Clinical evaluation of the Sorin Xtra(R) Autotransfusion System.

The performance of the Sorin Xtra® Autotransfusion System (ATS) was studied in 62 patients undergoing coronary artery bypass grafting. Blood was collected intraoperatively and washed using three different wash sets in 4 groups. Both collected and washed blood were analysed for hemoglobin levels and hematocrit, concentrations of proteins, albumin, heparin and plasma free hemoglobin (PFH) were determined, erythrocytes, platelets and leukocytes were counted. Hematocrit measurements of the Xtra® were compared with laboratory measurements to study the accuracy of the Xtra® hematocrit sensor. In addition, the red blood cell recovery rate and elimination rates were calculated to evaluate the clinical performance of the Xtra®. The Xtra® ATS produced a volume of concentrated red blood cells with an average hematocrit from 58% to 63%, depending on the size of the bowl and the chosen default program. In all bowl sizes and programs, the Xtra® Hct-out measurement underestimated the CELL-DYN measurement by approximately 15%. The calculated recovery rates for red blood cells (RBC) in the 4 groups ranged from 86.7% to 91.6%. Elimination rates were calculated in each group for proteins (96.8-99.2%), albumin (96.4-98.7%), plasma free hemoglobin (83.6-91.2%), heparin (98.8-99.9%), platelets (82.4-94.3%) and white blood cells (28.6-42.3%). The Xtra® ATS can be appealing for its performance by producing high hematocrit levels in the washed RBC volume, while keeping RBC recovery rate at the same high level (≈ 90%) as in its predecessor, the Electa® Autotransfusion System.

The outcome of proximal fifth metatarsal fractures: redefining treatment strategies.

BACKGROUND: To optimize the treatment strategy and reduce treatment costs of proximal fifth metatarsal fractures, clinical and patient-reported outcome, and its determinants were addressed. METHODS: A retrospective adult cohort study including 152 proximal fifth metatarsal fractures: 121 nonoperatively and 31 operatively treated. In the operative group, 21 were zone 1 and 10 zone 2 fractures. Median follow-up was 37.5 (IQR 20.8-52.3) months with a minimal follow-up of 6 months. Twenty-three demographic, fracture, and treatment characteristics were assessed as well as the healthcare costs. Outcome was assessed using the patient files, anterior-posterior and oblique X-rays, foot function index (FFI), visual analog score (VAS), and SF-36 questionnaires. RESULTS: The median FFI, physical SF-36, and VAS scores did not significantly differ between nonoperatively and operatively treated patients. The FFI and physical SF-36 were predominantly affected by a history of mobility impairment and pre-existent cardiovascular diseases, whereas mental SF-36 correlated significantly with higher ASA-score. Overall complication rate was 5.9% (4.1 vs. 12.9%; p = 0.065, nonoperative vs. operative, respectively). Nonunion was recorded in only one (nonoperatively) treated patient. The total healthcare costs for operative treatment were 4.2 times higher compared to nonoperative treatment (€1960 vs. €463 per patient, respectively). CONCLUSION: Overall, the clinical and patient-reported outcome was good. The foot function and quality of life were mainly affected by comorbidity, rather than fracture and treatment-related variables. Although nonoperatively treated patients indicated decreased mental quality of life, our study indicates that proximal fifth metatarsal fractures can safely be treated nonoperatively without the risk of nonunion, with fewer complications and lower healthcare costs. LEVEL OF EVIDENCE: 3.

Persistent STAT5 activation in myeloid neoplasms recruits p53 into gene regulation.

STAT (Signal Transducer and Activator of Transcription) transcription factors are constitutively activated in most hematopoietic cancers. We previously identified a target gene, LPP/miR-28 (LIM domain containing preferred translocation partner in lipoma), induced by constitutive activation of STAT5, but not by transient cytokine-activated STAT5. miR-28 exerts negative effects on thrombopoietin receptor signaling and platelet formation. Here, we demonstrate that, in transformed hematopoietic cells, STAT5 and p53 must be synergistically bound to chromatin for induction of LPP/miR-28 transcription. Genome-wide association studies show that both STAT5 and p53 are co-localized on the chromatin at 463 genomic positions in proximal promoters. Chromatin binding of p53 is dependent on persistent STAT5 activation at these proximal promoters. The transcriptional activity of selected promoters bound by STAT5 and p53 was significantly changed upon STAT5 or p53 inhibition. Abnormal expression of several STAT5-p53 target genes (LEP, ATP5J, GTF2A2, VEGFC, NPY1R and NPY5R) is frequently detected in platelets of myeloproliferative neoplasm (MPN) patients, but not in platelets from healthy controls. In conclusion, persistently active STAT5 can recruit normal p53, like in the case of MPN cells, but also p53 mutants, such as p53 M133K in human erythroleukemia cells, leading to pathologic gene expression that differs from canonical STAT5 or p53 transcriptional programs.

Myasthenic syndrome caused by direct effect of chloroquine on neuromuscular junction.

Chloroquine induced a myasthenic syndrome in a patient taking the drug for presumable reticular erythematous mucinosis. Clinical features and results of single-fiber electromyography were typical for a failure of neuromuscular transmission, while peripheral nerves and muscles were intact on clinical, biochemical, electrophysiologic, and pathologic investigation. The time course of the clinical and electrophysiologic findings during provocation with chloroquine and the absence of autoantibodies indicate that the syndrome was due to a direct effect of the drug on the neuromuscular junction. While not taking chloroquine, the patient showed a decremental response on a modified double-step nerve stimulation test and a mean consecutive difference on single-fiber electromyography that was at the upper limit of normal, indicating a subclinical impairment of neuromuscular transmission. These findings can explain the apparent rarity of the syndrome described, as a direct effect of chloroquine on the neuromuscular junction may only have clinical relevance in patients with a reduced neuromuscular safety factor.

Transfer factor therapy in multiple sclerosis: a three-year prospective double-blind clinical trial.

One hundred five patients with MS were divided into three groups matched for age, sex, and disability, and treated with either placebo, transfer factor prepared from leukocytes of random donors, or transfer factor from leukocytes of family members living with the patients. There were no differences in the three treatment groups for changes in disability, activities of daily living, or evoked potentials. Eighteen months of transfer factor therapy had no effect on gamma-interferon production or natural killer cell activities.

Suppression of C-fibre discharges upon repeated heat stimulation may explain characteristics of concomitant pain sensations.

Nociceptors with unmyelinated axons were recorded from the superficial radial nerves of 7 volunteers. A sequence of uniform radiant heat stimuli of 18 s duration, starting from an individually adjusted adapting temperature were used to raise the skin surface temperature by 6 degrees C to a painful level (41-43 degrees C). These stimuli followed each other at 3 different interstimulus intervals of 35 s, 70 s and 105 s, occurring in a random order. The subjects were asked to track the time course of the stimulus-evoked sensation by manipulating the length of a light bar. Adaptation and stimulus temperatures were chosen to induce sensations of heat and/or pain. All nociceptors studied responded to these stimuli with a phasic response of 3-5 s duration, often followed by a low frequency tonic discharge, lasting as long as the stimulus. No discharges were seen in interstimulus periods. Discharge rates during the phasic responses were linearly related to interval duration, whereas tonic discharges were not influenced by the preceding interval. In parallel readings of pain responses were lower up to the 10th second of the stimulus after short rather than after long intervals. These results indicate that the suppression of C-fibre nociceptor discharges during repetitive stimulation may explain concomitant reductions in the magnitude of human pain sensations.

Magnesium deficiency as a cause of acute intractable seizures.

Clinical and experimental investigations have shown that magnesium depletion causes a marked irritability of the nervous system, eventually resulting in epileptic seizures. Although magnesium deficiency as a cause of epilepsy is uncommon, its recognition and correction may prove life-saving. Two case reports are presented which emphasize the importance of recognizing hypomagnesaemia in patients with acute intractable seizures.

Latencies of chemically evoked discharges in human cutaneous nociceptors and of the concurrent subjective sensations.

Percutaneous recordings from single nociceptive A delta- and C-fibers have been performed from the superficial radial nerves of conscious human subjects. Nociceptors were tested with a chemical irritant substance, which induced a burning sensation when applied to the intact skin. A comparison of the onset of spike discharges in nociceptors and the onset of the subjective burning sensation indicated that under the conditions of our experiments summation of input from nociceptors is needed in order to induce pain sensations. In particular, our results indicate spatial summation.

Pathological findings in a patient with amyotrophic lateral sclerosis and multifocal motor neuropathy with conduction block.

We studied a 53-year-old woman with progressive weakness of the left arm, gradually spreading to the other limbs. Neurological examination revealed a motor neuron syndrome with paresis, fasciculations and atrophy. Electrophysiological studies showed multiple motor conduction blocks. The anti-GM1 IgM titer was elevated. The patient was thought to have a multifocal motor neuropathy. Despite intravenous cyclophosphamide treatment, however, she died with respiratory insufficiency. On postmortem examination, the brachial plexus showed patches of demyelination underlying different areas of motor conduction block. The spinal cord, however, revealed severe neuronal loss in the ventral horn and axonal loss in the corticospinal tract, indicative of amyotrophic lateral sclerosis. Demyelination of peripheral nerves could have been responsible for the other conduction blocks in this patient. The prominent degeneration of motor neurons, however, must also have played a role in the clinical picture. Some patients with the syndrome of a multifocal motor neuropathy may have MND rather than, or in addition to, a demyelinating peripheral motor neuropathy.

Histochemical changes of substance P, FRAP, serotonin and succinic dehydrogenase in the spinal cord of rats with adjuvant arthritis.

Various histochemical changes were found in spinal segments L4-L5 of rats with adjuvant arthritis, predominantly 30 days after inoculation. A slight to marked increase of substance P immunoreactivity occurred in laminae I, II and X. FRAP activity was enhanced in lamina II. Serotonin immunoreactivity was heavier in laminae I, VIII and IX in a few animals. The intensity of the histoenzymological reaction for succinic dehydrogenase increased in certain laminae VIII and X neurons. At day 15 of the disease the increase of substance P and FRAP activities was chiefly restricted to the medial portion of the superficial dorsal horn. There was a significant positive correlation between the scratching behaviour of arthritic rats and the substance P immunoreactivity in laminae X and I. If one accepts that scratching is pain-related, the data are consistent with a possible role of substance P in the chronic pain associated with adjuvant arthritis. They leave undetermined the significance of the other histochemical changes.

Sensations and trigeminal somatosensory-evoked potentials elicited by electrical stimulation of endosseous oral implants in humans.

The perception of bipolar electrical stimuli through implants was studied. The stimuli were delivered to permucosal oral endosseous implants in 15 individuals, who then reported tapping to beating sensations. In 10 out of the 15, these stimuli evoked clearly distinguishable potentials in the averaged electroencephalograms. The most prominent scalp potential was a positive wave with a latency between 18 and 25 ms, often preceded by a negative wave with a latency around 12-17 ms. In contrast, when a motor response was elicited by stimulation of the lip, a shorter latency wave around 8-11 ms was found additionally, indicating that the former-mentioned waves represent a true sensory response and not an artefact of myogenous origin. Furthermore, topical anaesthesia of the gingiva surrounding the implants in six individuals had little effect on the sensory responses. This evidence excluded peri-implant mucosal innervation as the origin of the perception and of the somatosensory-evoked waves elicited by the electrical stimulation of the oral implants. To the best of our knowledge, for the first time a sensation (osseoperception) has been elicited by electrical stimulation of endosseous oral implants and correlated with simultaneously recorded trigeminal somatosensory-evoked potentials (TSEPs).

Trigeminal somatosensory evoked potentials in humans.

The recording of somatosensory evoked potentials (SEPs) is a non-invasive routine clinical testing procedure in neurology. For trigeminal nerve stimulation, however, SEPs have not received a widespread clinical attention. A variety of protocols and procedures have been used to record trigeminal SEPs (TSEPs). Differences encountered include the stimulation mode, site and frequency, the recording electrode position and data acquisition parameters. This has resulted in a diversity of recorded TSEP signals, making comparisons almost impossible. The general picture shows a number of short latency waves (within 3 ms) of peripheral origin, followed by at least two longer latency waves (12-15 ms and 19-22 ms). Furthermore, potential waves with a very long latency (> 100 ms) follow when the response is produced by painful stimulation. The origin of the long and very long latency waves is still a matter of debate. In order to allow reliable data interpretation and comparisons between the outcome of different studies, a standardized protocol should be applied for TSEP recordings. By providing an overview, this paper aims to mark a step forward in the harmonization of TSEP protocols with respect to the neural processes of interest. Further studies should also encounter the potential application of other neuroimaging techniques, such as functional magnetic resonance imaging or positron emission tomography, preferably in combination with TSEP recordings.

A hypothetical immunemediated unifying mechanism for the Holmes-Adie syndrome.

The Holmes-Adie syndrome consists of pupillotonia, arreflexia and autonomic dysfunction. Some explanations for these different symptoms have been attempted, centred upon neuropathological and electrophysiological findings. A hypothetical immunemediated mechanism, as in the Guillain Barré syndrome, is presented in this paper for explaining the three chief symptoms of the syndrome.

Peripheral cutaneous nerve distribution to the fingers.

Both sensory distribution charts and the unaffected side, are used as reference points in the assessment of cutaneous innervation. Sensory nerve conduction studies, in particular, often use comparison between sides. However, remarkable differences can be found between various sensory innervation maps, and no evidence was found in the literature for the assumption that the pattern of cutaneous sensory distribution of the peripheral nerves between the left and right limbs is symmetrical. The purpose of this study was to investigate variations in the sensory innervation of the fingers by means of a neurophysiological method, and to compare the results for the left and right hands. The subjects of this study were 31 young women. Percutaneous peripheral nerve stimulation was performed on the four nerve branches providing sensory innervation to the fingers, and action potentials were sought from the fingers by use of annular surface electrodes. Variations in the cutaneous innervation of the fingers between individuals often occurred and were found more frequently on the dorsal than the palmar aspect. The distribution of sensory innervation may even differ markedly between hands in the same individual. The cutaneous innervation of all peripheral nerves supplying the fingers may differ from the innervation patterns described in the various distribution charts. Prudence is called for when applying sensory distribution charts as absolute references for the assessment of cutaneous sensation in patients. Caution should also be applied when comparing one hand with the other when assessing the cutaneous innervation of the fingers.

Long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis: a longitudinal study.

OBJECTIVE: To describe long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis (RA). METHODS: Longitudinal data over a period of 11 years were collected from 882 patients with RA at study inclusion. Patient-reported outcomes were collected in 1997, 1998, 1999, 2002, and 2008. Physical functioning was measured with the Health Assessment Questionnaire and the physical component summary score of the Short Form 36 health survey. Somatic comorbidity was measured by a questionnaire including 12 chronic diseases. Comorbid depression was measured with the Center for Epidemiologic Studies Depression Scale. We distinguished 4 groups of patients based on comorbidity at baseline. RESULTS: Seventy-two percent of the patients at baseline were women. The mean ± SD age was 59.3 ± 14.8 years and the median disease duration was 5.0 years (interquartile range 2.0-14.0 years). For the total group of patients with RA, physical functioning improved over time. Patients with somatic comorbidity, comorbid depression, or both demonstrated worse physical functioning than patients without comorbidity at all data collection points. Both groups with comorbid depression had the lowest scores. Only patients with both somatic comorbidity and comorbid depression showed significantly less improvement in physical functioning over time. CONCLUSION: Both somatic comorbidity and comorbid depression were negatively associated with physical functioning during an 11-year followup period. Furthermore, their combination seems to be especially detrimental to physical functioning over time. These results emphasize the need to take somatic comorbidity and comorbid depression into account in the screening and treatment of patients with RA.