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.

Altered body water distribution in subjects with juvenile rheumatoid arthritis and its effects on the measurement of water compartments from bioelectric impedance.

OBJECTIVE: To assess the reliability of bioelectric impedance analysis (BIA) for predicting total body water (TBW) and extracellular water (ECW) in children affected by juvenile rheumatoid arthritis (JRA). SUBJECTS: Thirty-nine children affected by JRA and 23 healthy children of similar age (11.0 +/- 3.6, range 3.0-19.0 y) were recruited for the study. METHODS: TBW and ECW were measured by deuterium oxide and bromide dilution, respectively. Bioelectric impedance (Z) was measured at frequencies of 5, 50 and 100 kHz. The prediction of TBW and ECW from BIA was based on the impedance index (ZI = height2/Z, cm2/omega). RESULTS: TBW standardized per kg of body weight and ECW standardized per litre of TBW were significantly higher in JRA as compared to control patients (59.7 +/- 2.4 vs 57.7 +/- 2.7% and 44.5 +/- 4.6 vs 38.1 +/- 7.9%, with P < 0.005 and P < 0.0001, respectively). Moreover, intracellular water standardized per litre of TBW was significantly lower in JRA than in control subjects (55.5 +/- 4.6 vs 62.5 +/- 8.1, with P < 0.0001). In both controls and patients, the use of ZI at 5kHz offered the more accurate prediction of ECW. However, the use of ZI at 100 kHz did not offer a better prediction of TBW as compared to its value of 50 kHz. Control-generated formulae for predicting water compartments from BIA [TBW = 0.716 x ZI at 100 kHz-1.504, r = 0.934, s.e.e. = 2.2 l;:ECW = 0.430 x ZI5-3.652, r = 0.869(7) s.e.e. = 1.7 l] underestimated TBW and ECW in JRA patients. However, population-specific formulae [TBW (1) = 0.766 x ZI at 100 kHz-0.053, r = 0.939, s.e.e. = 2.8 l; ECW (l) = 0.399 x ZI at 5 kHz-0.283, r = 0.886, s.e.e. = 1.7 l] allowed an accurate prediction of TBW and ECW in JRA patients, taking into account their altered body water distribution. CONCLUSIONS: Altered water distribution impedes the use of formulae developed on healthy children to predict TBW and ECW from BIA and JRA patients. It is hypothesized that chronic inflammation and subclinical malnutrition may be responsible for the altered body water distribution of JRA patients. Traditional body composition models may require adjustments for use in JRA children due to their altered body hydration and water distribution.

Delayed pubertal growth spurt and normal adult height attainment in boys receiving long-term alternate-day prednisone therapy.

Statural growth to age > or = 20 years was studied in 10 boys with glomerulonephritis who received alternate-day prednisone (mean 1.2 mg/kg) for at least 2 consecutive years during pubertal age. Peak growth velocity was delayed after age 15 years in six patients and it was less than 7 cm/year in five. However, after age 16, growth velocity was significantly (p = 0.02) higher than expected and allowed patients to ultimately reach their genetic height potential.

Renal calyceal microlithiasis: clinical presentation may precede sonographic evidence.

Calyceal microlithiasis (CM) is characterized by the sonographic finding of hyperechogenic spots less than 3 mm in diameter in renal calyces, and it may be the first step in calculus formation. From January 1992 to January 1998, we have observed 216 children with CM. The present report deals with 34 of them in whom renal sonography was negative at first observation and the diagnosis of CM was made only on repeated sonographic examinations. The presenting symptoms were recurrent abdominal pain, dysuria, and hematuria occurring alone or in combination. Half of the patients had hypercalciuria. A history of urolithiasis in at least one first- or second-degree relative was present in 85% of patients. Renal sonography was repeated after 6-22 months (mean 11) and showed unilateral CM in 16 subjects and bilateral in 18. The finding of CM may be preceded by a period of time when symptoms and/or signs are present while microcalculi are not yet detectable. Repeated ultrasound examinations may be needed not only in patients with hypercalciuria but also in those with recurrent abdominal pain, dysuria, and/or hematuria not associated with hypercalciuria.

Bone mineral content in nephrotic children on long-term, alternate-day prednisone therapy.

Bone mineral content (BMC) was measured by single-photon absorptiometry in 24 children with steroid-dependent, minimal-lesion nephrotic syndrome after 1 to 6.3 years of alternate-day prednisone therapy and in a sex- and age-matched control group. Bone mineral content was -0.002 +/- 1.2 standard deviation scores in patients and 0.3 +/- 1.4 in controls (t = 1.17; P = 0.25). No significant relation was found between BMC in patients and the amount of prednisone taken or the duration of therapy. Alternate-day prednisone therapy at doses usually needed to keep children with steroid-dependent nephrotic syndrome under control does not significantly affect BMC.

[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.

[One-year treatment of 43 chronic hemodialysis patients with recombinant human erythropoietin]. / Traitement pendant un an de 43 malades hémodialysés chroniques par l'érythropoïétine recombinante humaine.

Twenty men and 23 women aged from 18 to 65 years, who had been under maintenance haemodialysis for 2 to 16 years and whose haematocrit had been below 30 percent for at least 3 months received recombinant human erythropoietin intravenously at the end of each session for one year. Anaemia was corrected in all patients, the delay in response to each dosage variation being about 4 weeks. The necessary maintenance dosage ranged from 96 to 240 u/kg/week. The number of leucocytes increased significantly until the 4th month, from 5880 +/- 1760 to 6600 +/- 1920 per cubic mm (P less than 0.01). During treatment, pre-dialysis blood creatinine concentrations and potassium and phosphate levels rose, while blood calcium levels fell significantly from 2.45 +/- 0.16 to 2.36 +/- 0.19 mmol/l (P less than 0.01). A nonsignificant increase in systolic and diastolic pressures was also observed, from 129 +/- 16 to 134 +/- 18 mmHg (P = 0.06) and from 75 +/- 9 to 78 +/- 10 mmHg (P = 0.07) respectively. Eight patients (18 percent) required antihypertensive drugs or a higher dose of those previously prescribed. There were 7 cases of vascular thrombosis on pre-existing stenosis, and the dosage of heparin during dialysis had to be increased in most patients. This study confirms that erythropoietin plays a major role in the genesis of the anaemia associated with renal failure. The absence of severe complications in this series was probably due to the criteria of inclusion in the study.

[Glomerulonephritis caused by a shunt: description of a case]. / Glomerulonefrite da shunt: descrizione di un caso.

The authors report a case of shunt-nephritis due to bacteremia from Stafilococcus albus. Kidney biopsy, comprehensive of IF study allowed to assess the diagnosis of a disease from immunocomplexes. The Authors stress the importance of a close follow-up of patients who carry liquoral shunt for an early recognition of symptoms of glomerulopathy.

[Must renal biopsy be still performed in "lipoid nephrosis"? (author's transl)]. / Esiste ancora indicazione all biopsia renal nella "nefrosi lipoidae"?

In 52 out of 272 children with one of the following diseases: nephrotic or nephritic syndrome, persistent humaturia and/or proteinuria, renal biopsy was performed on the basis of commonly accepted indications. 18 biopsies were from patients with a clinical picture of lipoid nephrosis and clinical course of "non responders" or "frequent relapsers" types. All of them showed the histologic pattern of minimal changes and had a value of Y index according to ISKCD greater than 0,85. Moreover all patients with minimal changes nephrotic syndrome had a Y index greater than 0.85. If these observations will be confirmed renal biopsy would not later be indicated in children with "lipoid nephrosis".

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.