Outer retina dysfunction and choriocapillaris impairment in type 1 diabetes.

To study the outer retina morpho-functional characteristics and the choriocapillaris (CC) features in type 1 diabetic (T1D) patients, with and without signs of diabetic retinopathy (NPDR and NoDR). Twenty-five NPDR and 18 NoDR eyes were imaged by Optical Coherence Tomography Angiography. Ellipsoid zone (EZ) "normalized" reflectivity and CC perfusion density parameters, as flow deficits number (FDn), flow deficit average area (FDa) and flow deficit percentage (FD%), were analysed. Multifocal electroretinogram (mfERG) response amplitude densities (RADs) were measured. Mean EZ "normalized" reflectivity, CC FDn and FD% values, were similar (p > 0.05) in both groups, FDa was significant greater (p > 0.05) in NPDR compared with NoDR eyes. MfERG-RADs were similar in both groups. NPDR eyes showed a significant (p < 0.05) linear correlation between RADs and both, CC FDa and FD%. The EZ "normalized" reflectivity was negatively correlated with CC FD% in NoDR eyes. In NPDR T1D eyes a significant relationship between abnormal outer retina functional responses and CC impairment was observed, while in NoDR eyes the photoreceptor reflectivity was correlated to CC abnormalities. The outer retina dysfunction in NPDR correlated to CC drop-out let hypothesize that the outer retinal elements are functionally impaired in proportion to the CC vascular supply deficit.

Brain activation induced by psychological stress in patients with schizophrenia.

Environmental influences are critical for the expression of genes putatively related to the behavioral and cognitive phenotypes of schizophrenia. Among such factors, psychosocial stress has been proposed to play a major role in the expression of symptoms. However, it is unsettled how stress interacts with pathophysiological pathways to produce the disease. We studied 21 patients with schizophrenia and 21 healthy controls aged 18 to 50years with 3T-fMRI, in which a period of 6min of resting state acquisition was followed by a block design, with three blocks of 1-min control-task, 1-min stress-task and 1-min rest after-task. Self-report of stress and PANSS were measured. Limbic structures were activated in schizophrenia patients by simple tasks and remained active during, and shortly after stress. In controls, stress-related brain activation was more time-focused, and restricted to the stressful task itself. Negative symptom severity was inversely related to activation of anterior cingulum and orbitofrontal cortex. Results might represent the neurobiological aspect of hyper-reactivity to normal stressful situations previously described in schizophrenia, thus providing evidence on the involvement of limbic areas in the response to stress in schizophrenia. Patients present a pattern of persistent limbic activation probably contributing to hypervigilance and subsequent psychotic thought distortions.

A hybrid mathematical model for self-organizing cell migration in the zebrafish lateral line.

In this paper we propose a discrete in continuous mathematical model for the morphogenesis of the posterior lateral line system in zebrafish. Our model follows closely the results obtained in recent biological experiments. We rely on a hybrid description: discrete for the cellular level and continuous for the molecular level. We prove the existence of steady solutions consistent with the formation of particular biological structure, the neuromasts. Dynamical numerical simulations are performed to show the behavior of the model and its qualitative and quantitative accuracy to describe the evolution of the cell aggregate.

Sleep quality following hematopoietic stem cell transplantation: longitudinal trajectories and biobehavioral correlates.

The present study examined changes in sleep quality following hematopoietic stem cell transplantation (HSCT) and investigated associations with biobehavioral factors. Individuals undergoing HSCT for hematologic malignancies (N=228) completed measures of sleep quality and psychological symptoms pre-transplant and 1, 3, 6 and 12 months post transplant. Circulating inflammatory cytokines (IL-6, TNF-α) were also assessed. Sleep quality was poorest at 1 month post transplant, improving and remaining relatively stable after 3 months post transplant. However, approximately half of participants continued to experience significant sleep disturbance at 6 and 12 months post transplant. Mixed-effects linear regression models indicated that depression and anxiety were associated with poorer sleep quality, while psychological well-being was associated with better sleep. Higher circulating levels of IL-6 were also linked with poorer sleep. Subject-level fixed effects models demonstrated that among individual participants, changes in depression, anxiety and psychological well-being were associated with corresponding changes in sleep after covarying for the effects of time since transplant. Sleep disturbance was most severe when depression and anxiety were greatest and psychological well-being was lowest. Findings indicate that sleep disturbance is a persistent problem during the year following HSCT. Patients experiencing depression or anxiety and those with elevated inflammation may be at particular risk for poor sleep.

Subcutaneous emphysema, pneumomediastinum, pneumoretroperitoneum, and pneumoscrotum: unusual complications of acute perforated diverticulitis.

Pneumomediastinum, and subcutaneous emphysema usually result from spontaneous alveolar wall rupture and, far less commonly, from disruption of the upper airways or gastrointestinal tract. Subcutaneous neck emphysema, pneumomediastinum, and retropneumoperitoneum caused by nontraumatic perforations of the colon have been infrequently reported. The main symptoms of spontaneous subcutaneous emphysema are swelling and crepitus over the involved site; further clinical findings in case of subcutaneous cervical and mediastinal emphysema can be neck and chest pain and dyspnea. Radiological imaging plays an important role to achieve the correct diagnosis and extension of the disease. We present a quite rare case of spontaneous subcutaneous cervical emphysema, pneumomediastinum, and pneumoretroperitoneum due to perforation of an occult sigmoid diverticulum. Abdomen ultrasound, chest X-rays, and computer tomography (CT) were performed to evaluate the free gas extension and to identify potential sources of extravasating gas. Radiological diagnosis was confirmed by the subsequent surgical exploration.

An unusual case of bilateral granulomatous mastitis.

Idiopathic granulomatous mastitis (IGM) is an uncommon benign disorder of the breast. At clinical examination, IGM is characterized by an inflammatory process of the breast, usually unilateral. Possible clinical findings are palpable mass with erythematous skin, pain, sterile abscesses, fistula and nipple retraction. Mammography and ultrasound findings are not specific for IGM. Magnetic resonance imaging (MRI) is a useful tool for the differential diagnosis; it is also necessary to delineate the exact extension of the disease and to plan the correct treatment. Final diagnosis is histological. We described an unusual case of IGM with bilateral involvement in a patient with history of pacemaker implantation and IGM typical clinical symptoms. Mammography, ultrasound, and MRI examinations were performed to identify the inflammatory disorder and to plan the correct therapy. Imaging features were correlated with final histological diagnosis of IGM.

Adjusting to life after treatment: distress and quality of life following treatment for breast cancer.

Clinical and anecdotal findings suggest that the completion of cancer treatment may be marked by heightened distress and disrupted adjustment. The present study examined psychological adjustment during the 3 months following treatment among 89 women with stages 0-III breast cancer. Participants completed measures of depression, cancer-related anxiety, cancer concerns, and quality of life at three time points: during treatment, 3 weeks following the end of treatment, and 3 months post-treatment. Post-treatment scores were suggestive of good psychological adjustment among the majority of women. Moreover, distress did not increase following treatment; longitudinal analyses showed no significant changes in depression or recurrence worry, while intrusive thoughts decreased, and quality of life improved. Younger age predicted greater distress across measures. A history of depression or anxiety predicted greater depressive symptomatology, while more extensive treatment predicted greater cancer-related anxiety. Despite the lack of distress endorsed on general depression and anxiety indices, participants reported moderate distress associated with cancer-related concerns, including physical problems, fear of cancer recurrence, and resuming normal life. In sum, while breast cancer survivors demonstrate good adjustment on general distress indices following treatment, some women are at risk for sustained distress. Moreover, significant cancer-related concerns are prevalent and may be important intervention targets.

Auditory event-related potentials in subcortical vascular cognitive impairment and in Alzheimer's disease.

BACKGROUND: Few studies exist on ERPs and patients with subcortical vascular cognitive impairment (SVCI). This latter is a quite homogeneous subtype of vascular dementia whose cognitive profile is quite different from that of Alzheimer disease (AD). AIMS: The present study aims at comparing the ERPs profile both in patients with SVCI and in patients with AD. SUBJECTS AND METHODS: ERPs and psychometric tests were collected from 39 healthy elderly controls, 51 patients with SVCI and 43 patients with AD. Subjects mentally count high pitched target tones that were randomly intermixed with low pitched frequent tones. We measured ERPs latencies (N1, P2, N2 and P3), and interpeak latencies (N1-P3, N1-P2, N1-N2). RESULTS: Grand averaged potentials in SVCI showed a significant increase of P3 latency. AD patients showed a prolongation of N1, P2, N2, P3 latencies. As far as interpeak latencies are concerned, SVCI patients showed a significant prolongation of N1-P3, AD patients had a significant increase of N1-N2, and N1-P3 intervals. When all patients were considered as a single group, correlation of neuropsychological tests scores showed a significant negative relationship between P300 latency and, respectively, Mini Mental Status Examination, auditive and visual span forward. In both groups, ERPs latency sensitivity, was low, whilst specificity values were quite high. CONCLUSIONS: Our finding suggest that these two dementing diseases have different electrophysiologic features that may be related to their specific underlying pathogenetic mechanism; in particular, we hypothesise that, differently from AD, P300 latency prolongation characterizes the early stage of SVCI. So, this ERPs approach could be helpful to detect early alterations of the attentional/working-memory functions in patients with subcortical ischaemic vascular disease.

Implementation of myocardial perfusion imaging in the early triage of patients with suspected acute coronary syndromes.

The risk of overlooking an underlying acute coronary syndrome remains an important challenge in patients complaining of chest pain but who have a non-diagnostic ECG (CP). Indeed, myocardial scintigraphy associated with exercise testing (exercise SPET) represents a valuable tool for excluding coronary artery disease (CAD) especially in patients with CP and delayed presentation to the emergency department. We sought to implement diagnoses of CAD in the early triage of CP patients by exercise gated SPET and compare diagnoses with outcomes. A total of 306 consecutive patients presenting with CP were found to be free of CAD at first line work-up including clinical evaluation, markers of myocardial injury and echocardiogram. These patients were studied initially with exercise SPET, and those with perfusion defects underwent angiography, while those with normal scans were discharged and followed up. Patients with positive scans (34%, n=105) had documented coronary stenoses in 43% (n=45); patients with negative scans (66%, n=201) had evidence of non-fatal coronary events at 6 months in 1.5% (n=3). When imaging was analysed with gating by the presence of transmural perfusion defects associated with wall motion abnormalities (n=86), only one patient, among 19 excluded, was recognized as having coronary stenosis by angiography (SPET vs gated SPET: negative predictive value 98.5% and 98%, respectively, P=NS; diagnostic accuracy 79% and 85%, respectively; P< or =0.03). Therefore, implementation of myocardial perfusion imaging in the early triage of patients with suspected acute coronary syndromes was effectively obtained by early exercise gated SPET, especially in patients with transmural myocardial perfusion defects associated with wall motion abnormalities.

Transcranial magnetic stimulation after pure motor stroke.

OBJECTIVES: The objective of this study was to assess the sensitivity of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in demonstrating the possible subclinical impairment of the corticospinal pathway after recovery, in patients with a clinical history of pure motor stroke (PMS) due to a single lacunar infarct detectable by magnetic resonance imaging (MRI). METHODS: MEPs were recorded from the first dorsal interosseous muscle of 20 healthy subjects and 40 patients, 6 months or more after PMS onset. Patients were evaluated clinically by means of the NIH stroke scale, the Medical Research Council (MRC) scale and the Barthel Index. The patients with full hand strength recovery and the normal controls were also tested by means of the 9-hole peg test. RESULTS: Motor threshold (MT), MEP amplitude and central motor conduction time (CMCT) of the affected side were significantly different from those of the normal side and of the control subjects. MT, MEP amplitude and CMCT obtained after stimulation of the affected hemisphere were significantly correlated with the MRC scale values of the affected hand. Eighty-six percent of patients with persistent hand strength deficit showed MEP abnormalities. In 21 patients with complete clinical recovery, a significant increase in MT and decrease in MEP amplitude on the affected side were observed. CONCLUSIONS: After PMS, neurophysiological changes may persist despite complete clinical recovery. TMS represents a sensitive tool that enables to demonstrate objectively the clinical and subclinical impairment of the corticospinal pathway.

Early detection of myocardial ischaemia in the emergency department by rest or exercise (99m)Tc tracer myocardial SPET in patients with chest pain and non-diagnostic ECG.

Chest pain (CP) represents a frequent reason for presentation at the emergency department (ED). A large proportion of patients have non-diagnostic ECG on presentation, and in many cases several hours have elapsed since onset of symptoms. Acute rest myocardial scintigraphy (rest SPET) has been shown to have a relevant role in the detection of patients at risk for coronary events, but its sensitivity and negative predictive value are optimal only within the first 3 h following onset of symptoms. In those with delayed presentation, exercise SPET alone, as a screening approach, appears more promising, but its feasibility and diagnostic role in the ED are still unresolved. A total of 231 consecutive patients with a recent-onset (<24 h) first episode of CP had a negative first-line work-up including ECG, troponins, creatine kinase-MB and echocardiography. These patients were considered at low risk for short-term coronary events. Patients were studied with rest SPET if they presented <3 h after onset of CP and exercise SPET if they presented after > or =3 h. The end-points of the study were detection of significant coronary artery disease (CAD) by angiography and major coronary events or cardiac death at 6 months. Eighty patients (35%) underwent rest SPET, while 151 (65%) underwent exercise SPET. Two of the 159 patients with negative SPET had evidence of critical CAD at 6-month follow-up (one patient in the rest SPET group and one in the exercise SPET group; P=NS). Of the 72 patients (31%) with a positive scan, 34 (15%) had documented CAD (16 patients in the rest SPET group and 18 in the exercise SPET group; P=NS). Sensitivity, specificity, accuracy and predictive value were not statistically different between the two groups. In conclusion, the accuracy of exercise SPET in patients with CP and delayed presentation to the ED is comparable to that of validated rest SPET in patients with early presentation. Owing to the high negative predictive value (99%), exercise SPET is especially valuable as a screening tool for the exclusion of CAD in low-risk patients and implementation of early discharge.

Transcranial magnetic stimulation in Alzheimer disease: motor cortex excitability and cognitive severity.

To study the possible changes of cortical excitability in the Alzheimer disease (AD) by transcranial magnetic stimulation (TMS) and to evaluate their eventual correlation with its stage twenty-one AD patients and 18 normal controls underwent TMS. Motor threshold, amplitudes of motor evoked potentials (MEPs), central motor conduction time (CMCT) and silent period (SP) were considered. The motor threshold in AD patients was lower than in normal subjects with a significant correlation between the stage of cognitive severity. The amplitude of MEPs was increased and the SP duration was reduced in AD patients. No significant differences were obtained for CMCT. These findings could suggest a correlation between increased motor cortical excitability and cognitive severity. Moreover, the increased cortical excitability could represent a key to understand the mechanism of AD and may have implication for novel treatment strategies.

Preschoolers' use of reflective properties: identification of reflections on partially transparent surfaces.

This exploratory study extended past studies of children's ability to reference the mirror as a tool in locating the source of reflected images to preschoolers' ability to use the affordances of a transparency. Thirty-six children (3.5 to 5 years old) were shown nonreflected lights and lights reflected on a partially transparent, glassy surface. Children did not spontaneously locate the source of the reflected image. However, they were able to verbally discriminate reflected from nonreflected images following training. These findings indicate that, although preschoolers may not spontaneously use transparencies as a perceptual tool, the ability to distinguish visual differences of reflected from nonreflected images on transparencies is likely within preschool children's developmental capacity.

Capecitabine and oxaliplatin in advanced colorectal cancer: a dose-finding study.

PURPOSE: Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer (ACRC). The aim of this dose-finding trial was to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities (DLTs) and the activity of the combination in patients with advanced colorectal cancer. PATIENTS AND METHODS: Twenty-five chemotherapy-pretreated patients received the combination of capecitabine and oxaliplatin. Capecitabine was administered orally twice a day continuously for 14 days in doses ranging from 1,650 to 2,500 mg/m2/d, and oxaliplatin was administered as a two-hour infusion on day 1 using dose, ranges from 100 to 130 mg/m2 repeated every three weeks. RESULTS: Twenty-five patients were assessable for toxicity, and DLTs were diarrhea (grade > or = 3: 27%) and stomatitis (grade > or = 3: 9%) at dose level VI. Dose level V (capecitabine 2500 mg/m2 and oxaliplatin 120 mg/m2) was found to be the MTD. Hematological toxicity was minimal, overall neurotoxicity (grade 1-4) was 27% with 1% grade 3-4. A global response rate was 17% (95% confidence interval (95% CI): 2%-32%) and the median overall survival was 12 months. CONCLUSION: The recommended dose for further phase II studies is capecitabine 2,500 mg/m2/d with intermittent schedule and oxaliplatin 120 mg/m2 every three weeks. The toxicities were mainly gastrointestinal: diarrhea, stomatitis and vomiting. This combination should be studied in phase II trials in advanced colorectal.

Competition at silent synapses in reinnervated skeletal muscle.

Synaptic connections are made and broken in an activity-dependent manner in diverse regions of the nervous system. However, whether activity is strictly necessary for synapse elimination has not been resolved directly. Here we report that synaptic terminals occupying motor endplates made electrically silent by tetrodotoxin and alpha-bungarotoxin block were frequently displaced by regenerating axons that were also both inactive and synaptically ineffective. Thus, neither evoked nor spontaneous activation of acetylcholine receptors is required for competitive reoccupation of neuromuscular synaptic sites by regenerating motor axons.

Co-regulation of synaptic efficacy at stable polyneuronally innervated neuromuscular junctions in reinnervated rat muscle.

1. Intracellular recordings and quantal analysis of synaptic transmission were made at neuromuscular junctions receiving stable convergent innervation in reinnervated rat lumbrical muscles, following recovery from chronic nerve conduction block. The polyneuronally innervated motor endplates (pi-junctions) were identified by vital staining of lateral plantar nerve (LPN) and sural nerve (SN) motor terminals, using the activity-dependent staining properties of the aminostyryl dyes RH414 and FM1-43, respectively. 2. Endplate depolarisation and quantal content per unit area varied by more than a factor of ten ( approximately 0.1-1. 4 quanta microm-2) between fibres. However, the stable pi-junctions produced nearly equivalent endplate depolarisations and quantal content per unit area, suggesting that synaptic strengths were co-regulated at these motor endplates. Quantal content per unit area was also independent of the size of individual synaptic inputs, or whether one, both or neither input was judged sufficient to produce suprathreshold or subthreshold endplate depolarisations. 3. Simultaneous excitation of convergent LPN and SN inputs from some pi-junctions resulted in profound non-linear summation, and in some cases complete occlusion of the response of the smaller input. The amplitude of the smaller, test responses recovered with a time constant of 2.1 +/- 0.5 ms (mean +/- s.e.m.) on varying the interval between paired stimuli, of similar order to the time constant of repolarisation of the conditioning endplate potential. 4. The data show that it is not necessary for a motor nerve terminal to occupy most of an endplate, or to produce a suprathreshold response in order to become stable. The occlusion of linear summation, similar to that described previously at polyneuronal junctions in neonates, suggests that convergent inputs comprising interdigitated synaptic boutons evoke self-contained synaptic responses at endplates, and that these are non-co-operative with respect to overall endplate depolarisation or safety margin for synaptic transmission.

Simultaneous dobutamine stress echocardiography and 99mTc-tetrofosmin three-head single-photon emission computed tomography in patients with suspected coronary artery disease.

OBJECTIVES AND BACKGROUND: Dobutamine stress echocardiography and 99mTc-tetrofosmin single-photon emission computed tomography (T-SPECT) were performed simultaneously in subjects in whom coronary artery disease (CAD) had been proven or excluded at coronary angiography, in order to establish their accuracy and agreement in the diagnosis of CAD, and in localisation and evaluation of the extension of ischaemia. No simultaneous comparison of the two techniques has been performed previously. METHODS: Seventy patients (50 men, mean age 63 +/- 10 years, 21 with previous myocardial infarction) underwent simultaneous dobutamine stress echocardiography and T-SPECT. The response to stress was blindly and independently analysed, adopting a 16-region segmentation and referring to the three major coronary arteries. RESULTS: Sixty-two patients (agreement 89%, kappa = 0.776) and 91% of left ventricular regions (kappa = 0.665) were classified concordantly, independently of the presence or absence of previous myocardial infarction (90%, kappa = 0.740 versus 91%, kappa = 0.589, respectively). At coronary angiography, 47 patients had CAD (disease prevalence 67%). The sensitivity and specificity of stress echocardiography for the diagnosis of anterior descending, circumflex and right coronary artery disease were 62, 78 and 73%, and 79, 79 and 83%, respectively. The corresponding values for T-SPECT were 70, 75 and 78%, and 94, 79 and 90%, respectively. CONCLUSIONS: These data indicate a high concordance between wall motion abnormalities observed using stress echocardiography and perfusion defects observed using T-SPECT; their sensitivity in identifying critical stenoses was similar. Inadequate stressor amounts, and less frequently hyperdynamic regional response may reduce the accuracy of stress echocardiography, while dobutamine effects on coronary flow may prevent T-SPECT from showing subtle flow maldistributions in the presence of worsened wall motion.

The clinical impact of dynamic intraventricular obstruction during dobutamine stress echocardiography.

We selected 73 consecutive patients without myocardial-infarction, hypertrophic cardiomyopathy or hypertension complaining of effort chest discomfort/dyspnoea, and/or reporting exercise ischaemic ECG changes, and submitted them to simultaneous dobutamine stress echocardiography (DSE) and 99mTc tetrofosmin SPECT (T SPECT) and to coronary angiography to evaluate the clinical impact of intraventricular obstruction (IVO) during dobutamine infusion. Sixteen patients (22%, 7 males, mean age+/-SD 63+/-8 years, group 1) developed IVO (mean CW Doppler velocity+/-SD: 3.8+/-1.0 m/s) and 57 (41 males, mean age+/-SD 63+/-10 years, group 2) did not. The two groups had similar incidence of angina and ischaemic ECG changes at exercise tolerance test. DSE did not demonstrate wall motion abnormalities in any group 1 patient while T SPECT showed a perfusion defect in the only one with coronary artery disease (CAD). DSE reproduced symptoms in a higher percentage of patients with than without IVO, while there was no statistical difference in the reproduction of ischaemic ECG changes, despite CAD prevalence was much lower in group 1. Group 1 patients remained asymptomatic on beta-blockers at 12-month follow-up. Dobutamine-induced IVO, by reproducing symptoms, suggests that IVO plays a role in the clinical setting in patients without CAD complaining of unexplained reduced effort tolerance who should undergo DSE.

Effects of potassium channel blockers on synaptic plasticity in the corticostriatal pathway.

High-frequency stimulation (HFS) of the cerebral cortex or underlying white matter usually induces long-term depression (LTD) in the corticostriatal pathway. Long-term potentiation (LTP) has been described in striatal cells exposed to extracellular tetraethylammonium (TEA). The facilitating effect of TEA may be due to blockade of K+ channels in the postsynaptic neurone or alternatively to presynaptic effects on the release of neurotransmitters such as glutamate or dopamine. We compared the effects of HFS on LTP in striatal cells in four groups of neurones. HFS in control conditions induced LTD (-28.6 +/- 2.0% at 20 min, n = 10) whereas HFS in extracellular TEA (30 mM) induced LTP (+51.0 +/- 24.2% at 20 min, n = 7). LTP was not induced in cells loaded with intracellular Cs (-20.3 +/- 11.4% at 20 min, n = 10) or intracellular TEA (-11.8 +/- 8.9% at 20 min, n = 10), despite comparable effects on postsynaptic responses to HFS. Since the effects of the intracellular K+ channel blockers are limited to the cell being recorded from. these findings suggest that the facilitating effect of extracellular TEA on LTP induction involves a presynaptic action.

Randomised, double-blind, placebo-controlled study of pivagabine in neurasthenia.

One hundred and eighteen patients with neurasthenia, as defined by ICD 10 (International Classification of Diseases), participated in a randomised, double-blind, placebo-controlled trial of pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg). Pivagabine 1800 mg/d was administered orally for four weeks. At the end of the trial, active medication was significantly superior to placebo on the Clinical Global Impression (CGI) improvement of illness scale. In addition, pivagabine treatment reduced the physical and mental fatigability of patients, and increased their sense of well-being.