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Biomedical subjects

R Levi

Publications and source records attributed to R Levi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Spasticity after traumatic spinal cord injury: nature, severity, and location.

OBJECTIVE: To assess spasticity in a prevalence population of persons with traumatic spinal cord injury (SCI), and determine the degree of correspondence between self-reported spasticity and investigator-elicited spasticity using the modified Ashworth scale. DESIGN: Survey of a near total (88%) prevalence population. SETTING: Outpatient clinic of a university hospital. PATIENTS: A total of 354 individuals with SCI. MAIN OUTCOME MEASURES: The survey includes self-reported symptoms, neurologic examination (American Spinal Injury Association [ASIA] classification), physical therapy examination, range of motion (ROM), and complications. RESULTS: Presence of problematic spasticity was significantly correlated with cervical incomplete (ASIA B-D) injury. Reports of beneficial effects of spasticity were significantly less common in women. Self-reported problematic spasticity was significantly correlated with extensor spasticity. Spasticity was elicitable by movement provocation in 60% of the patients reporting spasticity. Significant correlations were found between elicitable spasticity and limited ROM. CONCLUSION: Flexion, extension, and abduction movements performed with the patient placed in a standardized supine test position are suitable both for test of ROM and degree of spasticity. Spasticity was not elicitable by movement provocation on physical examination in 40% of the patients who reported spasticity, thus indicating that the patient's self-report is an important complement to the clinical assessment. A significant association between spasticity and contractures (reduced ROM) was seen.

Activities of Daily Living↗
PubMed1999

Norepinephrine release and ventricular fibrillation in myocardial ischemia/reperfusion: roles of angiotensin and bradykinin.

Exogenous bradykinin (BK), acting at B2-receptors, enhances norepinephrine (NE) release and exacerbates arrhythmias (VF) in myocardial ischemia/reperfusion. Inhibition of BK formation (with serine proteinase inhibitors) alleviates NE release and VF, whereas prevention of BK degradation (with kininase inhibitors) potentiates them. Yet serine proteinase and kininase inhibitors also prevent the formation of angiotensin (AII), a potent NE-release enhancer. Thus we assessed the respective contribution of AII and BK to NE release and VF by using selective B2- and AT1-receptor antagonists. Isolated guinea pig hearts were subjected to 10- and 20-min global ischemia and 45-min reperfusion. NE overflow (pmol/g) was approximately 8 (exocytotic) and approximately 750 (carrier mediated). VF, associated with carrier-mediated NE release, lasted approximately 2 min. The B2-receptor antagonist Hoe 140 (30 nM) affected neither NE overflow nor VF. In contrast, the AT1-receptor antagonist EXP3174 (100 nM) markedly reduced exocytotic and carrier-mediated NE release and shortened VF. When EXP3174 was combined with Hoe 140, NE overflow and VF were decreased even further. Thus in myocardial ischemia, local AII production contributes to NE release and VF via AT1-receptors. Although BK production increases in myocardial ischemia, the effects of BK on adrenergic nerve terminals are uncovered only when BK half-life is prolonged and/or when AII effects are suppressed.

Angiotensin Receptor Antagonists↗
PubMed1999

Bradykinin promotes ischemic norepinephrine release in guinea pig and human hearts.

We previously reported that bradykinin (BK; 1-1000 nM) facilitates norepinephrine (NE) release from cardiac sympathetic nerves. Because BK production increases in myocardial ischemia, endogenous BK could foster NE release and associated arrhythmias. We tested this hypothesis in guinea pig and human myocardial ischemia models. BK administration (100 nM) markedly enhanced exocytotic and carrier-mediated NE overflow from guinea pig hearts subjected to 10- and 20-min ischemia/reperfusion, respectively. Ventricular fibrillation invariably occurred after 20-min global ischemia; BK prolonged its duration 3-fold. The BK B2 receptor antagonist HOE140 (30 nM) blocked the effects of BK, whereas the B1 receptor antagonist des-Arg9-Leu8-BK (1 microM; i.e., 2.5 x pA2) did not. When serine proteinase inhibitors (500 KIU/ml aprotinin and 100 microg/ml soybean trypsin inhibitor) were used to prevent the formation of endogenous BK, NE overflow and reperfusion arrhythmias were diminished. In contrast, when kininase I and II inhibitors (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid and enalaprilat, each 1 microM) were used to prevent the degradation of endogenous BK, NE overflow and reperfusion arrhythmias were enhanced. B2 receptor blockade abolished these effects but was ineffective if kininases were not inhibited. B2 receptor stimulation, by either exogenous or endogenous BK, also markedly enhanced carrier-mediated NE release in the human myocardial ischemia model; conversely, inhibition of BK biosynthesis diminished ischemic NE release. Because atherosclerotic heart disease impairs endothelial BK production, in myocardial ischemia BK could accumulate at sympathetic nerve endings, thus augmenting exocytotic and carrier-mediated NE release and favoring coronary vasoconstriction and arrhythmias.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Bradykinin activates a cross-signaling pathway between sensory and adrenergic nerve endings in the heart: a novel mechanism of ischemic norepinephrine release?

We had shown that bradykinin (BK) generated by cardiac sympathetic nerve endings (i.e., synaptosomes) promotes exocytotic norepinephrine (NE) release in an autocrine mode. Because the synaptosomal preparation may include sensory C-fiber endings, which BK is known to stimulate, sensory nerves could contribute to the proadrenergic effects of BK in the heart. We report that BK is a potent releaser of NE from guinea pig heart synaptosomes (EC(50) approximately 20 nM), an effect mediated by B(2) receptors, and almost completely abolished by prior C-fiber destruction or blockade of calcitonin gene-related peptide and neurokinin-1 receptors. C-fiber destruction also greatly decreased BK-induced NE release from the intact heart, whereas tyramine-induced NE release was unaffected. Furthermore, C-fiber stimulation with capsaicin and activation of calcitonin gene-related peptide and neurokinin-1 receptors initiated NE release from cardiac synaptosomes, indicating that stimulation of sensory neurons in turn activates sympathetic nerve terminals. Thus, BK is likely to release NE in the heart in part by first liberating calcitonin gene-related peptide and Substance P from sensory nerve endings; these neuropeptides then stimulate specific receptors on sympathetic terminals. This action of BK is positively modulated by cyclooxygenase products, attenuated by activation of histamine H(3) receptors, and potentiated at a lower pH. The NE-releasing action of BK is likely to be enhanced in myocardial ischemia, when protons accumulate, C fibers become activated, and the production of prostaglandins and BK increases. Because NE is a major arrhythmogenic agent, the activation of this interneuronal signaling system between sensory and adrenergic neurons may contribute to ischemic dysrhythmias and sudden cardiac death.

Animals↗
PubMed1999

LLC-PK(1) cells stably expressing the human norepinephrine transporter: A functional model of carrier-mediated norepinephrine release in protracted myocardial ischemia.

In myocardial ischemia, adrenergic terminals undergo ATP depletion, hypoxia, and intracellular pH reduction, causing the accumulation of axoplasmic norepinephrine (NE) and intracellular Na(+) [via the Na(+)-H(+) exchanger (NHE)]. This forces the reversal of the Na(+)- and Cl(-)-dependent NE transporter (NET), triggering massive carrier-mediated NE release and, thus, arrhythmias. We have now developed a cellular model of carrier-mediated NE release using an LLC-PK(1) cell line stably transfected with human NET cDNA (LLC-NET). LLC-NET cells transported [(3)H]NE and [(3)H]N-methyl-4-phenylpyridinium ([(3)H]MPP(+)) in an inward direction. This uptake was abolished by the NET inhibitors desipramine (100 nM) and mazindol (300 nM) and by extracellular Na(+) removal. Na(+)-gradient reversal induced an efflux of (3)H-substrate from preloaded LLC-NET cells. Desipramine and mazindol blocked this efflux. Because of its greater intracellular stability and higher sensitivity to Na(+)-gradient reversal, [(3)H]MPP(+) proved preferable to [(3)H]NE as an NET substrate; therefore, only [(3)H]MPP(+) was used for subsequent studies. The K(+)/H(+) ionophore nigericin (10 microM) evoked a large efflux of [(3)H]MPP(+). This efflux was potentiated by the Na(+),K(+)-ATPase inhibitor ouabain (100 microM), was sensitive to desipramine, and was blocked by the NHE inhibitor 5-(N-ethyl-N-isopropyl)-amiloride (EIPA; 10 microM). In contrast, EIPA failed to inhibit the [(3)H]MPP(+) efflux elicited by the Na(+) ionophore gramicidin (10 microM). Furthermore, [(3)H]MPP(+) efflux induced by the NHE-stimulant proprionate (25 mM) was negatively modulated by imidazoline receptor activation. Our findings suggest that LLC-NET cells are a sensitive model for studying transductional processes of carrier-mediated NE release associated with myocardial ischemia.

1-Methyl-4-phenylpyridinium↗
PubMed1998

High antagonist potency of GT-2227 and GT-2331, new histamine H3 receptor antagonists, in two functional models.

GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and GT-2331 ((1R,2R)-4-(2-(5,5-dimethylhex-1-ynyl)cyclopropyl)imidazole) were developed as new potent histamine H3 receptor antagonists. The functional activity of these ligands on the histamine H3 receptor-mediated inhibition of neurogenic contraction of the guinea-pig jejunum and histamine H3 receptor-mediated inhibition of norepinephrine release from guinea-pig heart synaptosomes were investigated. GT-2227 and GT-2331 both antagonized the inhibitory effects of (R)-alpha-methylhistamine on the contraction induced by electrical field stimulation in the guinea-pig jejunum with pA2 values of 7.9+/-0.1 and 8.5+/-0.03, respectively. In addition, GT-2227 and GT-2331 antagonized the inhibition of norepinephrine release in cardiac synaptosomes by GT-2203 ((1R,2R)-trans-2-(1H-imidazol-4-yl)cyclopropylamine), a histamine H3 receptor agonist. The current results demonstrate the antagonist activity for both GT-2227 and GT-2331 in two functional assays for histamine H3 receptors.

Animals↗
PubMed1998

Simultaneous Ashworth measurements and electromyographic recordings in tetraplegic patients.

OBJECTIVE: A recent prevalence study of 353 spinal cord injured (SCI) individuals in the greater Stockholm area showed problematic spasticity in 30% of this population. To treat spasticity, the evaluation becomes crucial. The modified Ashworth scale (MAS) is the clinically most-used scale to grade degree of spasticity. This study evaluated whether the MAS correlated with electromyographic (EMG) recordings of muscle activity. STUDY DESIGN: This cross-sectional study was performed at an outpatient clinic that has the responsibility to do a standardized, yearly follow-up of all SCI patients in the greater Stockholm area. Thirty-eight SCI individuals met the inclusion criteria; 15 of the 38 were randomly selected for the study. They were all motor-complete tetraplegic men; mean age was 33 years and mean time since injury was 9 years. Spasticity evaluation was performed by flexing and extending the knees during simultaneous EMG recordings and MAS assessment of the thigh muscle activity. RESULTS: Eighty percent of the individual EMG recordings correlated significantly with the corresponding Ashworth measurements. The spastic resistance, as measured both clinically and electromyographically, was stronger and lasted longer during extension than flexion movements. Spearman coefficients for correlation of quantitative spasticity measures with MAS grades were calculated. EMG and clinical measures of spasticity were more closely correlated for flexion movements. Among EMG parameters, duration of movement-associated electrical activity invariably correlated significantly with the MAS grades (p < .05). Furthermore, Ashworth measurements of movement-associated spasticity showed a positive correlation with the EMG parameters mean, peak, and start to peak of electrical activity. Each increasing grade on the MAS corresponded to increasing myoelectric activity levels for each movement. CONCLUSION: EMG parameters were significantly positively correlated with simultaneous MAS measurements of the spastic muscle contraction. The Ashworth scale may therefore accurately reflect the movement-provoked spasticity in motor-complete tetraplegic patients.

Adult↗
PubMed1998

Quality of life and traumatic spinal cord injury.

OBJECTIVE: To determine associations between major outcome variables after traumatic spinal cord injury (SCI) and quality of life (QL). SUBJECTS: Of a total population of 353 SCI patients, 320 participated, 261 men and 59 women living in the greater Stockholm area: 124 were tetraplegic, 176 were paraplegic, and 20 had no classified level. Mean age was 42 years (range, 17 to 78). METHOD: The Swedish SF-36 Health Survey was used to assess QL. The SF-36 is a self-administered questionnaire containing 36 items, divided into 8 multi-item dimensions, covering physical function, physical and emotional role function, social function, bodily pain, mental health, vitality and overall evaluation of health. Neurologic, general medical, and psychosocial variables were obtained from the Stockholm Spinal Cord Injury Study (SSCIS) data base. QL indices were analyzed for the SCI group as a whole, as well as for subgroups. Descriptors for subgroups were demographic variables, presence or absence of common medical problems, and subjective evaluation of the degree of impact of the medical problem on well-being/daily activities. RESULTS: QL in individuals with SCI was significantly lower in all subscales as compared with a normative population. No difference in QL was seen in subgroups according to extent of lesion, with the exception of physical functioning. Several medical complications such as neurogenic pain, spasticity, and neurogenic bladder and bowel problems were associated with lower QL scores. SUMMARY: QL, as defined by SF-36, is better in persons injured many years ago, as compared with those recently injured, suggesting an adaptive process operating over a long period. The presence of complicating medical problems, such as severe pain, problematic spasticity, and incontinence, seem to have more negative effects on QL than the extent of SCI as such.

Adolescent↗
PubMed1998

Activation of influenza-specific memory cytotoxic T lymphocytes by Concanavalin A stimulation.

Traditionally, the in vitro activation of virus-specific memory cytotoxic T lymphocytes (CTLs) has been achieved by stimulating the CTLs with antigen-presenting cells (APCs) infected with an appropriate virus or pulsed with virus-specific antigenic peptides. Here, we describe the utilization of the polyclonal activator Concanavalin A (ConA) for in vitro restimulation of memory CTLs from virus-primed mice. Using this simple method, the activation of splenocytes with ConA for 3 days (i) eliminates the need to stimulate with virus-pulsed APCs and (ii) generates CD8+ CTLs that exhibit virus specificity and MHC-restricted lytic activity similar to CTLs obtained by conventional viral restimulation. In vitro ConA stimulation of splenocytes from BALB/c mice primed with the A/Texas/77 or A/Japanese/57 strain of influenza virus and from C57L/J mice infected with the A/Texas strain, generated CTLs with specific lytic activity. Hence reactivation of memory CTLs by this method is a general phenomenon rather than a mouse or viral strain-specific one. The ConA stimulation method used here had a recall of long-term (1 year) memory CTLs that effectively lysed virally infected targets. Further ConA-stimulated effector lymphocytes from virally primed animals have been shown to recognize and subsequently lyse target cells pulsed with virus or virus-derived peptides. The ConA reactivation of specific anti-viral CTLs may facilitate (i) studying anti-viral CTL responses and (ii) identifying of viral epitopes when unknown or when appropriate viral stimulation is impossible.

Animals↗
PubMed1998

Immuno-detection of aluminium and aluminium induced conformational changes in calmodulin--implications in Alzheimer's disease.

Binding of calcium to calmodulin (CAM) induces specific structural rearrangements in the whole protein molecule. Ca2+ organizes and stabilizes the four-domains structure of calmodulin in a helical, active conformation that can bind to its target proteins; the central helix remaining flexible is an essential condition for their bio-recognition. The conformation of calmodulin, and its efficacy to interact with target proteins, is profoundly altered when bound to metal ions other than calcium. As recently reported, the local structural changes of CaM, which occur upon aluminium binding, lead to the impairment of protein flexibility and to the loss of its ability to interact with several other proteins, which may decrease or inhibit the regulatory character of calmodulin. In this study we followed conformational changes occurring in the calmodulin molecule after aluminium binding using highly specific monoclonal antibodies (mAbs) able to differentiate between the conformational states of calmodulin, as well as mAbs which recognize aluminium free or bound to proteins. Under the same experimental conditions, mAb CAM-1, a Ca2+ conformation sensitive antibody raised against calmodulin, fails to recognize the calmodulin-aluminium complex, despite the presence of Ca2+, while the anti-Al antibodies show a maximal binding pattern towards their antigen. These data suggest that Al3+ ions bind to calmodulin in the presence of Ca2+ ions, leading to an inactive, reversible conformation, instead of its physiological active form. Alteration of the conformation of calmodulin imposed by Al binding may have possible implications in the neurotoxicity mechanism related to Alzheimer's disease.

Aluminum↗
PubMed1998

Obstructive sleep apneas in relation to severity of cervical spinal cord injury.

Thirty-three subjects (28 men, five women) with complete or incomplete cervical cord injury representing a wide range of neurological impairment were investigated with regard to the prevalence of Obstructive Sleep Apnea (OSA). The relation between OSA and neurological function, respiratory capacity, body mass index and symptoms associated with OSA were studied. Overnight sleep recordings employed combined oximetry and respiratory movement monitoring. Pulmonary function tests included static and dynamic spirometry, maximal static inspiratory and expiratory pressures at the mouth. The subjects answered a questionnaire concerning sleep quality and tiredness. The prevalence of OSA was 15% (5/33) in this nonobese cervical cord injury study population. Nine percent of the subjects (3/33) fulfilled the criteria for obstructive sleep apnea syndrome, but daytime sleepiness or fatigue were also common in subjects without OSA. There was an inverse correlation between oxygen desaturation index and American Spinal Injury Association (ASIA) motor score in the subjects with complete injury, while there was no such correlation in the whole study group. There were significant correlations between maximal inspiratory and expiratory pressures and vital capacity and between ASIA motor score and vital capacity.

Adult↗
PubMed1997

Obliteration of a posttraumatic spinal cord cyst with solid human embryonic spinal cord grafts: first clinical attempt.

Cystic lesions of the spinal cord (syringomyelia) may occur after spinal cord injury. Posttraumatic syringomyelia may result in a myelopathy causing symptoms of sensory and motor loss, as well as worsening spasticity, pain, hyperhidrosis, and autonomic dysreflexia. Shunting of the cyst cavity along with untethering of the scarred spinal cord is widely accepted as the treatment of choice. However, the long-term stabilization of the progressive myelopathy caused by a posttraumatic cyst is suboptimal because of arachnoidal rescarring, shunt tube blockage, and cyst reexpansion. A new neurosurgical strategy to overcome the complication of cyst reexpansion was designed. Experimental studies have shown the successful use of embryonic spinal cord grafts, including human grafts, to obliterate induced spinal cord cavities in rats. The authors report the first use of solid human embryonic spinal cord grafts to successfully obliterate 6 cm of a large cyst cavity in a patient becoming myelopathic from a posttraumatic cyst. The grafts are well visualized by MRI to the 7-month postoperative follow-up and cyst obliteration is seen in the region where the grafts were placed.

Fetal Tissue Transplantation↗
PubMed1997

Assisted ejaculation and in-vitro fertilization in the treatment of infertile spinal cord-injured men: the role of intracytoplasmic sperm injection.

The objective of the present longitudinal descriptive study was to extend previous observations on the benefit of in-vitro fertilization (IVF) in cases of anejaculatory infertility due to spinal cord injuries (SCI) and to report results achieved by intracytoplasmic sperm injection (ICSI). The study was performed in a national referral unit for SCI, Spinalis SCI Research Unit, the Karolinska Institute. The patient material consisted of couples with SCI men seeking treatment for their infertility. The inclusion criteria were: stable relationship, motile spermatozoa in a diagnostic sample and no female contraindications. Spermatozoa were retrieved through electroejaculation or vibratory stimulation. If the sperm quality was judged to be sufficient, standard IVF was performed. ICSI was employed if the semen quality was extremely poor. We have treated 25 couples in 52 cycles, leading to 81 ovum retrievals and 47 embryo transfers. Total sperm counts were very variable (0.01-978 x 10(6)). Before the introduction of ICSI the fertilization rate was 30%. ICSI increased the fertilization rate to 88%. There was no association between the pregnancy rate and the sperm count, level of injury or fertilization technique. A total of 16 clinical pregnancies was established, leading to 11 deliveries. This gives a cumulative pregnancy rate per couple of 56%.

Adult↗
PubMed1997

Bilateral femoral stress fractures in a child due to in-line (roller) skating.

We report a child who presented with a limp following 6 weeks of strenuous roller skating. Directed X-rays on admission were normal but a 99mTc-methylene diphosphanate bone scan demonstrated increased uptake in the mid-thirds of the femurs compatible with grade IV stress fracture. Immediate abstention from roller skating for 5 weeks resulted in a complete cure. The "new" side effect of this increasingly popular sport is discussed with regard to paediatric stress fractures and to other roller skating-associated injuries.

Child, Preschool↗
PubMed1997

Ischemic preconditioning prevents the impairment of hypoxic coronary vasodilatation caused by ischemia/reperfusion: role of adenosine A1/A3 and bradykinin B2 receptor activation.

We previously reported that hypoxic coronary vasodilatation (HCVD) is initiated by endothelial NO and sustained by adenosine. Prolonged ischemia/reperfusion impairs endothelium-dependent coronary vasodilatation, whereas transient ischemia (ie, preconditioning) protects the myocardium from subsequent ischemic events. Accordingly, we assessed whether prolonged ischemia/reperfusion impairs HCVD and whether preconditioning prevents this dysfunction. HCVD, elicited in isolated guinea pig hearts by a 1-minute exposure to 100% N2, consisted of an approximately 70% increase in coronary flow associated with enhanced nitrite/nitrate and adenosine overflow (+40% and 5-fold, respectively). After 30-minute global ischemia and 20-minute reperfusion, HCVD was decreased by approximately 60%, and the increases in nitrite/nitrate and adenosine overflow were abolished. Preconditioning (ie, three cycles of 5-minute global ischemia+5-minute reperfusion) prevented the impairment of HCVD and fully restored the increase in nitrite/nitrate overflow, but not that of adenosine. The protective effect of preconditioning was mimicked by perfusion with the adenosine A1 receptor agonist N6-cyclopentyladenosine and prevented by the A1 receptor antagonist N-0861. In addition, the A3 receptor agonist N6-(3-iodobenzyl)adenosine-5'-N-methyl-carboxamide had a similar protective effect. The bradykinin B2 receptor antagonist HOE 140 abolished the protective effect of preconditioning, whereas the NO synthase inhibitor N(omega)-methyl-L-arginine and the cycloxygenase inhibitor indomethacin did not. Our data indicate that preconditioning restores HCVD by a process that is triggered by activation of adenosine A1/A3 and bradykinin B2 receptors. The action of bradykinin is independent of NO and prostacyclin production. Once restored by preconditioning, HCVD is mediated by NO but no longer sustained by adenosine.

Adenine↗