Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance.

OBJECTIVE: Lipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations. DESIGN: We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obese women (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants). RESULTS: Serum NGAL concentration was significantly associated with fasting triglycerides and LPS-binding protein in patients with type 2 diabetes. In obese subjects, the intake of saturated fatty acids was the factor that best explained the variance of NGAL changes after weight loss (contributing independently to 14% of NGAL variance). In fact, weight loss significantly changed the circadian rhythm of NGAL. The acute increase in circulating NGAL after fat overload was significantly associated with fasting insulin (r=0.52, P<0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.36, P=0.02) and post-load triglyceride concentrations (r=0.38, P=0.018). LPS-induced NGAL secretion from adipose tissue explants did not change significantly, but LPS led to a significant increase in NGAL concentration in the whole blood obtained from patients with type 2 diabetes. CONCLUSION: Metabolic endotoxemia and saturated fat might contribute to circulating NGAL concentration in patients with insulin resistance.

Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion.

AIMS/HYPOTHESIS: We tested the hypothesis that the reversibility of insulin resistance and diabetes observed after biliopancreatic diversion (BPD) is related to changes in circadian rhythms of gastrointestinal hormones. METHODS: Ten morbidly obese participants, five with normal glucose tolerance (NGT) and five with type 2 diabetes, were studied before and within 2 weeks after BPD. Within-day variations in glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1) levels were assessed using a single cosinor model. Insulin sensitivity was assessed by euglycaemic-hyperinsulinaemic clamp. RESULTS: Basal GLP1 relative amplitude (amplitude/mesor x 100) was 25.82-4.06% in NGT; it increased to 41.38-4.32% after BPD but was unchanged in diabetic patients. GLP1 and GIP mesor were shifted in time after surgery in diabetic patients but not in NGT participants. After BPD, the GLP1 AUC significantly increased from 775 +/- 94 to 846 +/- 161 pmol l(-1) min in NGT, whereas GIP AUC decreased significantly from 1,373 +/- 565 to 513 +/- 186 pmol l(-1) min in diabetic patients. Two-way ANOVA showed a strong influence of BPD on both GIP (p = 0.010) and GLP1 AUCs (p = 0.033), which was potentiated by the presence of diabetes, particularly for GIP (BPD x diabetes, p = 0.003). Insulin sensitivity was markedly improved (p < 0.01) in NGT (from 9.14 +/- 3.63 to 36.04 +/- 8.55 micromol [kg fat-free mass](-1) min(-1)) and diabetic patients (from 9.49 +/- 3.56 to 38.57 +/- 4.62 micromol [kg fat-free mass](-1) min(-1)). CONCLUSIONS/INTERPRETATION: An incretin circadian rhythm was shown for the first time in morbid obesity. The effect of BPD on the 24 h pattern of incretin differed between NGT and diabetic patients. GLP1 secretion impairment was reversed in NGT and could not be overcome by surgery in diabetes. On the other hand, GIP secretion was blunted after the operation only in diabetic patients, suggesting a role in insulin resistance and diabetes.

The role of P300 in the recovery of post-stroke global aphasia.

Seventeen right-handed patients suffering from global aphasia caused by a recent stroke in the left-hemisphere were studied. Passive P300 auditory event related potential paradigm was applied every months for 6 months. Aachen subtests were used for evaluating comprehension. Only a minority of the patients displayed the P300 at the baseline. Those patients had the best outcome at the Aachen comprehension subtest. Latency and amplitude changed over time in an unpredictable way. The number of patients presenting with the P300 also fluctuated, since some patients could regain the potential, whereas some other patients could lose that from month to month. Passive P300 is a monitor of recovery following global aphasia. A single passive P300 recording is useful for prognostic purposes. Repairing mechanisms in the first 6 months have a non-linear trend.

The aftermath of rehabilitation for patients with severe stroke.

OBJECTIVE: The study evaluates the aftermath of stroke in patients with very severe disability after their first ever stroke and dismissed after rehabilitation. MATERIALS AND METHODS: Sixty-nine inpatients were studied, who were highly disabled at discharge with a Functional Independence Measure (FIM) score in the range of 18-39. Their rehabilitation program had lasted 60 days. The degree of functional independence was measured by means of the FIM at the beginning of treatment, at discharge and at follow-up. The data collected were examined by using parametric and distribution-free statistical methods. The role of age in the process of recovery was also evaluated. RESULTS: All patients were discharged home after 2 months. At 6 month follow-up, 15 patients (21.7%) were lost, 27 (39.1%) had died and 27 (39.1%) lived at home. Among stroke survivors a clear trend toward an improvement was detected during the 6 months observation period. Indeed, the third quartile changed from 33 to 63 and a patient approached to independence (FIM 87). None underwent a rehabilitation program at home beside the relatives' assistance. CONCLUSIONS: Highly disabled stroke patients are probably to undergo unfavourable outcome but unexpected recovery cannot be ruled-out on the basis of cut-off parameters measured after the acute phase of stroke. Multivariate statistical methods can identify factors which can interfere with functional recovery but are error-prone in setting individual prognosis. Moreover the recovery process may develop in a long period of time. Taking into consideration the spontaneous recovery observed during the follow-up period after the dismissal from rehabilitation ward, a suitable rehabilitation at home might be fruitful in these patients, who should not be considered as "lost".

The effects of atrial fibrillation on functional recovery in post-stroke patients.

PURPOSE: This study evaluates the negative effects of atrial fibrillation (AF) on after stroke recovery and its relationship with age and other concomitant diseases. METHOD: One hundred and ninety-nine consecutive inpatients, after their first stroke, were enrolled and entered a rehabilitation program lasting 60 days. The mean interval since the stroke was 19 days. The disability, both at admission and at discharge, was assessed by Functional Independence Measure (FIM). Atrial fibrillation was diagnosed at admission on the basis of electrocardiographic recordings. Gender, age, blood pressure and blood sugar level were also taken into account. RESULTS: Stroke patients suffering from AF, when compared to those lacking AF, have higher disability at admission as well as at discharge and had a lesser gain in functional recovery. No statistical difference of the AF occurrence was found between male and female patients. The negative correlation between age and functional gain was found only in AF patients. There was also a significant association between AF and hypertension, but not between AF and diabetes. At the beginning and at the end of the study, the median FIM scores of all the patients with AF were quite similar irrespective of manifesting hypertension, diabetes or neither of these two. CONCLUSIONS: The presence of AF has a negative prognostic value on post stroke outcome, particularly in the elderly patients. The pattern of recovery of stroke subjects having AF is not influenced by concomitant diseases like hypertension or diabetes.

Chest conduction properties and ECG equalization.

In common practice of detecting and recording biomedical signals, it is often implicitly assumed that the propagation, through the whole circuit human body-electrodes recording devices, is frequency and voltage independent. As a consequence, clinicians are not aware that recorded signals do not correspond faithfully to the original electrical activity of organs under investigation. We have studied the transmission of electrical signals in human body at various voltages and frequencies to understand if and to which extent the most diffused stimulating and recording techniques used in medicine are affected by global body conduction properties. Our results show that, in order to obtain a more faithful detection of electrical activity produced or evoked by human organs (e.g. EGG, electromyography, etc.), it is convenient to 'equalize'' recorded signals. To this purpose, two equalization techniques are proposed, based, respectively, on a simple hardware filtering during acquisition, or FFT post-processing of the acquired signals. As an application, we have studied the transmission of electrical signal in human chest and have compared equalized high frequency ECG signals with raw (original) recordings.

On the prognosis of outcome after stroke.

OBJECTIVES: The study was aimed at improving the accuracy of prognosis for recovery of function in patients suffering a first stroke. MATERIALS AND METHODS: Two-hundred and forty-eight patients were enrolled. The mean interval since the stroke was 23 days. Patients entered a rehabilitation program lasting 60 days. The predictive value of 12 factors were analysed, namely motor, cognitive and sphincter subitems of Functional Independence Measure at admission (FIM-a), age, sex, education, body mass index (BMI), depression, neglect, aphasia, ideomotor and constructive apraxia. FIM score at discharge was the dependent variable. RESULTS: A multiple regression revealed that only age, cognitive and sphincter subitems of FIM-a, neglect and ideomotor apraxia were significantly associated with outcome. Moreover, these factors accounted for only 72% of the variance in outcome scores. A decision of unfavourable prognosis on the basis of a FIM-a value lower than 40 was incorrect in 2.8% of the patients in this study and in 8.2% of those having a FIM score lower than 40. CONCLUSIONS: The use of statistical methods to examine the outcome after stroke is useful for expressing probability on a group basis but is unsuitable for determining the prognosis of individual patients. Such data should not be used for fiscal management. A significant minority of patients presenting with a FIM lower than 40 can regain a useful measure of independence. The errors in prognosis based upon available methods, although small, have unacceptable effects in human terms if they lead to the clinical decisions which deny patients rehabilitation. All of the patients should therefore be admitted for rehabilitation after their first stroke. Severe comorbidity requires special attention.

Effects of propionyl-L-carnitine on peripheral arterial obliterative disease of the lower limbs: a double-blind clinical trial.

The authors evaluated the efficacy of propionyl-l-carnitine, a drug able to reduce peripheral resistance and protect the cells against oxidative stress damage, in patients affected by peripheral arterial obliterative disease at class II of Fontaine. The study was performed on 22 patients according to a double-blind, randomized design in parallel with placebo. The drug was administered at a dosage of 1 g three times a day orally for 90 days. At recruitment and at the end of the study all patients underwent physical examination, treadmill test, doppler C.W. of the lower limbs, ankle/brachial index, dosage of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), hematocrit, hematic filtration, and viscosity. In the group treated with propionyl-l-carnitine a statistically significant increase of claudication distance, blood flow velocity, PAI-1 activity and red blood cell deformity was observed. These data suggest the usefulness of propionyl-l-carnitine in the treatment of patients affected by peripheral arterial obliterative disease.

Dyscalculia in the early stages of Alzheimer's disease.

OBJECTIVE: To study mathematical deficits in the early stages of Alzheimer's disease (AD). METHODS: Sixty-eight patients with mild AD and 242 normal controls (NC) received a standardized battery (EC 301-R) assessing number processing and calculation abilities. AD patients also received testing for language, memory, visuo-spatial and executive-attentional domains. RESULTS: Sixty-four AD patients (94.1%) showed impaired performances on the EC 301-R. Mathematical deficits were evident both on calculation and number processing skills. Performance on the single tasks was related to attentional-executive resources and to impaired number representations. Heterogeneous patterns of preserved/impaired mathematical abilities were also observed in single cases. CONCLUSION: Dyscalculia is an early sign of AD. It should be included among the reliable clinical hallmarks for the diagnosis of AD. Identification of dyscalculic symptoms in these patients requires composite assessment procedure.

Brainstem involvement in obsessive-compulsive disorder.

We investigated the possible involvement of the brainstem in the pathology of obsessive-compulsive disorder. Brainstem auditory evoked potentials (BAEPs) were collected from a population of neurotics (100 patients), including a group of 50 subjects suffering from obsessive-compulsive disorder (OCD) and the rest having generalized anxiety disorder. Twenty-five, age- and sex-matched, healthy volunteers served as controls. BAEPs were recorded by standard techniques as recommended by the AEEGS Clinical Evoked Potentials Guidelines. A one-way analysis of variance and the Fisher least-significant difference test were used for statistical analysis of the data. After stimulation of the right ear, a significant increase of wave I-V interpeak latency was found in the two groups of patients as compared with that of controls. Moreover OCD patients had a significantly reduced amplitude of wave III when compared to that of the control group. Our electrophysiological data suggest a possible involvement of brainstem in OCD pathogenesis. We discuss our findings in relation to biochemical, anatomical and physiological alterations described in the literature for serotonin-dependent systems.

Hippocampus and parahippocampal gyrus linear measurements based on magnetic resonance in Alzheimer's disease.

MRI-based linear measurements of the hippocampus and parahippocampal gyrus complex (HPC) discriminated 39 subjects with probable Alzheimer's disease, from 15 patients with other dementias and 33 miscellaneous controls without evidence of dementia. The best discriminating parameter was the left height of the HPC at the level of the mammillary bodies, with a sensitivity of 79.49% and a specificity of 68.75%. The diagnostic value of these results is discussed considering the volumetric data found in the current literature.

EEG spectral analysis in Alzheimer's disease and different degenerative dementias.

The EEG was recorded in 25 patients with Alzheimer's disease (AD), 25 patients with non-Alzheimer degenerative dementias (NAD), matched for age and severity of dementia and 50 age- and sex-matched normal subjects. The recordings were made with the subjects at rest with eyes closed (REC) and opened (REO). The data was subjected to spectral analysis and the power was computed in five contiguous 5.5 Hz bandwidths in the range 1-28.5 Hz. The present study confirms the consistent prevalence of a spectrum characterised by the lack of a dominant activity in the 6.5-12 Hz band with high power in 1-6.5 Hz band in AD. Moreover quantitative spectral parameters discriminate not only AD from the other groups, but also NAD from age matched normal subjects.

Depression after stroke: an investigation through catamnesis.

BACKGROUND: In the early stage of stroke, depression appears to be linked to certain brain areas. The study evaluated the importance of the side of the lesion in depressed patients 3 years after their first stroke. METHOD: Patients who had suffered a stroke and been discharged after rehabilitation were identified by hospital records. We interviewed 180 patients at home. Demographic as well as socioeconomic data were collected. The North-western University Disability Scale, the Beck Depression Inventory (BDI), the Relatives' Stress Scale, and the Social Dysfunction Rating Scale were applied. The diagnosis was confirmed for each patient by a clinical assessment according to the ICD-10 criteria. Patients with previous psychiatric treatment, comprehension problems, or severe hemi-inattention were excluded. RESULTS: By using a score of 14 on the BDI as a cutoff, 62 patients (34%) proved to be affected by depressive disorders. Clinical records showed that the location of the lesion was in the right hemisphere for 37 patients and in the left hemisphere for 25 patients. Statistical analysis of the mean scores obtained in this subgroup of depressed patients showed (1) no significant relation between depression and the hemispheric location of the lesion or between depression and level of education; (2) relation between BDI score and social activities; and (3) stress on the relatives that was mainly dependent on both the disability of the patients and their loss of social activities, whereas depression played a minor role. CONCLUSION: A high percentage of patients have depressive disorders 3 years or more after the stroke, independent of the side. Such mood disorders worsen the relationship between the disabled patients and their relatives and worsen leisure independent of the affected hemisphere.

EEG power spectrum typical of vascular dementia in a subgroup of Alzheimer patients.

A statistical comparative study was carried out between two subgroups of patients with dementia, i.e. 22 with Alzheimer's dementia (AD, 44% of the entire Alzheimer group examined) and 36 with vascular dementia (VaD, 97% of the entire vascular group). The selection of the two subgroups was based on a similar EEG spectral profile in the rest eyes closed condition: a great increase in low frequency powers and a dominant activity in the 6.5-12 Hz band. The aim was to identify any possible difference between the two groups analysing the spectral descriptors, of the two conditions eyes closed and open, the demographic figures and the mental deterioration scores. The results are as follows: (i) the spectral profiles and their numerical descriptors of the AD subgroup patients are not distinguishable from the same parametric figures of the VaD patients; (ii) the spectral analysis becomes useful in differentiating the two types of dementia when a dynamic EEG is processed, i.e. the power ratio of recordings during eyes closed and open; (iii) a more severe mental deterioration, especially in attention and spatial and temporal orientation was found in the AD group as compared to the VaD. The findings are explained in the light of the changes in neural mechanisms which underlie both the alpha and slow rhythms.

EEG spectral analysis in vascular and Alzheimer dementia.

The role of EEG spectral analysis in the diagnosis of syndromes of dementia is still disputed. Since there have been few studies dealing with the profile of power spectra, the present investigation has focused on this aspect, constructing power spectra taken from 16 derivations and calculated by averaging twenty 2 sec epochs, using a serial array of frequencies from 1 to 32 Hz. The spectral analysis of the EEG, recorded under awake resting eyes closed (REC) and open (REO) conditions, was performed in 50 patients with Alzheimer's disease (AD), 37 with vascular dementia (VaD) and 36 elderly controls. Three spectral profiles were found under REC: (i) type A, showing a dominant 6.5-12 Hz peak (44% AD, 97.3% VaD), although lower than in controls; (ii) type B, lacking a dominant peak in the 6.5-12 Hz band, but characterised by high power in 1-6.5 Hz band (44% AD, 2.7% VaD); (iii) type C, corresponding to a flat, low voltage, spectrum (12% AD). Unlike controls, demented patients showed an increased REO/REC power ratio in the 6.5-12 Hz band, especially in those with type B spectra. AD patients with type B spectra had an earlier age of disease onset.

Levosulpiride: a review of its clinical use in psychiatry.

Levosulpiride is the (-)-enantiomer of sulpiride. It has shown greater central antidopaminergic activity, antiemetic and antidyspeptic effects and lower acute toxicity than both the racemic and dextro forms. Several clinical studies indicate that levosulpiride has therapeutic efficacy in depressive and somatoform disorders, as well as in schizophrenic patients with predominant negative features. All controlled studies report a low frequency of extrapyramidal and autonomic side-effects. The increase of plasma prolactin concentration is the major drawback of the use of the drug, but its frequency may be reduced by low dosage.

An electrophysiological study in obsessional compulsive disorders.

Recent anatomoclinical and neuroimaging studies have suggested a possible relation between obsessional compulsive disorders (OCD) and some brain damage, such as frontolenticular lesions, basal ganglia cavitations and local glucose metabolism impairment. A poor frontocaudal regulation of the left hemisphere and an autonomic nervous system dysfunction in OCD patients have been supposed. To absess these morphofunctional abnormalities, an electrophysiological approach has been performed in 100 consecutive neurotic patients, screened with various neuropsychological tests and divided in two groups, 50 with OCD and 50 with anxious neurosis (ANX). Patients were submitted to EEG spectral analysis and BAEP studies and comparated with 25 age-matched normal controls. The mean alpha power in occipital regions was significantly higher in OCD patients and reduced in ANX patients. A significant reduction of the beta activity was recorded in frontal regions in both patient groups as compared to controls. A slight (p < 0.11) increase in I-V interpeak latency (IPL) vs. control group was observed in BAEP from left ear. A significant increase of the same IPL in OCD vs. controls (p < 0.025) was observed in BAEP from right ear. A slight n.s. reduction in III wave amplitude in OCD patients was observed in BAEP from left ear, whereas a highly significant reduction in the same wave amplitude from BAEP from right ear was observed in OCD patients. The above findings cold be account for both a frontotemporal and brainstem dysfunction with a probable involvement of serotoninergic central pathways, with a significant impairment of pontine segment in ANX patients and of mesencephalic region in OCD patients.

S.P.E.C.T., E.E.G. and M.R.I. investigations in complex partial epilepsy.

We present SPECT, electroencephalography (EEG) and magnetic resonance imaging (MRI) data of a homogeneous group of 12 young adults with rare focal seizures and a good response to carbamazepine. Our data suggest that the alterations of the rCBF are independent of severity and duration of the epilepsy and of the frequency of seizures. Based on our experimental data, it may be suggested that complex partial epilepsy is a good biological model to investigate the neurogenic control of cerebral flow and metabolism.

EEG recordings in the course of recovery from stroke.

BACKGROUND AND PURPOSE: This study was designed to assess the value of quantified electroencephalography (EEG) in the follow-up of stroke and its possible correlation with other measures of recovery. METHODS: EEGs were recorded over a period of 6 months in 34 patients with ischemic stroke in the middle cerebral artery territory who underwent spectral analysis. Two groups were formed: (1) 28 patients with a Barthel Index score of less than 60 at admission and (2) 6 patients with a Barthel score of over 60 and therefore with a much better prognosis. Ten recordings were made in each patient in the first group and at least three in the second group. Motor functions and activities of daily living (ADL) were assessed three times, on admission to the study and after 3 and 6 months. RESULTS: Quantified EEG was significantly abnormal in the affected hemisphere of the first group. Side and site were not relevant. Longitudinal recordings showed a significant improvement of the power spectrum in the first 3 months. Alpha mean weighted frequency of the injured hemisphere was always slower than that of the contralateral side. All patients improved in motor performance and ADL, with the greatest gain in the first 3 months. However, no correlation between quantified EEG and clinical testing was found. By looking at individual profiles, a frequent and unpredictable instability was seen in the "unaffected" hemisphere. In those who made the best recovery, the EEG spectrum became more symmetrical over the left and right hemispheres, an aspect that continued beyond the point of a good motor and ADL recovery. CONCLUSIONS: Quantified EEG undergoes early and subtle changes in the follow-up of stroke that can outlast clinical recovery. Routine evaluation for prognosis is not recommended because motor and ADL scales provide earlier and more accurate indicators. In contrast, quantified EEG can be useful for individual patients undergoing rehabilitation to monitor mechanisms of local repair and also to detect changes in the so-called normal hemisphere. It may reveal focal abnormalities that are undetected by coarse clinical evaluation and that call for appropriate neuropsychological testing.

Somatosensory evoked potentials in non-insulin-dependent diabetics with different degrees of neuropathy.

Changes in median nerve somatosensory evoked potential (SEP) in diabetic patients have amply been reported. However the relationships between the diabetic polyneuropathy and the abnormalities of SEPs are still a matter of discussion. To elucidate these relationships, we have studied SEPs in 38 non-insulin-dependent diabetics with mild or severe degree of peripheral neuropathy. Our principal findings are as follows. (i) The wrist-Erb point (EP) conduction velocity (WECV) and the EP-N13 interpeak latency are significantly altered in diabetics. The N11-N13, N13-N20 and N13-P22, interpeak latencies are within the normal range. (ii) The WECV is more reduced in patients with severe neuropathy than in those with mild neuropathy, whereas the degrees of neuropathy have no influence on the alterations of EP-N13 interpeak latency. (iii) No significant correlation is found between the WECV and the EP-N13 interpeak latency. (iv) The WE conduction velocity was significantly correlated with both motor and sensory peripheral nerve conduction velocities. On the contrary, no correlation is found between these latter peripheral parameters and the EP-N13 interpeak latency. These findings indicate that the alteration in the tract from brachial plexus to the posterior column could not be a parallel process of distal neuropathy of non-insulin-dependent diabetic patients.