Anomalous Cosmic Rays and Heliospheric Energetic Particles.

We present a review of Anomalous Cosmic Rays (ACRs), including the history of their discovery and recent insights into their acceleration and transport in the heliosphere. We focus on a few selected topics including a discussion of mechanisms of their acceleration, escape from the heliosphere, their effects on the dynamics of the heliosheath, transport in the inner heliosphere, and their solar cycle dependence. A discussion concerning their name is also presented towards the end of the review. We note that much is known about ACRs and perhaps the term Anomalous Cosmic Ray is not particularly descriptive to a non specialist. We suggest that the more-general term: "Heliospheric Energetic Particles", which is more descriptive, for which ACRs and other energetic particle species of heliospheric origin are subsets, might be more appropriate.

Comparison of Interstellar Boundary Explorer observations with 3D global heliospheric models.

Simulations of energetic neutral atom (ENA) maps predict flux magnitudes that are, in some cases, similar to those observed by the Interstellar Boundary Explorer (IBEX) spacecraft, but they miss the ribbon. Our model of the heliosphere indicates that the local interstellar medium (LISM) magnetic field (B(LISM)) is transverse to the line of sight (LOS) along the ribbon, suggesting that the ribbon may carry its imprint. The force-per-unit area on the heliopause from field line draping and the LISM ram pressure is comparable with the ribbon pressure if the LOS approximately 30 to 60 astronomical units and B(LISM) approximately 2.5 microgauss. Although various models have advantages in accounting for some of the observations, no model can explain all the dominant features, which probably requires a substantial change in our understanding of the processes that shape our heliosphere.

Global observations of the interstellar interaction from the Interstellar Boundary Explorer (IBEX).

The Sun moves through the local interstellar medium, continuously emitting ionized, supersonic solar wind plasma and carving out a cavity in interstellar space called the heliosphere. The recently launched Interstellar Boundary Explorer (IBEX) spacecraft has completed its first all-sky maps of the interstellar interaction at the edge of the heliosphere by imaging energetic neutral atoms (ENAs) emanating from this region. We found a bright ribbon of ENA emission, unpredicted by prior models or theories, that may be ordered by the local interstellar magnetic field interacting with the heliosphere. This ribbon is superposed on globally distributed flux variations ordered by both the solar wind structure and the direction of motion through the interstellar medium. Our results indicate that the external galactic environment strongly imprints the heliosphere.

Frontal lobe dysfunctions in Korsakoff's syndrome and chronic alcoholism: continuity or discontinuity?

The effect of long-term heavy alcohol consumption on brain functions is still under debate. The authors investigated a sample of 17 Korsakoff amnesics, 23 alcoholics without Korsakoff's syndrome, and 21 controls with peripheral nerve diseases, matched for intelligence and education. Executive functions were examined for word fluency, the modified Wisconsin Card Sorting Test, an alternate response task, and an "n-back" working memory task. Korsakoff amnesics, but not alcoholics, showed a marked memory impairment. They also scored lower in each of the executive tasks-the alcoholics only in the alternate response task. This task also correlated with the years of the alcohol dependency. First, the authors conclude that Korsakoff's syndrome is associated not only with a memory impairment but also with a global executive deficit. Second, the decline in the ability to alternate between different responses argues for a restricted neurotoxic effect of alcohol on some frontal lobe areas.

Internal craniofacial distraction with biodegradable devices: early stabilization and protected bone regeneration.

Internal craniofacial distraction has several advantages over distraction with external devices. The scars may be less conspicuous; the devices are buried and therefore easier for patients to tolerate; and the devices are more rigidly secured to bone, preventing uncontrolled rotation of the advancing segments. There are several types of internal devices. The Modular Internal Distraction System developed by one of the authors (S.R.C.) and Stryker-Leibinger, Inc. has had widespread use for midface distraction, but requires a substantial surgical procedure for device removal. This is justified in selected children with syndromic craniosynostosis, who frequently need secondary orbitocranial reconstruction at the conclusion of distraction with any type of device. It would be preferable to develop a device that would retain the positive characteristics of the Modular Internal Distraction system, while allowing easy removability. Moreover, the entire distraction procedure would benefit from a technique that would assist in bone regeneration within the distraction gap. Such a biodegradable, stabilizing device may enable early explanation, accelerating the recovery period, while providing fixation of the distraction gap and protected bone regeneration. Accordingly, we have developed a new, biodegradable distraction device with Macropore, Inc. that may be used with the Modular Internal Distraction system to permit easy removability of the device without the need for a large operation for exposure. Second, we have developed a biodegradable stabilizer that permits earlier removal of the distraction device while providing simultaneous fixation and protected bone regeneration. Last, we have demonstrated the feasibility of midcourse correction of the distraction procedure, should this be necessary for whatever reason.

Demand for psychosocial counselling of young wheelchair users.

Young persons tied to wheelchairs increasingly report fears and inhibitions in romantic attachments, irrespective of whether they are paraplegic or not. More frequently they complain about being gaped at and being pitied by healthy persons more than they would like. Being tied to the wheelchair had a significant relation to these results, but not gender, age and illness variables. A high demand for psychosocial counselling during rehabilitation is deduced from these results, in particular also for young people without paraplegia.

A pulsar, the heliosphere, and pioneer 10: probable mimicking of a planet of PSR B1257+12 by solar rotation

Doppler data generated with the Pioneer 10 spacecraft's radio carrier wave between 1987 and 1995 show a 25.3-day periodicity which is related to the solar rotation. The timing data of the pulsar PSR B1257+12 also show a periodicity of 25.34 days, which has been explained as a signature of the pulsar's barycentric motion in response to the existence of a small moon-like object. However, because PSR B1257+12 is located close to the ecliptic and because the timing variations are in the range of microseconds, it is likely that the pulsar signal is affected by the same mechanism acting on the Pioneer 10 Doppler data. Hence, the hypothesized inner planet around PSR B1257+12 is probably an artifact of the heliosphere.

[Empirical results of adjustment to disability by adolescents with spina bifida and traumatic paraplegia]. / Empirische Ergebnisse zur Verarbeitung von Behinderung bei Jugendlichen mit Spina bifida und traumatischer Querschnittlähmung.

Between June 1991 and June 1992, a total of 39 rehabilitees aged 16 to 25 years were examined, i.e., 21 patients suffering from spina bifida and 18 patients suffering from traumatic paraplegia. Diagnostic instruments used were the Freiburg questionnaire on coping with illness (FKV 102), Goldberg et al's questionnaire for the evaluation of subjective wellbeing regarding health, and a self-constructed questionnaire for evaluating satisfaction with rehabilitation. Medical interviews on the present state of health and the present situation were held with each patient. The level of paralysis was taken as an indicator of the motor handicap present. The patients examined showed distinctly less confidence in doctors than adults do. From a subjective point of view, however, the confidence in doctors was good: among the coping strategies chosen, the compliance strategies ranked first and second, respectively, in the two groups. The coping strategy of "cognitive avoidance and dissimilation" is distinctly less common among spina bifida patients than among patients with traumatic paraplegia. They are less inclined to hope for a miracle, and take their handicap much more seriously than adolescents suffering from traumatic paraplegia. The higher the level of paraplegia, the more use is made of the coping strategy of "emotional control and social withdrawal". Regressive tendencies and depressive modes of coping were equally present in both groups. When investigating satisfaction with rehabilitation and with the own person, both groups showed very high satisfaction with the physical independence achieved and the possibilities of acting independently.(ABSTRACT TRUNCATED AT 250 WORDS)

[Rehabilitation of handicapped children as the combined responsibility of medicine and pedagogics--approach and contradictions in the process of integrated education]. / Förderung behinderter Kinder als gemeinsame Aufgabe von Medizin und Pädagogik--Anspruch und Widerspruch im Prozess integrativer Erziehung.

The development of common education of handicapped and non-disabled children in kindergartens and schools has removed all doubt that disabled children are encouraged and helped to a considerable degree whereas non-disabled children acquire more social aptitude. In no case need one fear that their learning performance is negatively affected by integrated education. This is of course conditional on the availability of suitable conditions under which such integrated education takes place. The medical profession as a whole did not participate in the development and testing of integrative models and test projects. The main reasons for this are difficulties in communication between physicians and educationists, which require to be discussed. The article describes the need for cooperation by physicians in further development of integrative measures, their possibilities of influencing the development, and their special task in cooperating with educational experts, from a paedogical aspects; finally, the sociopolitical and medicopolitical tasks of the medical profession in Public Health services are pointed out.

Gating in iodate-modified single cardiac Na+ channels.

Elementary Na+ currents were recorded at 19 degrees C during 220-msec lasting step depolarizations in cell-attached and inside-out patches from cultured neonatal rat cardiocytes in order to study the modifying influence of iodate, bromate and glutaraldehyde on single cardiac Na+ channels. Iodate (10 mmol/liter) removed Na+ inactivation and caused repetitive, burst-like channel activity after treating the cytoplasmic channel surface. In contrast to normal Na+ channels under control conditions, iodate-modified Na+ channels attain two conducting states, a short-lasting one with a voltage-independent lifetime close to 1 msec and, likewise tested between -50 and +10 mV, a long-lasting one being apparently exponentially dependent on voltage. Channel modification by bromate (10 mmol/liter) and glutaraldehyde (0.5 mmol/liter) also included the occurrence of two open states. Also, burst duration depended apparently exponentially on voltage and increased when shifting the membrane in the positive direction, but there was no evidence for two bursting states. Chemically modified Na+ channels retain an apparently normal unitary conductance (12.8 +/- 0.5 pS). Of the two substates observed, one of them is remarkable in that it is mostly attained from full-state openings and is very short living in nature; the voltage-independent lifetime was close to 2 msec. Despite removal of inactivation, open probability progressively declined during membrane depolarization. The underlying deactivation process is strongly voltage sensitive but, in contrast to slow Na+ inactivation, responds to a voltage shift in the positive direction with a retardation in kinetics. Chemically modified Na+ channels exhibit a characteristic bursting state much shorter than in DPI-modified Na+ channels, a difference not consistent with the hypothesis of common kinetic properties in noninactivating Na+ channels.

The response of single cardiac sodium channels in neonatal rats to the dihydropyridines CGP 28392 and (-)-Bay K 8644.

Cell-attached patch clamp recording of elementary Na+ currents were performed at 19 degrees C in neonatal cultured rat heart cells to study Na+ channel properties in the presence of dihydropyridines. Bath application of racemic CGP 28392, at 5 mumol/l, activated Na+ channels. By increasing the open probability, P0, and/or the number of functioning Na+ channels, peak INa in reconstructed macroscopic Na+ currents rose without changes in the decay kinetics. This was accompanied by a prolongation of open time. (-)-Bay K 8644 (1-10 mumol/l) had the same effect. In the presence of either agonist, Na+ channels retained an uniform open state and, as estimated from the mean number of openings per sequence, their initial tendency to reopen. Rarely appearing ultralong opening sequences are unlikely to be drug-induced as Na+ channels can likewise switch into this particular activity mode under drug-free conditions. Racemic CGP 28392, at 50 mumol/l, blocked Na+ channels in an all-or-none fashion suggesting that one enantiomer acts as agonist and the other enantiomer as blocker. A quite different response consisting of the occurrence of a second open state with a several-fold increased life time and a significantly increased reopening was observed with (-)-Bay K 8644 in damaged cardiocytes with hyperpermeable membranes and after patch excision into drug-containing solution. Evidence was obtained from control inside-out patches that this increased reopening is most probably caused by the solvent, ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolites of the glycolytic pathway modulate the activity of single cardiac Na+ channels.

Elementary Na+ currents through single cardiac Na+ channels were recorded at 19 degrees C in patch clamp experiments with cultured neonatal rat cardiocytes. The metabolites of the glycolytic pathway, 2,3-diphosphoglycerate and glyceraldehyde phosphate, were identified as a novel class of modulators of Na+ channel activity. In micromolar concentrations (1-10 mumol/liter), their presence at the cytoplasmic membrane face increased the number of sequential openings during depolarization and prolonged the conductive channel state. As found after ensemble averaging, the decay kinetics of reconstructed macroscopic Na+ currents became retarded and slow Na+ inactivation may have been evoked. Both metabolites attenuated the rundown of channel activity that regularly develops after patch excision in the inside-out patch configuration. It is tempting to assume that interference with Na+ inactivation is the mode of action underlying the increase in single-channel activity.

On the mechanism of drug-induced blockade of Na+ currents: interaction of antiarrhythmic compounds with DPI-modified single cardiac Na+ channels.

In patch-clamped membranes from neonatal rat cardiocytes, elementary Na+ currents were recorded at 19 degrees C for study of the inhibitory influence of several antiarrhythmic drugs including lidocaine, diprafenone, propafenone, and prajmalium on DPI-modified cardiac Na+ channels. Diprafenone (20 mumol/l) and lidocaine (300 mumol/l) induced a voltage- and time-dependent block of reconstructed macroscopic sodium current (INa). The drugs depressed the sustained, noninactivating INa component (which reflects the number and open probability of DPI-modified Na+ channels) effectively, in a voltage- and time-dependent fashion. Once opened, DPI-modified Na+ channels are highly drug-sensitive. Antiarrhythmic drugs (propafenone, diprafenone, and, to a lesser extent, lidocaine) provoke a flicker block, that is, the long-lasting openings are chopped into a large number of short and grouped openings. This indicates rapid transitions between a drug-associated, blocked state and a drug-free, conducting state. The latter has a unitary conductance of 12 pS, very similar to the control value in the absence of antiarrhythmic drugs. The decrease in open time of drug-treated DPI-modified Na+ channels is concentration-dependent. Hill coefficients for propafenone of about 1.0 and for prajmalium of about 0.7 were calculated. A blocking rate constant of 6.1 x 10(7) mol-1sec-1 for propafenone, but of 1.5 x 10(7) mol-1sec-1 for prajmalium was obtained at -30 mV. The unblocking rate constant for propafenone was, also at -30 mV, about twice as large as the unblocking rate constant for prajmalium. The open channel block kinetics are essentially voltage-dependent. The affinity of the channel-associated drug receptor increases on membrane depolarization. The blocking rate constant was inversely related to the number of Na+ ions moving through the open channel. It is concluded that the manifestation of this voltage- and Na+-dependent flicker block is intimately related to removal of fast Na+ inactivation.

Hyperpolarization and increased free calcium in acetylcholine-stimulated endothelial cells.

In freshly harvested aortic endothelial cells from rabbits, some cellular events associated with stimulation by acetylcholine (ACh) were analyzed. ACh (3 microM) induced a transient hyperpolarization of 8.3 +/- 2.5 mV, which peaked within 3-5 s and subsequently declined with a similar time course. Hyperpolarization was caused by a transient Ca2+-dependent outward current (IoACh), which was mainly carried by K+. ACh (3 and 10 microM) also evoked transient dose-dependent increases in the intracellular free Ca2+ concentration (Ca2+i). Pretreatment with atropine (1 and 3 microM) abolished both responses to ACh, the increase in Ca2+i as well as the transient outward current. It is concluded that IoACh and the rise in Ca2+i are two manifestations of muscarinic receptor stimulation. The rise in Ca2+i might be the primary event, leading to secondary membrane hyperpolarization.

Inhibitory effects of diprafenone stereoenantiomers on cardiac Na+ channels.

The potency of (-)- and (+)-diprafenone to depress the Vmax of Na+-dependent action potentials and to block single cardiac Na+ channels was analyzed in microelectrode experiments with guinea pig papillary muscles and in patch clamp experiments with DPI-modified Na+ channels using neonatal cardiocytes. Within 20-30 min, both optical enantiomers caused a Vmax depression which occurred predominantly as a phasic blockade at a low dosage (10 mumol/l). (-)- and (+)-diprafenone were equally effective in evoking a tonic and phasic depression of Vmax. Exposing the cytoplasmic side of inside-out patches to 10 mumol/l of (-)- or (+)-diprafenone evoked a flicker block of DPI-modified Na+ channels within 1-2 s. Kinetic analysis of the latter revealed a KD value for the blocking action of 6.3 X 10(-5) mol for the (-) enantiomer and 7.1 X 10(-5) mol for the (+) enantiomer. Nevertheless, larger association and dissociation rate constants were obtained with (+)-diprafenone than with (-)-diprafenone. This indicates that there are stereoselective reaction kinetics in blocking open modified Na+ channels.

Predominance of poorly reopening single Na+ channels and lack of slow Na+ inactivation in neonatal cardiocytes.

Elementary Na+ currents through single cardiac Na+ channels were recorded at -50 mV in cell-attached patches from neonatal rat cardiocytes kept at holding potentials between -100 and -120 mV. Na+ channel activity may occur as burst-like, closely-timed repetitive openings with shut times close to 0.5-0.6 msec, indicating that an individual Na+ channel may reopen several times during step depolarization. A systematic quantitative analysis in 19 cell-attached patches showed that reopening may be quite differently pronounced. The majority, namely 16 patches, contained Na+ channels with a low tendency to reopen. This was evidenced from the average value for the mean number of openings per sequence, 2.5. Strikingly different results were obtained in a second group of three patches. Here, a mean number of openings per sequence of 3.42, 3.72, and 5.68 was found. Ensemble averages from the latter group of patches revealed macroscopic Na+ currents with a biexponential decay phase. Reconstructed Na+ currents from patches with poorly reopening Na+ channels were devoid of a slow decay component. This strongly suggests that reopening may be causally related to slow Na+ inactivation. Poorly pronounced reopening and, consequently, the lack of slow Na+ inactivation could be characteristic features of neonatal cardiac Na+ channels.

[Extraosseous calcification in juvenile dermatomyositis. The ineffectiveness of EHDP]. / Extraossäre Calcifikationen bei juveniler Dermatomyositis. Unwirksamkeit von EHDP.

A now 20-year-old man was first diagnosed as having dermatomyositis when aged 12 years. At that time he had muscular weakness and heart failure followed a year later by heterotopic calcifications. For over seven years he was treated with corticoids, at times also with azathioprine or methotrexate. Nonetheless the calcifications progressed. Because of the extensive calcifications, predominantly of the extremities, he is severely disabled and has been confined to a wheel-chair. For one year he was treated with EHDP (1-hydroxyethylidenediphosphonate), up to 16 mg/dl per day. In addition he received prednisolone (10 mg/d) and azathioprine (100 mg/d). But radiologically there has been further slight progression of the calcifications, indicating that EHDP has been ineffective in this patient.

Block of single cardiac Na+ channels by antiarrhythmic drugs: the effect of amiodarone, propafenone and diprafenone.

Cell-attached patch-clamp experiments were performed in cultured cardiocytes of neonatal rats at 19 degrees C to analyze elementary currents through single Na+ channels under control conditions and in the presence of the class 1 antiarrhythmic drugs amiodarone, propafenone, and diprafenone. As observed in a cell-attached patch with only one functioning Na+ channel, repetitive stepping of the membrane at 0.4 Hz triggered periodically channel openings except during a silent period of about 1.5 min. The latter began and ceased abruptly and did not fit the monoexponential distribution of the run length of sweeps without activity (blank sweeps). Treating the cardiocytes with amiodarone, propafenone or diprafenone (10 to 20 mumol/liter) led rapidly to a blockage and reduced the likelihood that membrane depolarization triggers the opening of Na+ channels. The number of blank sweeps increased at the expense of the number of sweeps with activity. The fraction of activity sweeps with superpositions, indicating the simultaneous activation of two or more Na+ channels, also declined. As tested with amiodarone, the run length of blank sweeps is voltage- and time-dependent, analogous to the intensity of the block of macroscopic Na+ currents. Open time, open-time distribution, unitary current size and the tendency to reopen did not differ in unblocked cardiac Na+ channels (i.e. that channel fraction capable of opening in the presence of amiodarone or propafenone) from the respective control values obtained before superfusing the cardiocytes with these drugs. Apart from its blocking action, the propafenone derivative diprafenone exerted additionally a modifying effect and reduced mean open time by up to 45%. In contrast to the block, this reduction in conducting state proved insensitive to changes in holding potential, at least between -130 and -150 mV, the range tested. This means that block was attenuated on hyperpolarization whereas the reduction in open time persisted. It is concluded that, in the presence of these drugs, unblocked cardiac Na+ channels share a number of properties with normal Na+ channels in the absence of these drugs. Shortening of channel lifetime by diprafenone may be indicative of a channel modification brought about possibly by a receptor-mediated facilitation of the transition from the open to the inactivated state.

Differences in open state of NBA-modified cardiac Na+ channels.

Patch clamp recordings from neonatal cardiac Na+ channels treated with N-bromoacetamide (NBA, 5-50 X 10- mol/l) showed modified Na+ channel activity. By chemical removal of inactivation, repetitive openings with an increased life time and burst-like activity occurred. NBA-modified Na+ channels differ in life time and may attain either a slightly (mean open time 3.1 +/- 0.2 ms) or a strongly (mean open time 15.2 +/- 1.4 ms) prolonged open state. This strongly suggests a heterogeneous population of NBA-modified Na+ channels in newborn rat cardiocytes.