Lactate, not glucose, up-regulates mitochondrial oxygen consumption both in sham and lateral fluid percussed rat brains

OBJECTIVE: Failure of energy metabolism after traumatic brain injury may be a major factor limiting outcome. Although glucose is the primary metabolic substrate in the healthy brain, the well documented surge in tissue lactate after traumatic brain injury suggests that lactate may provide an energy need that cannot be met by glucose. We hypothesized, therefore, that administration of lactate or the combination of lactate and supraphysiological oxygen may improve mitochondrial oxidative respiration in the brain after rat fluid percussion injury. We measured oxygen consumption (VO2) to determine what effects glucose, lactate, oxygen, and the combination of lactate and oxygen have on mitochondrial respiration in both injured and uninjured rat brain tissue. METHODS: Anesthetized Sprague-Dawley rats were intubated and ventilated with either 0.21 or 1.0 fraction of inspired oxygen (FIO2). Brain tissue from acute sham animals was subjected in vitro to 1.1 mM, 12 mM and 100 mM concentrations of glucose and L-lactate. In another group, injury (fluid percussion injury of 2.5 +/- 0.02 atmospheres) was induced over the left hemisphere. The VO2 of mug amounts of brain tissues were measured in a microrespirometry system (Cartesian diver). RESULTS: The VO2 was found to be independent of glucose concentrations, but dose-dependent for lactate. Moreover, the lactate dependent VO2s were all significantly higher than those generated by glucose. Injured rats on FIO2 0.21 had brain tissue VO2 rates that were significantly lower than those of shams or preinjury levels. In injured rats treated with FIO2 1.0, the reduction in VO2 levels was prevented. Injured rats that received an intravenous infusion of 100 mM lactate had VO2 rates that were significantly higher than those obtained with FIO2 1.0. Combined treatment further boosted the lactate generated VO2 rates by approximately 15%. CONCLUSION: Glucose sustains mitochondrial respiration at a low level "fixed" rate because, despite increasing its concentration nearly 100-fold, it cannot up-regulate VO2 after fluid percussion injury. Lactate produces a dose-dependent VO2 response, possibly enabling mitochondria to meet the increased energy needs of the injured brain.

One-Hertz transcranial magnetic stimulation over the frontal eye field induces lasting inhibition of saccade triggering

The aim of the study was to examine the effect of low-frequency repetitive transcranial magnetic stimulation on saccade triggering. In five participants, a train of 600 pulses with a frequency of 1 Hz was applied over the right frontal eye field and--as control condition--over the vertex. After repetitive transcranial magnetic stimulation application, oculomotor performance was evaluated with an overlap paradigm. The results show that the repetitive transcranial magnetic stimulation effect was specific for frontal eye field stimulation. Saccade latencies were found to be increased bilaterally for several minutes after the stimulation, and the time course of recovery was different for the ipsilateral and contralateral sides. The results are discussed in the light of possible local and remote repetitive transcranial magnetic stimulation effects on the oculomotor network.

Contrast-enhanced transcranial Doppler ultrasound for diagnosis of patent foramen ovale

The suspected cause of clinical manifestations of patent foramen ovale (PFO) is a transient or a permanent right-to-left shunt (RLS). Contrast-enhanced transcranial Doppler ultrasound (c-TCD) is a reliable alternative to transesophageal echocardiography (TEE) for diagnosis of PFO, and enables also the detection of extracardiac RLS. The air-containing echo contrast agents are injected intravenously and do not pass the pulmonary circulation. In the presence of RLS, the contrast agents bypass the pulmonary circulation and cause microembolic signals (MES) in the basal cerebral arteries, which are detected by TCD. The two main echo contrast agents in use are agitated saline and D-galactose microparticle solutions. At least one middle cerebral artery (MCA) is insonated, and the ultrasound probe is fixed with a headframe. The monitored Doppler spectra are stored for offline analysis (e.g., videotape) of the time of occurrence and number of MES, which are used to assess the size and functional relevance of the RLS. The examination is more sensitive, if both MCAs are investigated. In the case of negative testing, the examination is repeated using the Valsalva maneuver. Compared to TEE, c-TCD is more comfortable for the patient, enables an easier assessment of the size and functional relevance of the RLS, and allows also the detection of extracardiac RLS. However, c-TCD cannot localize the site of the RLS. Therefore, TEE and TCD are complementary methods and should be applied jointly in order to increase the diagnostic accuracy for detecting PFO and other types of RLS.

An integrative transcranial magnetic stimulation mapping technique using non-linear curve fitting

The aim of this study is to develop a new simple method for analyzing one-dimensional transcranial magnetic stimulation (TMS) mapping studies in humans. Motor evoked potentials (MEP) were recorded from the abductor pollicis brevis (APB) muscle during stimulation at nine different positions on the scalp along a line passing through the APB hot spot and the vertex. Non-linear curve fitting according to the Levenberg-Marquardt algorithm was performed on the averaged amplitude values obtained at all points to find the best-fitting symmetrical and asymmetrical peak functions. Several peak functions could be fitted to the experimental data. Across all subjects, a symmetric, bell-shaped curve, the complementary error function (erfc) gave the best results. This function is characterized by three parameters giving its amplitude, position, and width. None of the mathematical functions tested with less or more than three parameters fitted better. The amplitude and position parameters of the erfc were highly correlated with the amplitude at the hot spot and with the location of the center of gravity of the TMS curve. In conclusion, non-linear curve fitting is an accurate method for the mathematical characterization of one-dimensional TMS curves. This is the first method that provides information on amplitude, position and width simultaneously.

[Medium-term results after m. vastus medialis obliquus-plasty for lateral patellar dislocation]

Progressive retropatellar arthrosis is often seen in dated rigid distal realignment (i.e. osteotomy of tuberositas) at long-term follow-ups. Therefore, operations for lateral dislocation of the patella are still discussed controversially. Dynamic, proximal realignments seem to have lower rates of arthrosis but higher rates of redislocation. Recently, in anatomic and biomechanic studies, the m. vastus medialis obliquus (vmo) was found to be one of the most important proximal restraints to lateral dislocation of the patella.A total of 28 patients (mean age 21.5 years) were treated between 1994 and 2003 with a plasty of the vmo for lateral patellar dislocation. The technique was performed for most etiologies of femoropatellar instability.For this proximal soft tissue technique, the muscle tendon is detached from its patellar insertion. Subsequently, the tendon is reinserted at the patella 10-15 mm more distally and fixed with Mitek anchors. Full weight bearing in extension is possible immediately after surgery. An active vastus medialis training is started after 6 weeks.Of the patients, 27 were evaluated clinically and radiologically in 2004 (a mean of 5 years postoperatively). A total of 83% of the patients estimated the result to be good or excellent, 10% were satisfied and 7% were discontent. The mean Lysholm-Knee-Score was 83.1 points. Two patients suffered a patella redislocation (7%). A statistically significant improvement of the congruence angle was noted in the radiographs, even in medium-term controls. In 89% of the cases no or only little retropatellar arthrosis was observed. These 5 year results are comparable to those of other techniques for distal or proximal realignments. The rate of redislocation was below average. Compared to the rate of retropatellar arthrosis in long-term results of rigid distal realignment, our patients demonstrated a relative low rate after 5 years. We attribute this to the minimal interference in physiological joint mechanics and to the restored anatomy. In terms of future long-term results, our findings are promising. The idea of a proximal dynamic stabilization and the causal operative approach at the origin of pathology using vmo-plasty was confirmed in recent anatomic and biomechanic studies. Over or under correction of soft tissues could be adapted. More rigid techniques of distal realignment do not allow an adaptation to this extent and can lead to prearthrotic hyperpression in the medial femoropatellar and femorotibial joints.

Maximum intensity projection of cranial computed tomography data for dental identification

Dental radiographs play the major role in the identification of victims in mass casualties besides DNA. Under circumstances such as those caused by the recent tsunami in Asia, it is nearly impossible to document the entire dentition using conventional x-rays as it would be too time consuming. Multislice computed tomography can be used to scan the dentition of a deceased within minutes, and the postprocessing software allows visualization of the data adapted to every possible antemortem x-ray for identification. We introduce the maximum intensity projection of cranial computed tomography data for the purpose of dental identification exemplarily in a case of a burned corpse. As transportable CT scanners already exist, these could be used to support the disaster victim identification teams in the field.

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex affects divided attention immediately after cessation of stimulation

Transcranial magnetic stimulation has evolved into a powerful neuroscientific tool allowing to interfere transiently with specific brain functions. In addition, repetitive TMS (rTMS) has long-term effects (e.g. on mood), probably mediated by neurochemical alterations. While long-term safety of rTMS with regard to cognitive functioning is well established from trials exploring its therapeutic efficacy, little is known on whether rTMS can induce changes in cognitive functioning in a time window ranging from minutes to hours, a time in which neurochemical effects correlated with stimulation have been demonstrated. This study examined effects of rTMS on three measures of executive function in healthy subjects who received one single rTMS session (40 trains of 2 s duration 20 Hz stimuli) at the left dorsolateral prefrontal cortex (DLPFC). Compared to a sham condition one week apart, divided attention performance was significantly impaired about 30-60 min after rTMS, while Stroop-interference and performance in the Wisconsin Card Sorting Test was unaffected after rTMS. Repetitive TMS of the left DLPFC, at stimulation parameters used in therapeutic studies, does not lead to a clinically relevant impairment of executive function after stimulation. However, the significant effect on divided attention suggests that cognitive effects of rTMS are not limited to the of acute stimulation, and may possibly reflect known neurochemical alterations induced by rTMS. Sensitive cognitive measures may be useful to trace those short-term effects of rTMS non-invasively in humans.

Computer-assisted, fluoroscopy-based ventral spondylodesis of thoracolumbar fractures

OBJECTIVE: To design and evaluate a novel computer-assisted, fluoroscopy-based planning and navigation system for minimally invasive ventral spondylodesis of thoracolumbar fractures. MATERIALS AND METHODS: Instruments and an image intensifier are tracked with the SurgiGATE navigation system (Praxim-Medivision). Two fluoroscopic images, one acquired from anterior-posterior (AP) direction and the other from lateral-medial (LM) direction, are used for the complete procedure of planning and navigation. Both of them are calibrated with a custom-made software to recover their projection geometry and to co-register them to a common patient reference coordinate system, which is established by attaching an opto-electronically trackable dynamic reference base (DRB) on the operated vertebra. A bi-planar landmark reconstruction method is used to acquire deep-seated anatomical landmarks such that an intraoperative planning of graft bed can be interactively done. Finally, surgical actions such as the placement of the stabilization devices and the formation of the graft bed using a custom-made chisel are visualized to the surgeon by superimposing virtual instrument representations onto the acquired images. The distance between the instrument tip and each wall of the planned graft bed are calculated on the fly and presented to the surgeon so that the surgeon could formalize the graft bed exactly according to his/her plan. RESULTS: Laboratory studies on phantom and on 27 plastic vertebras demonstrate the high precision of the proposed navigation system. Compared with CT-based measurement, a mean error of 1.0 mm with a standard deviation of 0.1 mm was found. CONCLUSIONS: The proposed computer assisted, fluoroscopy-based planning and navigation system promises to increase the accuracy and reliability of minimally invasive ventral spondylodesis of thoracolumbar fractures.

Reorganization of CA3 area of the mouse hippocampus after pilocarpine induced temporal lobe epilepsy with special reference to the CA3-septum pathway

We showed that when CA3 pyramidal neurons in the caudal 80% of the dorsal hippocampus had almost disappeared completely, the efferent pathway of CA3 was rarely detectable. We used the mouse pilocarpine model of temporal lobe epilepsy (TLE), and injected iontophoretically the anterograde tracer phaseolus vulgaris leucoagglutinin (PHA-L) into gliotic CA3, medial septum and the nucleus of diagonal band of Broca, median raphe, and lateral supramammillary nuclei, or the retrograde tracer cholera toxin B subunit (CTB) into gliotic CA3 area of hippocampus. In the afferent pathway, the number of neurons projecting to CA3 from medial septum and the nucleus of diagonal band of Broca, median raphe, and lateral supramammillary nuclei increased significantly. In the hippocampus, where CA3 pyramidal neurons were partially lost, calbindin, calretinin, parvalbumin immunopositive back-projection neurons from CA1-CA3 area were observed. Sprouting of Schaffer collaterals with increased number of large boutons in both sides of CA1 area, particularly in the stratum pyramidale, was found. When CA3 pyramidal neurons in caudal 80% of the dorsal hippocampus have almost disappeared completely, surviving CA3 neurons in the rostral 20% of the dorsal hippocampus may play an important role in transmitting hyperactivity of granule cells to surviving CA1 neurons or to dorsal part of the lateral septum. We concluded that reorganization of CA3 area with its downstream or upstream nuclei may be involved in the occurrence of epilepsy.

Association of a large lateral extension of the acromion with rotator cuff tears

BACKGROUND: Factors predisposing to tearing of the rotator cuff are poorly understood. We have observed that the acromion of patients with a rotator cuff tear very often appears large on anteroposterior radiographs or during surgery. The purpose of this study was to quantify the lateral extension of the acromion in patients with a full-thickness rotator cuff tear and in patients with an intact rotator cuff. METHODS: The lateral extension of the acromion was assessed on true anteroposterior radiographs made with the arm in neutral rotation. The distance from the glenoid plane to the lateral border of the acromion was divided by the distance from the glenoid plane to the lateral aspect of the humeral head to calculate the acromion index. This index was determined in a group of 102 patients (average age, 65.0 years) with a proven full-thickness rotator cuff tear, in an age and gender-matched group of forty-seven patients (average age, 63.7 years) with osteoarthritis of the shoulder and an intact rotator cuff, and in an age and gender-matched control group of seventy volunteers (average age, 64.4 years) with an intact rotator cuff as demonstrated by ultrasonography. RESULTS: The average acromion index (and standard deviation) was 0.73 +/- 0.06 in the shoulders with a full-thickness tear, 0.60 +/- 0.08 in those with osteoarthritis and an intact rotator cuff, and 0.64 +/- 0.06 in the asymptomatic, normal shoulders with an intact rotator cuff. The difference between the index in the shoulders with a full-thickness supraspinatus tear and the index in those with an intact rotator cuff was highly significant (p < 0.0001). CONCLUSIONS: A large lateral extension of the acromion appears to be associated with full-thickness tearing of the rotator cuff.

Comparison of different radiography systems in an experimental study for detection of forearm fractures and evaluation of the Müller-AO and Frykman classification for distal radius fractures

OBJECTIVES: We sought to compare the diagnostic performance of screen-film radiography, storage-phosphor radiography, and a flat-panel detector system in detecting forearm fractures and to classify distal radius fractures according to the Müller-AO and Frykman classifications compared with the true extent, depicted by anatomic preparation. MATERIALS AND METHODS: A total of 71 cadaver arms were fractured in a material testing machine creating different fractures of the radius and ulna as well as of the carpal bones. Radiographs of the complete forearm were evaluated by 3 radiologists, and anatomic preparation was used as standard of reference in a receiver operating curve analysis. RESULTS: The highest diagnostic performance was obtained for the detection of distal radius fractures with area under the receiver operating curve (AUC) values of 0.959 for screen-film radiography, 0.966 for storage-phosphor radiography, and 0.971 for the flat-panel detector system (P > 0.05). Exact classification was slightly better for the Frykman (kappa values of 0.457-0.478) compared with the Müller-AO classification (kappa values of 0.404-0.447), but agreement can be considered as moderate for both classifications. CONCLUSIONS: The 3 imaging systems showed a comparable diagnostic performance in detecting forearm fractures. A high diagnostic performance was demonstrated for distal radius fractures and conventional radiography can be routinely performed for fracture detection. However, compared with anatomic preparation, depiction of the true extent of distal radius fractures was limited and the severity of distal radius fractures tends to be underestimated.

Time course of blood oxygenation level-dependent signal response after theta burst transcranial magnetic stimulation of the frontal eye field

The aim of the current study was to examine the effect of theta burst repetitive transcranial magnetic stimulation (rTMS) on the blood oxygenation level-dependent (BOLD) activation during repeated functional magnetic resonance imaging (fMRI) measurements. Theta burst rTMS was applied over the right frontal eye field in seven healthy subjects. Subsequently, repeated fMRI measurements were performed during a saccade-fixation task (block design) 5, 20, 35, and 60 min after stimulation. We found that theta burst rTMS induced a strong and long-lasting decrease of the BOLD signal response of the stimulated frontal eye field at 20 and 35 min. Furthermore, less pronounced alterations of the BOLD signal response with different dynamics were found for remote oculomotor areas such as the left frontal eye field, the pre-supplementary eye field, the supplementary eye field, and both parietal eye fields. Recovery of the BOLD signal changes in the anterior remote areas started earlier than in the posterior remote areas. These results show that a) the major inhibitory impact of theta burst rTMS occurs directly in the stimulated area itself, and that b) a lower effect on remote, oculomotor areas can be induced.