) enhances the detection of vesicoureteric reflux (VUR). We investigated whether more-severe VUR may be overlooked, and whether older children are at risk of having their VUR missed with the conventional single-cycle study. Three hundred and seventy patients, 168 boys and 202 girls aged 1 month to 16 years, consecutively admitted over 1 year for suspicion of VUR, underwent two complete cycles of filling and voiding CVC. One hundred and four subjects, 33 boys and 71 girls, were older than 3 years (mean age 5.7 years, range 3.2-16 years). Sixty-six refluxing ureters from 51 patients were identified in the first cycle and 61 refluxing ureters from 45 patients were identified only with the second cycle. Four instances of grade IV VUR in 4 patients and three of grade V VUR in 3 patients were overlooked completely in the first cycle. Seven episodes of VUR < or = grade III from 5 patients diagnosed in the first cycle were upgraded to > or = grade IV at the second cycle. The presence of VUR was identified only in the second cycle in 35 of 74 subjects aged < or = 3 years and in 10 of 22 aged > 3 years (not significant). Of the 10 children aged > 3 years, 2, who had diagnosis only at the second cycle, had > or = grade IV VUR. More-severe VUR may be overlooked or down-graded in a single-cycle study. Two-cycle CVC is also useful in children older than 3 years.