Biomechanical and energetic effects of a stance-control orthotic knee joint

Users of traditional knee-ankle-foot orthoses (KAFOs) walk with either locked or unlocked knee joints depending on the level of stability required. Some users may benefit from new stance-control KAFOs that prevent stance-phase knee flexion but allow swing-phase flexion. We collected data from nine nondisabled adults who walked with KAFOs that incorporated the Horton Stance-Control Orthotic Knee Joint (SCOKJ) in the locked, unlocked, and auto (which provides knee stability during stance phase and knee flexion during swing phase) modes to investigate the biomechanical and energetic effects of stance-control orthoses. Studying nondisabled subjects allowed us to analyze the effects of stance-control orthoses in a homogenous population. In general, gait kinematics for the auto and unlocked modes were more similar than for the auto and locked modes. Despite the elimination of hip hiking in the auto mode, oxygen cost was not different between the auto and locked modes (p > 0.99). The SCOKJ allowed our nondisabled subjects to walk with a more normal gait pattern; however, future research should explore the effect of stance-control orthoses on persons with gait pathology.     

Perfusionists in the world of tissue engineering--a quick and easy method for safe isolation of huge quantities of porcine cardiomyocytes

Isolation of huge quantities of primary cells from whole organs like the heart becomes increasingly important, especially for the emerging research field of tissue engineering and regenerative medicine. This study deals with the isolation of pig cardiomyocytes, in contrast to the standard mouse or rat models, because we aimed to draw attention to the species, which are genetically more closely related to the human organism. The bigger operative and veterinary expenditure of the pig-heart model can only be justified by a technique that supplies a big amount of qualitative high-grade cardiomyocytes. In our model, the quality is guaranteed by protection of the heart, already in situ, by a cardioplegia and a careful application of collagenase to soften the tissue. The construction of a new apparatus which includes enormous costs was not necessary, since the perfusion equipment was realized from two commercially available HLMsets, which were modified and connected to each other. Our model makes it possible to rinse the whole myocardium, which leads to a better output than models that only prepare a part of the myocardium around a coronary artery. The careful harvesting of high-grade cardiomyocytes is an important source of successful cell cultures to be used for numerous experimental applications, may reduce animal experiments and, additionally, represents a chance for perfusionists to become an important partner in interdisciplinary research projects.     

The selective poly(ADP)ribose-polymerase 1 inhibitor INO1001 reduces spinal cord injury during porcine aortic cross-clamping-induced ischemia/reperfusion injury

OBJECTIVE: It is well-established that poly(ADP)ribose-polymerase (PARP) assumes major importance during ischemic brain damage, and the selective PARP-1 inhibitor PJ34 reduced spinal cord damage in murine aortic occlusion-induced ischemia/reperfusion injury. We investigated the effect of the PARP-1 inhibitor INO1001 on aortic-occlusion-related porcine spinal cord injury. DESIGN AND SETTING: Prospective, randomized, controlled experimental study in an animal laboratory. PATIENTS AND PARTICIPANTS: Ten anesthetized, mechanically ventilated, and instrumented pigs. INTERVENTIONS: Animals underwent 45 min of thoracic aortic cross-clamping after receiving vehicle (n=5) or intravenous INO1001 (n=5, total dose 4 mg/kg administered both before clamping and during reperfusion). During reperfusion continuous intravenous norepinephrine was incrementally adjusted to maintain blood pressure at or above 80% of the preclamping level. Plasma INO1001 levels were analyzed by HPLC. After 4[Symbol: see text]h of reperfusion spinal cord biopsy samples were analyzed for neuronal damage (hematoxyline-eosine and Nissl staining), expression of the cyclin-dependent kinase inhibitor genes p21 and p27 (immunohistochemistry), and apoptosis (terminal deoxynucleotidyl transferase mediated nick end labeling assay). MEASUREMENTS AND RESULTS: Plasma INO1001 levels were 0.8-2.3 and 0.30-0.76 mM before and after clamping, respectively. While 3-5% of the spinal cord neurons were irreversibly damaged in the INO1001 animals, the neuronal cell injury was three times higher in the control group. Neither p21 and p27 expression nor apoptosis showed any intergroup difference. CONCLUSIONS: The selective PARP-1 inhibitor INO1001 markedly reduced aortic occlusion-induced spinal cord injury. Given the close correlation reported in the literature between morphological damage and impaired spinal cord function, INO1001 may improve spinal cord recovery after thoracic aortic cross-clamping.     

Hypnosis and Local Anesthesia for Dental Pain Relief—Alternative or Adjunct Therapy?—A Randomized,Clinical-Experimental Crossover Study

This prospective randomized clinical crossover trial was designed to compare hypnosis and local anesthesia for experimental dental pain relief. Pain thresholds of the dental pulp were determined. A targeted standardized pain stimulus was applied and rated on the Visual Analogue Scale (0–10). The pain threshold was lower under hypnosis (58.3 ± 17.3, p < .001), maximal (80.0) under local anesthesia. The pain stimulus was scored higher under hypnosis (3.9 ± 3.8) than with local anesthesia (0.0, p < .001). Local anesthesia was superior to hypnosis and is a safe and effective method for pain relief in dentistry. Hypnosis seems to produce similar effects observed under sedation. It can be used in addition to local anesthesia and in individual cases as an alternative for pain control in dentistry.     

Interaction Between Aminoglycoside Uptake and Ribosomal Resistance Mutations

Mutants resistant to the 2-deoxystreptamine aminoglycosides hygromycin B and gentamicin were analyzed biochemically and genetically. In hygromycin B-resistant strains, ribosomal alterations were not detectable by electrophoretic or genetic experiments. Rather, as was demonstrated for one strain in detail, resistance to this drug seems to be the consequence of several mutations, each impairing drug accumulation, namely of a deletion of a gene close to the proC marker which potentiates the effect of a second mutation in the unc gene cluster. Three mutants resistant to gentamicin which were previously demonstrated to harbor an altered ribosomal protein, L6, were shown in addition to contain unc. Both the unc and the ribosomal mutation greatly impair the drug accumulation ability of the mutants. Further evidence for the direct effect of ribosomal mutations on the uptake of aminoglycosides was obtained with strains that possess ribosomes with increased affinity for dihydrostreptomycin. Dihydrostreptomycin transport by these cells is greatly stimulated; thus, the hypersensitivity of these mutants is caused by increased binding affinity for dihydrostreptomycin and its secondary effect on the uptake process. Experiments were also performed on the biochemical basis of the third phase of aminoglycoside transport (acceleration phase). The condition for its onset is that ribosomes are active in protein synthesis irrespective of whether the proteins synthesized are functional. This, and the failure to observe the synthesis of new proteins upon the addition of aminoglycosides, do not support the view of autoinduction of a cognate or related transport system.     

Optimizing bag-valve-mask ventilation with a new mouth-to-bag resuscitator

When ventilating an unintubated patient with a self-inflating bag, high peak inspiratory flow rates may result in high peak airway pressure with subsequent stomach inflation; this may occur frequently when rescuers without daily experience in bag-valve-mask ventilation need to perform advanced airway management. The purpose of this study was to assess the effects of a newly developed self-inflating bag (mouth-to-bag resuscitator; Ambu, Glostrup, Denmark) that limits peak inspiratory flow. A bench model simulating a patient with an unintubated airway was used, consisting of a face mask, manikin head, training lung (lung compliance, 100 ml/0.098 kPa (100 ml/cm H(2)O)); airway resistance, 0.39 kPa/l per second (4 cm H(2)O/l/s), oesophagus (LESP, 1.96 kPa (20 cm H(2)O)) and simulated stomach. Twenty nurses were randomised to ventilate the manikin for 1 min (respiratory rate: 12 per minute) with either a standard self-inflating bag or the mouth-to-bag resuscitator, which requires the rescuer to blow up a single-use balloon inside the self-inflating bag, which in turns displaces air towards the patient. When supplemental oxygen is added, ventilation with up to 100% oxygen may be obtained, since expired air is only used as the driving gas. The mouth-to-bag resuscitator therefore allows two instead of one hand sealing the mask on the patient's face. The volunteers were blinded to the experimental design of the model until completion of the experimental protocol. The mouth-to-bag resuscitator versus standard self-inflating bag resulted in significantly (P<0.05) higher mean+/-S.D. mask tidal volumes (1048+/-161 vs. 785+/-174 ml) and lung tidal volumes (911+/-148 vs. 678+/-157 ml), longer inspiratory times (1.7+/-0.4 vs. 1.4+/-0.4 s), but significantly lower peak inspiratory flow rates (50+/-9 vs. 62+/-13 l/min) and mask leakage (10+/-4 vs. 15+/-9%); peak inspiratory pressure (17+/-2 vs. 17+/-2 cm H(2)O) and stomach tidal volumes (16+/-30 vs. 18+/-35 ml) were comparable. In conclusion, employing the mouth-to-bag resuscitator during simulated ventilation of an unintubated patient in respiratory arrest significantly decreased inspiratory flow rate and improved lung tidal volumes, while decreasing mask leakage.     

Early liver retransplantation in adults

Up to 23% of liver allografts fail post‐transplant. Retransplantation is only the recourse but remains controversial due to inferior outcomes. The objective of our study was to identify high‐risk periods for retransplantation and then compare survival outcomes and risk factors. We performed an analysis of United Network for Organ Sharing (UNOS) data for all adult liver recipients from 2002 through 2011. We analyzed the records of 49 288 recipients; of those, 2714 (5.5%) recipients were retransplanted. Our analysis included multivariate regression with the outcome of retransplantation. The highest retransplantation rates were within the first week (19% of all retransplantation, day 0–7), month (20%, day 8–30), and year (33%, day 31–365). Only retransplantation within the first year (day 0–365) had below standard outcomes. The most significant risk factors were as follows: within the first week, cold ischemia time >16 h [odds ratio (OR) 3.6]; within the first month, use of split allografts (OR 2.9); and within the first year, use of a liver donated after cardiac death (OR 4.9). Each of the three high‐risk periods within the first year had distinct causes of graft failure, risk factors for retransplantation, and survival rates after retransplantation.     

Physiological effects of cigarette smoking in the limbic system revealed by 3 tesla magnetic resonance spectroscopy

Several studies and recent models of effects of nicotine, the main addictive and psychoactive component in tobacco, point to action of the drug on the limbic system during maintenance of addiction, either direct or indirect via projections from the ventral tegmental area. The objective of this study was to demonstrate physiological effects of cigarette smoking on the hippocampus and the grey matter of the dorsal anterior cingulate cortex in the human brain with regard to addiction and withdrawal. This aim was achieved by group comparisons of results of magnetic resonance spectroscopy between non-smokers, smokers and smokers during withdrawal. 12 smokers and 12 non-smokers were measured with single voxel proton magnetic resonance spectroscopy for total N-acetyl aspartate, glutamate and glutamine, choline-containing compounds, myo-inositol and total creatine in the right and the left hippocampus and in the right and the left dorsal anterior cingulate cortex. Smokers were examined twice, first during regular cigarette smoking and second on the third day of nicotine withdrawal. The ratios to total creatine were used for better reliability. In our study, Glx/tCr was significantly increased and tCho/tCr was significantly decreased in the left cingulate cortex in smokers compared to non-smokers (p = 0.01, both). Six out of seven smokers showed normalization of the Glx/tCr in the left cingulate cortex during withdrawal. Although these results are preliminary due to the small sample size, our results confirm the assumption that cigarette smoking interferes directly or indirectly with the glutamate circuit in the dorsal anterior cingulate cortex.     

Evaluation of ocular surface and tear film function following modified Hughes tarsoconjunctival flap procedure

Purpose: To evaluate ocular surface characteristics and tear film function following modified Hughes flap for eyelid reconstruction. Methods: This is an institutional study including 18 patients (6 male, 12 female) who underwent a tarsoconjunctival flap for reconstructing the lower eyelid’s posterior lamella in one eye between 2005 and 2010. The median age of the patients was 72 (49–93) years at the time of surgery and 77 (51–97) years at the time of evaluation. The median follow‐up time was 34 (9–69) months. All patients had large malignant or semi‐malignant lid tumours. Data for subjective symptoms (OSDI questionnaire), lid margin morphology, tear break‐up time (BUT), vital staining, Schirmer test, impression cytology, tear film osmolarity, lipid layer interference patterns, meibography and the size of the tumour and flap were recorded and compared with the contralateral side. Results: Statistical analysis of the data revealed a significant difference between the surgically treated lid and the untreated side in meibomian gland loss, more lid margin abnormalities in the upper and lower eyelid (p < 0.001) and increased fluorescein staining of the cornea (p = 0.031). For the operated side, the median OSDI score was higher (17.2 versus 14.7), and the median BUT value was shorter (4.2 versus 5.6 seconds) compared with the median values of the contralateral side. Conclusion: Despite the favourable cosmetic and functional results of the Hughes tarsoconjunctival flap, our results indicate that this procedure does affect the ocular surface health in the treated eyes.