First case report of pre-mortem biopsy-proven kidney involvement by necrobiotic xanthogranuloma with monoclonal gammopathy.

Necrobiotic xanthogranuloma (NXG) is a rare non-Langerhans cell histiocytosis with characteristic cutaneous features and rare visceral involvement. More than 80% of individuals with this disease have a detectable paraprotein but the precise pathogenesis remains obscure. A 68-year-old man with known cutaneous necrobiotic xanthogranuloma presented with acute kidney injury and imaging suggestive of bilateral perinephric infiltration. Renal biopsy showed a prominent histiocytic infiltration of renal capsule and cortex with necrobiosis and characteristic 'Touton-type' giant cells suggestive of necrobiotic xanthogranuloma involvement. Kidney function returned to normal and cutaneous lesions improved with a combination of corticosteroid, chlorambucil and rituximab. This case represents only the second reported incidence of kidney involvement by necrobiotic xanthogranuloma and the first with acute kidney injury and pre-mortem histopathology. This report adds to a small body of literature on the diagnosis and management of visceral involvement by this rare disease.

Psychogenic seizures and psychogenic movement disorders: are they the same patients?

Psychogenic nonepileptic seizures (PNES) and psychogenic movement disorders (PMD) are common and disabling problems with abnormal psychological profiles, and they may have common features that could aid in better understanding and management. Since PNES and PMD are investigated and reported separately, comparisons are lacking. Psychogenic nonepileptic seizure and psychogenic movement disorder patients completed demographic, clinical, and psychological inventories including the Short Form (SF)-12 Health Status Survey (Physical and Mental Health Summary Scores), the Brief Symptom Inventory (BSI)-18 (somatization, depression, and anxiety subscales), and the Lorig Self-Efficacy Scale. Psychogenic nonepileptic seizure and psychogenic movement disorder patients had similar psychological profiles with reduced SF-12 Physical Health and Mental Health Summary Scores and increased BSI somatization, depression, and anxiety ratings. They varied slightly in age and gender, but their main distinguishing features were the presenting signs. These similar profiles suggest that PNES and PMD may not be distinct or separate entities and that collaborative investigative efforts and management are warranted.

Evaluation of neutron sources for ISAGE-in-situ-NAA for a future lunar mission.

For a future Moon landing, a concept for an in-situ NAA involving age determination using the (40)Ar-(39)Ar method is developed. A neutron source (252)Cf is chosen for sample irradiation on the Moon. A special sample-in-source irradiation geometry is designed to provide a homogeneous distribution of neutron flux at the irradiation position. Using reflector, the neutron flux is likely to increase by almost 200%. Sample age of 1Ga could be determined. Elemental analysis using INAA is discussed.

Acute effect of a single bout of aerobic exercise on vascular and baroreflex function of young males with a family history of hypertension.

The effect of one single bout of aerobic exercise on the vascular and baroreceptor function of individuals with a family history of hypertension was investigated. Forty young males, mean age 21 years, comprising offspring with (FH(+); n=20) and without (FH(-); n=20) a family history of hypertension participated in this study. Acute exercise was performed on a stationary bike for 20 min at 60% of maximal oxygen uptake. Peak forearm blood flow (FBF) was assessed using plethysmography and was determined as the highest blood flow after 5 min of reactive hyperaemia. Cardiopulmonary baroreceptor (CPBR) sensitivity was measured using lower-body negative pressure (LBNP) for 5 min at -20 mm Hg. CPBR was determined by calculating change of stroke volume and forearm vascular resistance (FVR) at baseline and during LBNP. Carotid baroreceptor (CBR) sensitivity was assessed using neck suction at -20, -40, -60 and -80 mm Hg pressures and was determined from RR interval divided by systolic blood pressure. Augmentation index (AIx), a measure of wave reflection, was assessed using applanation tonometry, and was calculated as the ratio of augmented pressure and pulse pressure. The peak FBF at pre-exercise was lower in FH(+) than in FH(-) subjects. Twenty minutes of acute cycle exercise resulted in significantly increased peak FBF by 22% in FH(+) and by 11% in FH(-) subjects, whereas peak FVR of both groups decreased by 17% and 11%, respectively. No change occurred in CPBR, CBR or AIx. It is concluded that 20 min of acute cycle exercise normalised baseline FBF and forearm vasodilation during hyperaemia in FH(+) subjects.

Identifying sites of saccade amplitude plasticity in humans: transfer of adaptation between different types of saccade.

To view different objects of interest, primates use fast, accurate eye movements called saccades. If saccades become inaccurate, the brain adjusts their amplitudes so they again land on target, a process known as saccade adaptation. The different types of saccades elicited in different behavioral circumstances appear to utilize different parts of the oculomotor circuitry. To gain insight into where adaptation occurs in different saccade pathways, we adapted saccades of one type and examined how that adaptation affected or transferred to saccades of a different type. If adaptation of one type of saccade causes a substantial change in the amplitude of another, that adaptation may occur at a site used in the generation of both types of saccade. Alternatively, if adaptation of one type of saccade transfers only partially, or not at all, to another, adaptation occurs at least in part at a location that is not common to the generation of both types of saccade. We produced significant amplitude reductions in memory-guided, delayed, targeting and express saccades by moving the target backward during the saccade. After memory-guided saccades were adapted, the amplitude of express, targeting and delayed saccades exhibited only a partial reduction. In contrast, when express, targeting, or delayed saccades were adapted, amplitude transfer to memory-guided saccades was more substantial. These results, combined with previously published data, suggest that there are at least two sites of adaptation within the saccadic system. One is used communally in the generation of express, targeting, delayed and memory-guided saccades, whereas the other is specific for the generation of memory-guided saccades.

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. METHODS: A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007. RESULTS: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. RECOMMENDATIONS: Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations.

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. METHODS: A 20-member committee including general neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and February 2008. RESULTS: For WWE taking antiepileptic drugs, there is probably no substantially increased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84%-92%) of remaining seizure-free during pregnancy. RECOMMENDATIONS: Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%-92%) of remaining seizure-free during pregnancy (Level B). However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy (Level C).

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. METHODS: Systematic review of relevant articles published between January 1985 and June 2007. RESULTS: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. RECOMMENDATIONS: If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of <7 (Level C).

Practice Parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology develops practice parameters as strategies for patient care based on analysis of evidence. For this practice parameter the authors reviewed available evidence relevant to evaluating adults presenting with an apparent unprovoked first seizure. METHODS: Relevant questions were defined and addressed by multiple searches of medical literature. Each article was then reviewed, abstracted, and classified using an established evidence scoring system. Conclusions and recommendations were based on a standard three-tiered scheme of evidence classification. RESULTS: For adults presenting with a first seizure, a routine EEG revealed epileptiform abnormalities in approximately 23% of patients, and these were predictive of seizure recurrence. A brain imaging study (CT or MRI) was significantly abnormal in 10% of patients, indicating a possible seizure etiology. Laboratory tests such as blood counts, blood glucose, and electrolyte panels were abnormal in up to 15% of individuals, but abnormalities were minor and did not cause the seizure. Overt clinical signs of infection such as fever typically predicted significant CSF abnormalities on lumbar puncture. Toxicology screening studies were limited, but report some positive tests. RECOMMENDATIONS: EEG should be considered as part of the routine neurodiagnostic evaluation of adults presenting with an apparent unprovoked first seizure (Level B). Brain imaging with CT or MRI should be considered as part of the routine neurodiagnostic evaluation of adults presenting with an apparent unprovoked first seizure (Level B). Laboratory tests, such as blood counts, blood glucose, and electrolyte panels (particularly sodium), lumbar puncture, and toxicology screening may be helpful as determined by the specific clinical circumstances based on the history, physical, and neurologic examination, but there are insufficient data to support or refute recommending any of these tests for the routine evaluation of adults presenting with an apparent first unprovoked seizure (Level U).

Amplitude adaptation occurs where a saccade is represented as a vector and not as its components.

When saccades become inaccurate, their amplitude is adapted. We examined, in humans, whether this adaptation occurs where the saccade is represented as a vector or as its horizontal and vertical components. In one experiment, we behaviorally reduced the amplitude of clockwise oblique saccades and examined the transfer to saccades made to other target amplitudes and directions. In a second, we adapted rightward saccades of the same size as the rightward component of the clockwise oblique saccades and examined the effect on oblique saccades. The results of both experiments imply that adaptation occurs where the saccade command is represented as a vector.

The characteristics and neuronal substrate of saccadic eye movement plasticity.

Saccadic eye movements are shifts in the direction of gaze that rapidly and accurately aim the fovea at targets of interest. Saccades are so brief that visual feedback cannot guide them to their targets. Therefore, the saccadic motor command must be accurately specified in advance of the movement and continually modified to compensate for growth, injury, and aging, which otherwise would produce dysmetric saccades. When a persistent dysmetria occurs in subjects with muscle weakness or neural damage or is induced in normal primates by the surreptitious jumping of a target forward or backward as a saccade is made to acquire the target, saccadic amplitude changes to reduce the dysmetria. Adaptation of saccadic amplitude or direction occurs gradually and is retained in the dark, thus representing true motor plasticity. Saccadic adaptation is more rapid in humans than in monkeys, usually is incomplete in both species, and is slower and less robust for amplitude increases than decreases. Adaptation appears to be motor rather than sensory. In humans, adaptation of saccades that would seem to require more sensory-motor processing does not transfer to saccades that seem to require less, suggesting the existence of distributed adaptation loci. In monkeys, however, transfer from more simple to more complex saccades is robust, suggesting a common adaptation site. Neurophysiological data from both species indicate that the oculomotor cerebellum is crucial for saccadic adaptation. This review shows that the precise, voluntary behaviors known as saccadic eye movements provide an alternative to simple reflexes for the study of the neuronal basis of motor learning.

Investigating the site of human saccadic adaptation with express and targeting saccades.

To focus on various objects of interest within the visual environment, primates employ rapid eye movements called saccades. When the accuracy of these movements becomes impaired, the brain can adjust their amplitude by a process known as saccadic adaptation. To investigate the locus of this plasticity in the human brain, we behaviorally adapted two types of saccade thought to be generated through different neuronal pathways. Targeting saccades, which are made to sequentially illuminated targets and have long latencies, are thought to involve higher cortical processing whereas express saccades, which have very short latencies, apparently do not. If adaptation transfers between these two types of saccade, one may conclude that the plasticity must exist at a locus common to the two pathways generating these saccades. We directly reduced the gain of either targeting or express saccades by intrasaccadically moving the target one-third of its amplitude back toward the initial fixation location and then examined whether the gain was also reduced in the other type of saccade. When targeting saccades were adapted directly, all subjects showed significant reductions in the gain of these saccades. In 75% of the 32 experimental target conditions across all subjects, there were also significant reductions in the gain of express saccades, thus providing evidence of adaptation transfer. In 71% of these conditions (i.e., 53% of all target conditions) there was no significant difference between the reductions in gain of the two types of saccade, suggesting that adaptation transfer was complete (100%). Similar results were obtained when express saccades were adapted directly: significant reductions in gain occurred in 91% of express saccades and in 100% of targeting saccades. In 86% of the target conditions, across subjects, in which both express and targeting saccades showed significant reductions in gain, the two types of saccade did not differ significantly in the amount of gain reduction. This suggests that adaptation transfer was complete for 78% of all target conditions. Therefore, we conclude that saccadic adaptation transfers robustly between targeting and express saccades. These results suggest that adaptation in humans occurs after the pathways generating these two types of saccade converge, probably at or downstream from the superior colliculus.

Mechanical trade-offs explain how performance increases without increasing cost in rattlesnake tailshaker muscle.

Rattling by rattlesnakes is one of the fastest vertebrate movements and involves some of the highest contraction frequencies sustained by vertebrate muscle. Rattling requires higher accelerations at higher twitch frequencies, yet a previous study showed that the cost per twitch of rattling is independent of twitch frequency. We used force and video recordings over a range of temperatures to examine how western diamondback rattlesnakes (Crotalus atrox) achieve faster movements without increases in metabolic cost. The key findings are (i) that increasing muscle twitch tension trades off with decreasing twitch duration to keep the tension-time integral per twitch nearly constant over a wide range of temperatures and twitch frequencies and (ii) that decreasing lateral displacement of the rattle joint moderates the mechanical work and power required to shake the rattle at higher frequencies. These mechanical trade-offs between twitch tension and duration and between joint force and displacement explain how force, work and power increase without an increase in metabolic cost.

RGS9-G beta 5 substrate selectivity in photoreceptors. Opposing effects of constituent domains yield high affinity of RGS interaction with the G protein-effector complex.

RGS proteins regulate the duration of G protein signaling by increasing the rate of GTP hydrolysis on G protein alpha subunits. The complex of RGS9 with type 5 G protein beta subunit (G beta 5) is abundant in photoreceptors, where it stimulates the GTPase activity of transducin. An important functional feature of RGS9-G beta 5 is its ability to activate transducin GTPase much more efficiently after transducin binds to its effector, cGMP phosphodiesterase. Here we show that different domains of RGS9-G beta 5 make opposite contributions toward this selectivity. G beta 5 bound to the G protein gamma subunit-like domain of RGS9 acts to reduce RGS9 affinity for transducin, whereas other structures restore this affinity specifically for the transducin-phosphodiesterase complex. We suggest that this mechanism may serve as a general principle conferring specificity of RGS protein action.

The effector enzyme regulates the duration of G protein signaling in vertebrate photoreceptors by increasing the affinity between transducin and RGS protein.

The photoreceptor-specific G protein transducin acts as a molecular switch, stimulating the activity of its downstream effector in its GTP-bound form and inactivating the effector upon GTP hydrolysis. This activity makes the rate of transducin GTPase an essential factor in determining the duration of photoresponse in vertebrate rods and cones. In photoreceptors, the slow intrinsic rate of transducin GTPase is accelerated by the complex of the ninth member of the regulators of G protein signaling family with the long splice variant of type 5 G protein beta subunit (RGS9.Gbeta5L). However, physiologically rapid GTPase is observed only when transducin forms a complex with its effector, the gamma subunit of cGMP phosphodiesterase (PDEgamma). In this study, we addressed the mechanism by which PDEgamma regulates the rate of transducin GTPase. We found that RGS9.Gbeta5L alone has a significant ability to activate transducin GTPase, but its affinity for transducin is low. PDEgamma acts by enhancing the affinity between activated transducin and RGS9.Gbeta5L by more than 15-fold, which is evident both from kinetic measurements of transducin GTPase rate and from protein binding assays with immobilized transducin. Furthermore, our data indicate that a single RGS9.Gbeta5L molecule is capable of accelerating the GTPase activity of approximately 100 transducin molecules/s. This rate is faster than the rates reported previously for any RGS protein and is sufficient for timely photoreceptor recovery in both rod and cone photoreceptors.

Quantitative sensory studies in complex regional pain syndrome type 1/RSD.

OBJECTIVE: Patients with complex regional pain syndrome type I (CRPSD1) may have thermal allodynia after application of a non-noxious thermal stimulus to the affected limb. We measured the warm, cold, heat-evoked pain threshold and the cold-evoked pain threshold in the affected area of 16 control patients and patients with complex regional pain syndrome type 1/RSD to test the hypothesis that allodynia results from an abnormality in sensory physiology. SETTING: A contact thermode was used to apply a constant 1 degrees C/second increasing (warm and heat-evoked pain) or decreasing (cold and cold-evoked pain) thermal stimulus until the patient pressed the response button to show that a temperature change was felt by the patient. Student t test was used to compare thresholds in patients and control patients. RESULTS: The cold-evoked pain threshold in patients with CRPSD1/RSD (p <0.001) was significantly decreased when compared with the thresholds in control patients (i.e., a smaller decrease in temperature was necessary to elicit cold-pain in patients with CRPSD1/RSD than in control patients). The heat-evoked pain threshold in patients with CRPS1/RSD was (p <0.05) decreased significantly when compared with thresholds in control patients. The warm- and cold-detection thresholds in patients with CRPS1/RSD were similar to the thresholds in control patients. CONCLUSIONS: This study suggests that thermal allodynia in patients with CRPS1/RSD results from decreased cold-evoked and heat-evoked pain thresholds. The thermal pain thresholds are reset (decreased) so that non-noxious thermal stimuli are perceived to be pain (allodynia).

Immobilized metal ion affinity chromatography on Co2+-carboxymethylaspartate-agarose Superflow, as demonstrated by one-step purification of lactate dehydrogenase from chicken breast muscle.

A rapid method for the purification of lactate dehydrogenase from whole chicken muscle extract in one chromatographic step is reported. The purification procedure can be accomplished in less than 1 h. A new type of immobilized metal ion affinity chromatography adsorbent is used that can be utilized at linear flow rates higher than 5 cm/min. The final preparation of the enzyme was with purity higher than 95% as ascertained by SDS-PAGE. Three immobilized metal ions (Ni2+, Zn2+ and Co2+) were compared for their binding properties towards the purified enzyme. The binding site of the enzyme for immobilized intermediate metal ions was determined after cleavage with CNBr and binding studies of the derivative peptides on immobilized Co2+. A peptide located on the N-terminus of the enzyme, implicated in the binding, has great potential as a purification tag in fusion proteins.

Natural poly-histidine affinity tag for purification of recombinant proteins on cobalt(II)-carboxymethylaspartate crosslinked agarose.

A natural 19-amino-acid poly-histidine affinity tag was cloned at the N-terminus of three recombinant proteins. The vectors containing the DNA of the fusion proteins were used for transformation of Escherichia coli DH5alpha cells. Each protein was expressed, extracted and purified in one chromatographic step. The purification procedure for each protein can be accomplished in less than 1 h. A new type of immobilized metal ion affinity chromatography adsorbent--Co2+-carboxymethylaspartate agarose Superflow--was utilized at linear flow-rates as high as 5 cm/min. The final preparation of each protein is with purity greater than 95% as ascertained by sodium dodecyl sulfate-electrophoresis. Recovery for each purified protein was higher than 77% of the initial loaded amount as judged by biological activity. The operational capacity of Co2+-carboxymethylaspartate agarose for each protein was determined.

AIDS risk among students attending Seventh-day Adventist school, in North America.

In 1995, a survey was conducted among students attending 69 Seventh-day Adventist (SDA) high schools within the United States and Canada. The survey assessed the extent that these students practiced sexual and drug-use behaviors which place them at risk for contracting or transmitting the human immunodeficiency virus (HIV). A total of 1,748 respondents enrolled in grades 9 through 12 completed questionnaires similar to the instrument used in the 1993 Youth Risk Behavior Survey (YRBS). Data were collected and compared to results from the 1993 YRBS. Students who attended SDA parochial schools reported lower rates of sexual intercourse compared to YRBS school counterparts (16.3% vs. 53.1%) and lower rates of all substances measured. Furthermore, respondents were more likely to engage in substance use and sexual intercourse if they had at least one parent who used tobacco, alcohol, or marijuana, as reported by the students.