Hyperventilation and seizures in an adolescent female.

A 16 year-old girl was admitted after suffering from recurrent episodes of dyspnea and stridor, cyanosis, loss of contact, stiffening of all four limbs, clenching of the jaw and eye retroversion that lasted for a few seconds to a minute, followed by slow recovery of consciousness without any loss of sphincter control. These symptoms began at the age of 11 and worsened over time. Prolonged rate corrected QT intervals was observed with an ECG. Two cardio-respiratory monitorings were performed (one during daytime hours while the patient was awake, and one at night time while the patient slept). Daytime recordings showed 17 central apnoeas and 97 central hypopneas, with an apnea-hypopnea index (AHI) of 13.2 events/hour, that were associated with severe oxyhemoglobin desaturation. In contrast, night time recordings were normal (AHI=1.1 events/hour). The patient underwent diurnal monitoring of transcutaneous pCO2(PtcCO2), transcutaneous O2(PtcO2), SpO2 and end tidal CO2 (PETCO2), with simultaneous monitoring of regional cerebral oxymetry (rSO2) which showed values of PtcCO2 between 8 and 15 mmHg, suggesting several episodes of marked hyperventilation. Twenty-nine episodes of severe arterial desaturation (SpO2<50%) were registered, all after the same number of apnea events, with ascent of PtcO2 up to 28 mmHg at the end of apnea. During the final phase of apnea, the patient showed cyanosis, contact disturbance, grimaces, oral movements of rhyme, and, on three occasions, partial seizures. A mask was packaged and applied daytime to the face of the patient during episodes of hyperventilation to prevent, together with a psychiatric follow up, rapid falls of PaCO2 levels determining central apnoeas.

From Observed Action Identity to Social Affordances.

Others' observed actions cause continuously changing retinal images, making it challenging to build neural representations of action identity. The monkey anterior intraparietal area (AIP) and its putative human homologue (phAIP) host neurons selective for observed manipulative actions (OMAs). The neuronal activity of both AIP and phAIP allows a stable readout of OMA identity across visual formats, but human neurons exhibit greater invariance and generalize from observed actions to action verbs. These properties stem from the convergence in AIP of superior temporal signals concerning: (i) observed body movements; and (ii) the changes in the body-object relationship. We propose that evolutionarily preserved mechanisms underlie the specification of observed-actions identity and the selection of motor responses afforded by them, thereby promoting social behavior.

Histological assessment of a chronically implanted cylindrically-shaped, polymer-based neural probe in the monkey.

Objective.Previous studies demonstrated the possibility to fabricate stereo-electroencephalography probes with high channel count and great design freedom, which incorporate macro-electrodes as well as micro-electrodes offering potential benefits for the pre-surgical evaluation of drug resistant epileptic patients. These new polyimide probes allowed to record local field potentials, multi- and single-unit activity (SUA) in the macaque monkey as early as 1 h after implantation, and yielded stable SUA for up to 26 d after implantation. The findings opened new perspectives for investigating mechanisms underlying focal epilepsy and its treatment, but before moving to possible human application, safety data are needed. In the present study we evaluate the tissue response of this new neural interface by assessing post-mortem the reaction of brain tissue along and around the probe implantation site.Approach.Three probes were implanted, independently, in the brain of one monkey (Macaca mulatta) at different times. We used specific immunostaining methods for visualizing neuronal cells and astrocytes, for measuring the extent of damage caused by the probe and for relating it with the implantation time.Main results.The size of the region where neurons cannot be detected did not exceed the size of the probe, indicating that a complete loss of neuronal cells is only present where the probe was physically positioned in the brain. Furthermore, around the probe shank, we observed a slightly reduced number of neurons within a radius of 50µm and a modest increase in the number of astrocytes within 100µm.Significance.In the light of previous electrophysiological findings, the present data suggest the potential usefulness and safety of this probe for human applications.

Osteochondral avulsion fracture of the posteromedial tibial plateau.

Posteromedial tibial plateau avulsion fracture caused by semimembranosus muscle is not easy to detect by X-ray. The literature regarding this issue is poor, also mechanism is extensively disputable. This lesion was often connected to an anterior cruciate ligament (ACL) rupture and medial meniscal horn lesion. In this work, we described a posteromedial tibial plateau avulsion fracture at the semimembranosus insertion. In particular, we referred to the surgical treatment of those transversal osteochondral fractures.

Versatile, modular 3D microelectrode arrays for neuronal ensemble recordings: from design to fabrication, assembly, and functional validation in non-human primates.

OBJECTIVE: Application-specific designs of electrode arrays offer an improved effectiveness for providing access to targeted brain regions in neuroscientific research and brain machine interfaces. The simultaneous and stable recording of neuronal ensembles is the main goal in the design of advanced neural interfaces. Here, we describe the development and assembly of highly customizable 3D microelectrode arrays and demonstrate their recording performance in chronic applications in non-human primates. APPROACH: System assembly relies on a microfabricated stacking component that is combined with Michigan-style silicon-based electrode arrays interfacing highly flexible polyimide cables. Based on the novel stacking component, the lead time for implementing prototypes with altered electrode pitches is minimal. Once the fabrication and assembly accuracy of the stacked probes have been characterized, their recording performance is assessed during in vivo chronic experiments in awake rhesus macaques (Macaca mulatta) trained to execute reaching-grasping motor tasks. MAIN RESULTS: Using a single set of fabrication tools, we implemented three variants of the stacking component for electrode distances of 250, 300 and 350 µm in the stacking direction. We assembled neural probes with up to 96 channels and an electrode density of 98 electrodes mm-2. Furthermore, we demonstrate that the shank alignment is accurate to a few µm at an angular alignment better than 1°. Three 64-channel probes were chronically implanted in two monkeys providing single-unit activity on more than 60% of all channels and excellent recording stability. Histological tissue sections, obtained 52 d after implantation from one of the monkeys, showed minimal tissue damage, in accordance with the high quality and stability of the recorded neural activity. SIGNIFICANCE: The versatility of our fabrication and assembly approach should significantly support the development of ideal interface geometries for a broad spectrum of applications. With the demonstrated performance, these probes are suitable for both semi-chronic and chronic applications.

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites.

OBJECTIVE: Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. APPROACH: Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 µm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. MAIN RESULTS: Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. SIGNIFICANCE: With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the brain of a monkey, which suggests the potential usefulness of this probe for human applications.

Decreased CSF concentrations of homovanillic acid and gamma-aminobutyric acid in Alzheimer's disease. Age- or disease-related modifications?

Fifteen patients, 48 to 72 years old, with Alzheimer's disease were studied. Clinical status was assessed by neurologic and neuropsychologic examinations and psychometric testing. Patients were divided into two groups on the basis of clinical assessment: group 1, little mental deterioration, and group 2, serious mental deterioration. Nineteen subjects, 27 to 72 years old, without neurologic disease served as controls. Levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and gamma-aminobutyric acid (GABA) were determined in lumbar CSF by fluorimetric or radioreceptor binding (GABA) methods. The HVA concentrations increased with age in the controls, whereas the GABA levels decreased with age and 5-HIAA levels were not modified. When compared with the age-matched controls, the patients with Alzheimer's disease showed low concentrations of HVA but not of 5-HIAA or GABA. The decrease in HVA level was more pronounced in patients with severe mental deterioration and therefore appeared to be disease related.

Association between salt sensitivity and insulin concentrations in patients with hypertension.

This study was performed in 28 patients with mild to moderate hypertension, classified as being either salt sensitive or salt resistant on the basis of the percent decrement in mean arterial blood pressure (MAP) seen 7 days after daily salt intake was decreased from 220 to 30 mmol/L. Ten patients had a percent decrease of MAP > 10% and were defined as being salt sensitive. Salt resistance was defined as a percent decrease in MAP of < 3% and eight patients satisfied this criterion. Both plasma glucose and insulin concentrations following a 75-g oral glucose challenge were significantly higher after the high-salt diet in the salt-sensitive patients. Furthermore, there were correlations of marginal statistical significance between the decrease in MAP after the low-salt diet and the plasma glucose (r = 0.32, P < .10) and insulin (r = 0.38, P < .06) responses to oral glucose. These data are consistent with the view that there is an association between resistance to insulin-mediated glucose disposal and salt sensitivity in patients with high blood pressure.

Hyperinsulinemia in a normal population as a predictor of non-insulin-dependent diabetes mellitus, hypertension, and coronary heart disease: the Barilla factory revisited.

The study was initiated to evaluate the ability of hyperinsulinemia (as a surrogate measure of insulin resistance) to predict the development in a previously healthy population of three putative outcomes of this abnormality--glucose intolerance, hypertension, and coronary heart disease (CHD). The study involved defining the incidence at which these changes occurred between 1981 and 1993 to 1996 in 647 individuals who were free of any disease when initially studied. The study population consisted of approximately 90% of the subjects evaluated in 1981, divided into quartiles on the basis of the plasma insulin response to a glucose challenge as determined in 1981. The results indicated that the 25% of the population with the highest insulin response in 1981 had significant (P < .001) increases in the incidence of impaired glucose tolerance (IGT) or type 2 diabetes (eightfold), hypertension (twofold), or CHD (threefold). Furthermore, the ability of hyperinsulinemia to predict the three clinical endpoints was independent of differences in age, gender, or body mass index (BMI). Finally, if CHD is considered the clinical endpoint, multiple logistic regression analysis indicates that the values for plasma triglyceride (TG) and mean arterial blood pressure ([MAP] as measured in 1981) also predict the development of CHD. These results indicate that the untoward clinical effects of insulin resistance and/or compensatory hyperinsulinemia, glucose intolerance, hypertension, and CHD clearly can develop in less than 15 years.

A multi-center study: clinical practices of HIV infected patients on CAPD/CCPD.

Our statistics reveal the average patient in our study to be a young black male with a history of IVDA with CAPD as the initial dialysis modality. He was most often trained on a mechanical assist device, but he still developed frequent peritonitis episodes, predominantly gram positive. His survival rate was less than 2 years, but he was able to remain independent until he died. Our fears about caring for the HIV infected individual cannot be denied. Even though we may never be truly comfortable when caring for someone with this disease, it is possible to train them to perform home peritoneal dialysis safely and effectively. By doing this, we can preserve the patients' independence and maintain their dignity while they cope with this overwhelming illness.

[Activity of fenfluramine in obese subjects. Relation between dosage, plasma concentration of the drug and its effect on weight loss]. / Attività della fenfluramina in soggetti obesi. Rapporti tra dosi, concentrazioni plasmatiche di farmaco e suoi effetti sul calo ponderale.

Twenty-one patients have been submitted to hypocaloric diet and anorexigenic treatment with fenfluramine at variable doses. The weight loss, the plasma level concentration of fenfluramine (F) and norfenfluramine (NF) have been evaluated during a period of about 9 weeks. Statistical analysis demonstrates a significant weight loss and a highly significant correlation between the dose of administered drug and plasma level concentration of F and NF. No correlation instead has been found between weight loss and the dose administered of F, nor between weight loss and the dose administered of F, nor between weight loss and F and/or NF plasma level concentration.

Fabrication and characterization of a high-resolution neural probe for stereoelectroencephalography and single neuron recording.

This paper reports on the design, fabrication, and characterization of neural probes for stereoelectroencephalography (SEEG). The probe specifically targets focal epilepsy as key application. However, probes of this type can also be used for the diagnosis and treatment of other neural dysfunctions such as Parkinson's disease or tremor, typically requiring deep brain probes. The probe fabrication, of which most processes are parallel batch processes, relies on a novel fabrication concept for rolling and gluing thin film polyimide sheets with integrated electrodes into permanent cylindrical shapes with diameters down to 800 µm. The SEEG probes, comprise several macro-electrodes designed to record local field potentials, and micro-electrodes positioned in-between, dedicated to monitoring single unit activity, with a total channel count of 32, despite the small diameter. While platinum micro-electrodes with a diameter of 35 µm have impedances of about 255 kΩ at 1 kHz, impedance values down to about 1.5 kΩ have been measured for the macro-electrodes. The devices have shown good compatibility with magnetic resonance imaging in a 9.4 T magnet, enabling the precise post-operative probe localization within the brain.

Individual and social learning processes involved in the acquisition and generalization of tool use in macaques.

Macaques can efficiently use several tools, but their capacity to discriminate the relevant physical features of a tool and the social factors contributing to their acquisition are still poorly explored. In a series of studies, we investigated macaques' ability to generalize the use of a stick as a tool to new objects having different physical features (study 1), or to new contexts, requiring them to adapt the previously learned motor strategy (study 2). We then assessed whether the observation of a skilled model might facilitate tool-use learning by naive observer monkeys (study 3). Results of study 1 and study 2 showed that monkeys trained to use a tool generalize this ability to tools of different shape and length, and learn to adapt their motor strategy to a new task. Study 3 demonstrated that observing a skilled model increases the observers' manipulations of a stick, thus facilitating the individual discovery of the relevant properties of this object as a tool. These findings support the view that in macaques, the motor system can be modified through tool use and that it has a limited capacity to adjust the learnt motor skills to a new context. Social factors, although important to facilitate the interaction with tools, are not crucial for tool-use learning.

From monkey mirror neurons to primate behaviours: possible 'direct' and 'indirect' pathways.

The discovery of mirror neurons (MNs), deemed to be at the basis of action understanding, could constitute the potential solution to the 'correspondence problem' between one's own and others' action that is crucial for of imitative behaviours. However, it is still to be clarified whether, and how, several imitative phenomena, differing in terms of complexity and cognitive effort, could be explained within a unified framework based on MNs. Here we propose that MNs could differently contribute to distinct imitative behaviours by means of two anatomo-functional pathways, subjected to changes during development. A 'direct mirror pathway', directly influencing the descending motor output, would be responsible for neonatal and automatic imitation. This proposal is corroborated by some new behavioural evidences provided here. During development, the increased control of voluntary movements and the capacity to efficiently suppress automatic motor activation during action observation assign to the core MNs regions essentially perceptuo-cognitive functions. These functions would be exploited by an 'indirect mirror pathway' from the core regions of the MN system to prefrontal cortex. This latter would play a key role in parsing, storing and organizing motor representations, allowing the emergence of more efficient and complex imitative behaviours such as response facilitation and true imitation.

Hyperinsulinaemia, obesity, and syndrome X.

OBJECTIVE: The major aim of this study was to compare various aspects of carbohydrate, insulin, and lipoprotein metabolism, serum uric acid concentration, and blood pressure in normal subjects stratified on the basis of both plasma insulin concentration and degree of obesity. The hypothesis to be tested was that hyperinsulinaemia, per se, was associated with relative glucose intolerance, higher triglyceride and uric acid concentrations, lower high-density lipoprotein cholesterol concentration and higher blood pressure, irrespective of degree of obesity. DESIGN: This represents a case-control study, in which normal volunteers were subdivided into four equal groups based upon degree of obesity and plasma insulin response to a 74 g oral glucose challenge. SETTING: The study was performed in the out-patient clinic of a university hospital. SUBJECTS: Sixty-four individuals were recruited for this study, subdivided into four groups based upon their plasma insulin concentration and body mass index. Subjects were classified as hyperinsulinaemic if their plasma insulin concentrations in response to an oral glucose challenge were more than two standard deviations above the mean of 732 volunteers previously studied [1]. Obesity was defined as a body mass index of > 30 kg m-2, and individuals were classified as non-obese if their body mass index was < 27.0 kg m-2. Based upon these criteria, four experimental groups were created: (i) non-obese hyperinsulinaemic (NOB hyper); (ii) obese hyperinsulinaemic (OB hyper); (iii) non-obese normoinsulinaemic (NOB normo); and (iv) obese normoinsulinaemic (OB normo). MAIN OUTCOME MEASURES: Subject groups were compared on the basis of the integrated plasma glucose response to a 75 g oral glucose challenge, fasting plasma triglyceride, cholesterol, high-density lipoprotein cholesterol, and uric acid concentrations, and blood pressure. RESULTS: Mean (+/- standard error of the mean) integrated plasma glucose response area for 2 h following a 75 g oral glucose load was significantly higher (13.4 +/- 0.4 vs. 11.0 +/- 0.4 mmol l-1, P < 0.001) in the hyperinsulinaemic group, as were the fasting triglyceride levels (2.4 +/- 0.2 vs. 1.4 +/- 0.1 mmol l-1, P < 0.001) and uric acid (5.3 +/- 0.2 vs. 4.4 +/- 0.2 mmol l-1, P < 0.05) concentrations. In contrast, high-density lipoprotein concentrations were lower in the hyperinsulinaemic group (1.06.0.05 vs. 1.32 +/- 0.05 mmol l-1, P < 0.001). In addition, blood pressure was higher in the hyperinsulinaemic group (136 +/- 5/87 +/- 2 vs. 123 +/- 2/82 +/- 1 mmHg, P < 0.05). Furthermore, when each of the two groups were divided into obese (n = 16) and non-obese (n = 16) groups, all of the differences outlined above persisted. These changes were independent of age, gender distribution, generalized and abdominal obesity, cigarette smoking, and estimated physical activity. CONCLUSIONS: The cluster of changes subsumed under the heading of syndrome X are closely associated with hyperinsulinaemia (and presumably insulin resistance), and can be discerned irrespective of degree of obesity.

Dissociation between urinary albumin excretion and variables associated with insulin resistance in a healthy population.

OBJECTIVES: To see if the cluster of metabolic and haemodynamic variables defined as comprising Syndrome X varied as a function of urinary albumin excretion (UAE) rate in a healthy population. DESIGN: A cross-sectional, population-based study. SETTING: A factory in Italy. SUBJECTS: Two hundred and twenty-five healthy volunteers, 115 men and 110 women. OUTCOME MEASURES. Measurements were made of the plasma glucose and insulin responses to oral glucose, fasting triglyceride (TG) and high density lipoprotein (HDL)-cholesterol concentrations, blood pressure, and UAE rates. RESULTS: Only five of the 225 volunteers had micro-albuminuria, defined as a UAE rate > 2 micrograms min-1, and the UAE rate was < 5 micrograms min-1 in 80% of the volunteers. Significant variations in the metabolic and haemodynamic variables measured were not associated with any differences in UAE. Finally, significant relationships were found between various measures of plasma insulin concentration and plasma glucose response to oral glucose, plasma TG and HDL-cholesterol concentrations, and mean arterial blood pressure, independent of variations in age, body mass index, ratio of waist-to-hip girth, and UAE rates. CONCLUSION: The widespread variability in plasma glucose and insulin responses, plasma TG and HDL-cholesterol concentrations, and blood pressure that are seen in the population at large cannot be attributed to variations in UAE rate.