Effects of preference and sensory modality on behavioural reaction in patients with disorders of consciousness.

BACKGROUND: Reliable evaluation of patients with unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS) remains a major challenge. It has been suggested that the expression of residual cerebral function could be improved by allowing patients to listen to their favourite music. However, the potential effect of music on behavioural responsiveness, as well as the effect of preferred stimuli in other sensory modalities (e.g. olfaction), remain poorly understood. OBJECTIVE: The aim of our study was to investigate the effect of sensory modality (auditory versus olfactory) and preference (preferred versus neutral) of the test stimuli on patients' subsequent performance on the Coma Recovery Scale-Revised (CRS-R). RESEARCH DESIGN: Within-subject design because of inter-individual differences between patients. METHODS AND PROCEDURES: We studied four items from the CRS-R (visual pursuit using a mirror, auditory localization of the own name and two movements to command) in 13 patients (7 MCS; 6 UWS). MAIN OUTCOMES AND RESULTS: Auditory stimuli triggered higher responsiveness compared to olfactory stimuli, and preferred stimuli were followed by higher scores than did neutral stimuli. CONCLUSIONS: Findings suggest that preferred auditory stimuli at the bedside contribute to the expression of residual function and could improve the diagnostic assessment.

Function-structure connectivity in patients with severe brain injury as measured by MRI-DWI and FDG-PET.

A vast body of literature exists showing functional and structural dysfunction within the brains of patients with disorders of consciousness. However, the function (fluorodeoxyglucose FDG-PET metabolism)-structure (MRI-diffusion-weighted images; DWI) relationship and how it is affected in severely brain injured patients remains ill-defined. FDG-PET and MRI-DWI in 25 severely brain injured patients (19 Disorders of Consciousness of which 7 unresponsive wakefulness syndrome, 12 minimally conscious; 6 emergence from minimally conscious state) and 25 healthy control subjects were acquired here. Default mode network (DMN) function-structure connectivity was assessed by fractional anisotropy (FA) and metabolic standardized uptake value (SUV). As expected, a profound decline in regional metabolism and white matter integrity was found in patients as compared with healthy subjects. Furthermore, a function-structure relationship was present in brain-damaged patients between functional metabolism of inferior-parietal, precuneus, and frontal regions and structural integrity of the frontal-inferiorparietal, precuneus-inferiorparietal, thalamo-inferioparietal, and thalamofrontal tracts. When focusing on patients, a stronger relationship between structural integrity of thalamo-inferiorparietal tracts and thalamic metabolism in patients who have emerged from the minimally conscious state as compared with patients with disorders of consciousness was found. The latter finding was in line with the mesocircuit hypothesis for the emergence of consciousness. The findings showed a positive function-structure relationship within most regions of the DMN. Hum Brain Mapp 37:3707-3720, 2016. © 2016 Wiley Periodicals, Inc.

Mindsight: diagnostics in disorders of consciousness.

Diagnosis of patients with disorders of consciousness (comprising coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state) has long been dependent on unstandardized behavioral tests. The arrival of standardized behavioral tools, and especially the Coma Recovery Scale revised, uncovered a high rate of misdiagnosis. Ancillary techniques, such as brain imaging and electrophysiological examinations, are ever more often being deployed to aid in the search for remaining consciousness. They are used to look for brain activity patterns similar to those found in healthy controls. The development of portable and cheaper devices will make these techniques more widely available.

Incidence of abnormal cerebral findings in the MRI of clinically healthy divers: role of a patent foramen ovale.

BACKGROUND: To investigate incidence and number of abnormal cerebral hyperintensities (ACFs) in Magnet Resonance Imaging (MRI) and its relation to a patent foramen ovale (PFO) in divers with no history of decompression illness. METHODS: Cohort study on 50 divers (21-5500 dives). MAIN OUTCOME MEASURES: Incidence and number of ACFs visualized by cranial MRI and presence and size of a PFO as documented by echocardiography and transcranial Doppler ultrasound (TCD) with echocontrast. RESULTS: A total of 137 ACFs was found in the 50 subjects, with a significant correlation between the number of dives and number of ACFs (r = 0.28; p < 0.05); but after correction for age, the remaining correlation (r = 0.15) did not reach significance. In 18 divers, a PFO was present by either the application of echocardiography or TCD; in 12 divers, the PFO was of high hemodynamic relevance. Ten of 18 divers with a PFO had at least one ACF, while in the remaining 32 divers, only 14 had at least one ACF (56% versus 44%, p = NS). Seven of 14 divers (50%) with 4 ACFs had a PFO, compared to 11 of 36 (31%) with less than 4 ACFs (p = NS). CONCLUSION: In this cohort of healthy divers, in contrast to an earlier report, no significant association was found between PFO presence and incidence or number of ACFs.

Effects of ambient cold and depth on lung function in humans after a single scuba dive.

This study evaluated the subacute respiratory effects of diving, to try to separate the effects of ambient temperature from those of depth. In the first experiment 10 healthy men made a compressed-air dive to 50 m that exposed them to cold. They were compared with 10 matched control subjects who underwent the same dive profile but were exposed to a comfortable temperature. In the second experiment 16 healthy subjects made randomized cold dives to both 50 m and 10 m. Pulmonary function tests were made before, after 1 h, and 24 h after the dives. In the first experiment there was an increase in residual volume (P < 0.05) and a decrease in forced expiratory volume at 1 s (FEV1), in forced vital capacity (FVC) and in mid-expiratory flow at 75% of FVC (MEF75) 1 h after the cold dives (P < 0.05). In the second experiment significant increases in specific airways resistance (sR(AW)) (P < 0.05) and decreases in FEV1 (P<0.01), in MEF75 (P<0.05), and in mid-expiratory flow at 25% of FVC (P<0.05), were obtained after the 50 m-dives, whereas SR(AW) increased after the 10 m-dives (P<0.05). The respiratory pattern observed 1 h after cold dives to 50 m indicated airway narrowing. The changes after cold dives to 10 m, however, were of minor magnitude. Both cold and depth seemed to contribute to the adverse effects of a single compressed-air dive on pulmonary function.

[Simultaneous transthoracic echocardiography and transcranial doppler ultrasonography with ultrasound contrast agents for the detection of a patent foramen ovale in diving medicine]. / Simultane transthorakale Echokardiographie und transkranielle Dopplersonographie mit Ultraschallkontrastmittel zum Nachweis eines persistenten Foramen ovale in der Tauchmedizin.

OBJECTIVE: Presentation of a non-invasive method for the identification of a patent foramen ovale (PFO) in screening of diving-candidates or for the investigation of diving accidents. METHOD: Simultaneous transthoracic echocardiography and transcranial Doppler sonography of the middle cerebral artery using ultrasound contrast media. RESULTS: In an unselected collective of amateur and professional divers a PFO was identified according to statistical prediction. CONCLUSION: This method can be used in diving medicine for PFO detection as an alternative procedure to transesophageal echocardiography.

Physical activity and stages of change in fifth and sixth graders.

The Stage of Change (SC) paradigm was adapted to assess readiness to be or stay physically active among fifth and sixth graders. Students completed a four-item SC survey, the Past Year Leisure Time Physical Activity Questionnaire, and the Modifiable Physical Activity Questionnaire for Adolescents. Precontemplation, contemplation, and preparation stages were grouped as "pre-action" (PRE), and action and maintenance as "post-action" (AX) stages. Nearly 40% of all students were in PRE, compared to 60% of students in AX stages. Twenty-two percent of all students were in the sedentary precontemplation or contemplation stages. Significantly more boys were in maintenance than girls, and more girls than boys were in contemplation. Students averaged 14-21 hours/week of television, video, or computer work, and 1.6 hours/week of physical activity outside of school. Interventions may be targeted at a specific SC to enable a child to move forward along the SC continuum toward an active lifestyle.

Respiratory pattern after wet and dry chamber dives to 0.6 MPa ambient pressure in healthy males.

The purpose of this study was to evaluate respiratory effects of wet and dry hyperbaric chamber dives to 0.6 MPa ambient pressure in healthy males. There were 19 and 22 subjects who participated in two series of dives with a bottom time of 15 min and decompression times of 28 and 17 min, respectively. Airways conductance, residual volume, forced vital capacity, forced expiratory volume in 1 sec, mid expiratory flow at 25, 50 and 75% of FVC, and diffusion capacity for CO were measured before the dives, after 3 h, and after 24 h. Multivariate analysis of covariance revealed no statistically significant effects of time or the interaction between time and dry or wet environment on the measured lung function parameters. These findings suggest first that even deep air dives may not necessarily affect pulmonary function, and second, that factors related to the particular wet environment do not seem to contribute to lung function changes after dives.

Long-term transcutaneous electrical nerve stimulation (TENS) use: impact on medication utilization and physical therapy costs.

OBJECTIVE: A study was conducted to assess a variety of treatment outcomes in long-term users of transcutaneous electrical nerve stimulation (TENS) who suffer from chronic pain. Key components of the study examined the effects of long-term TENS therapy on pain-related medications and physical/occupational therapy (PT/OT) use. DESIGN: From a population of 2,(X)3 chronic pain patients (CPPs) who acquired a TENS device (Epix XL, Empi, Inc., St. Paul, MN, U.S.A.) for pain management, a randomly selected sample of 376 patients who used TENS were interviewed by telephone by an independent research firm. The survey assessed a variety of outcome variables including changes in medication use, number of pain-related medications, and use of PT/OT prior to TENS and after a minimum 6 months of TENS treatment. The data were subjected to a paired t test analysis. A cost simulation model was then applied to the medication and PT/OT data. RESULTS: The mean duration of pain, for which TENS was prescribed, was 40 +/- 60 months. As compared with the period prior to TENS use, this long-term TENS user group reported a statistically significant reduction in the following types of pain medications: opiate analgesics, tranquilizers, muscle relaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids. PT/OT use was also significantly reduced. Cost simulations of pain medications and PT/OT are presented. CONCLUSIONS: Long-term use of TENS is associated with a significant reduction in the utilization of pain medication and PT/OT. In this study population, cost simulations of medication and PT/OT indicate that with long-term TENS use, costs can be reduced up to 55% for medications and up to 69% for PT/OT. The potential for TENS associated improvement, combined with reduced medication-related complications and costs, are important points that clinicians should consider when constructing a treatment plan for chronic pain patients. Finally, cost simulation techniques provide a useful tool for assessing outcomes in pain treatment and research.

Acceleration of hepatocellular energy by idebenone during early reperfusion after cold preservation ameliorates heat shock protein 70 gene expression in a pig liver model.

BACKGROUND: Heat shock proteins (HSPs) are induced in the liver after warm ischemia/reperfusion and are thought to be markers of hepatocellular injury and oxidative stress. METHODS: The influence of variable periods of cold storage followed by reperfusion on the expression of HSP70 was studied in the isolated perfused pig liver. Organs were harvested and stored in histidine-tryptophan-ketoglutarate solution at 4 degrees C and then perfused (210 min) in a closed water bath (38 degrees C), which subjects the liver to fluctuating outer pressure. The role of energy depletion, reactive oxygen intermediates, Kupffer cells, and circulating leukocytes in HSP70 expression was determined. RESULTS: HSP70 expression was not detectable in liver tissue before explantation or before reperfusion by Northern blot analysis using a pig HSP70 gene probe. HSP70 expression was observed after reperfusion depending on cold storage time. Kinetics of HSP70 expression monitored by reverse transcriptase polymerase chain reaction showed a rapid increase of mRNA within 1 hr, which was closely associated with delayed recovery of hepatocellular energy charge, as assessed by the ketone body ratio. The inactivation of Kupffer cells, the presence or absence of leukocytes, and the suppression of oxidative stress with the antioxidant idebenone, given during reperfusion, had no influence. However, feeding the animals with idebenone over 7 days before explantation led to a faster recovery of ketone body ratio, paralleled by a substantial suppression of HSP70 expression. CONCLUSIONS: Our data show that HSP70 expression during reperfusion is mainly dependent on the preceding cold storage time and the consecutive delayed recovery of the hepatocellular energy charge.

Optimization of transfection of human endothelial cells.

Recently developed transfection methods for mammalian cells provide a powerful means for the study of gene function. Unfortunately, human endothelial cells were relative refractory to the classic transfection techniques. In this study we compared the usability of calcium phosphate, DEAE-dextran transfection, transferrinfection, lipofection, and electroporation for the transfection of early passage HUVECs and for the human endothelial cell lines ECV 304 and EA.hy 926. The classic transfection methods resulted in no or only marginal expression of the reporter gene E. coli beta-galactosidase. For lipofection experiments we compared the commercially available liposome formulations DOTAP and Transfectam with liposomes prepared of dimethyldioctadecylammoniumbromide (DDAB) or 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide (DMRIE) as the cationic lipid compound and dioleylphosphatidylethanolamine (DOPE) or Azolectin (a crude fraction of soybean lipids, commercially available as phosphatidylcholine II) as neutral co-lipid. Because the protocol for the chemical synthesis of DMRIE has not been published yet, we developed a protocol for the chemical synthesis of this cationic lipid. With transfection protocols optimized for each cell line, we could achieve transfection efficiencies up to 2%. Compared to the other methods used, the lipofection proved to be a reliable technique for the efficient transfection of the human endothelial cell lines ECV 304 and EA.hy 926. Although we achieved a maximum transfection efficiency of 0.45% for the lipofection of HUVEC, the electroporation seemed to be the better choice for these cells.

Transcutaneous electrical nerve stimulation (TENS) treatment outcome in long-term users.

OBJECTIVE: Previous reviewers of the literature on transcutaneous electrical nerve stimulation (TENS) outcome have concluded the following: (a) there are few long-term TENS follow-up studies, and (b) fewer studies have addressed the effect of long-term TENS use on outcome variables other than pain (e.g., function). DESIGN/SETTING/PARTICIPANTS/OUTCOME MEASURES: From a population of 2,003 chronic pain patients (CPPs) who bought a TENS device for pain management, 506 patients were randomly selected and interviewed by telephone long enough after purchase to allow at least 6 months of TENS use. The interview process used a structured "skip" questionnaire designed to assess the CPPs' perceptions regarding the effectiveness of TENS for a variety of outcome variables. Of the 506 CPPs interviewed, 376 (74.3%) had used their TENS device for 6 months or longer and were defined as long-term users. The responses of this group of CPPs to the telephone questionnaire were then subjected to statistical analysis. RESULTS: Paired t-tests, correlated z-tests, SS Wilks, and chi-square tests demonstrated statistically significant change or improvement (p < 0.05) that paralleled the introduction of TENS use in the following outcome variables: less pain interference with work, home, and social activities; increased activity level and pain management; decreased use of other therapies (e.g., physical therapy, occupational therapy, chiropractic); decreased use of narcotics, tranquilizers, muscle relaxants, nonsteroidal anti-inflammatory drugs and steroids. CONCLUSIONS: The results suggest that TENS is associated with improvement on multiple outcome variables in addition to pain relief for CPPs who are long-term users. Also, for some CPPs, long-term TENS use continues to be effective.

Induction of heat shock protein 70 genes in human lymphocytes during fever therapy.

The induction of heat shock protein 70 (HSP70) genes has been studied in peripheral blood mononuclear cells of individuals undergoing fever therapy because of metastatic malignant melanoma. Induction of HSP70 was assessed at the protein level by metabolic labelling or, for the HLA-linked HSP70-1 and HSP70-2 genes, at the RNA level by in situ hybridization. However, de novo expression of HSP70 could be observed during fever (usually above 39 degrees C) in only about half of the cases. No simple threshold model for inducibility of HSP70 in vivo could be applied. The HSP70-1 gene was induced more easily than HSP70-2. Thus, heat-inducible HSP70 genes, including HLA-linked HSP70 genes, become expressed in human lymphocytes during fever, but not regularly.

Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells.

Mice deficient for the major lysosomal aspartic proteinase cathepsin D, generated by gene targeting, develop normally during the first 2 weeks, stop thriving in the third week and die in a state of anorexia at day 26 +/- 1. An atrophy of the ileal mucosa first observed in the third week progresses towards widespread intestinal necroses accompanied by thromboemboli. Thymus and spleen undergo massive destruction with fulminant loss of T and B cells. Lysosomal bulk proteolysis is maintained. These results suggest, that vital functions of cathepsin D are exerted by limited proteolysis of proteins regulating cell growth and/or tissue homeostasis, while its contribution to bulk proteolysis in lysosomes appears to be non-critical.

Effect of heat shock on susceptibility of normal lymphoblasts and of a heat shock protein 70-defective tumour cell line to cytotoxic T lymphocytes in vitro.

The effect of heat shock pretreatment of target cells on their lysability by cytotoxic T lymphocytes was analysed. Killing of Concanavalin A-stimulated normal lymphocytes by minor or major histocompatibility antigen-specific cytotoxic T lymphocytes is unchanged or even slightly enhanced after heat shock, whereas cells of the myeloma line Y3, which is derived from one of the lymphocyte donor strains, become nearly resistant to killing after the same pretreatment. Cold target inhibition experiments show that heat-shocked cells are recognized specifically and that untreated and heat-shocked target cells possess similar inhibitory potential. Y3 cells are unable to express the strongly heat-inducible heat shock protein of 70 kDa (hsp70) after heat shock; the acquired resistance is thus independent of hsp70 induction. Possible mechanisms of the different lysability seen in lymphoblasts and tumour cells after heat shock are discussed.