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Biomedical subjects

R Levi

Publications and source records attributed to R Levi.

At least 19 recordsLinked to original sources

Transfer from table to wheelchair in men and women with spinal cord injury: coordination of body movement and arm forces.

STUDY DESIGN: A complex set-up was used to investigate kinematics and ground reaction forces. SETTING: Motor Control and Physical Therapy Research Laboratory, Neurotec Department, Karolinska Institutet, Huddinge, Sweden. OBJECTIVE: To investigate how men and women with spinal cord injury (SCI) perform transfers from table to wheelchair with regard to timing and magnitude of force generation beneath the hands and associated body movements. METHODS: A total of 13 subjects (seven men, six women) with thoracic SCI. Kinematics of body movement were recorded (Elite 2000 system) simultaneously with the signals from three force plates (AMTI) placed beneath the buttocks and hands. Temporal and spatial parameters regarding head, trunk and trailing arm displacement, loading amplitudes and loading torque directions of both hands were analyzed for each trial and subject and compared between genders. RESULTS: Men and women used similar amplitudes of head bending and forward displacement of the trailing shoulder, while female subjects had significantly larger trunk rotation. Both genders applied significantly more weight on the trailing hand. Differences between genders were seen in direction and timing of peak torque beneath the hands. CONCLUSIONS: The forces beneath the trailing hand were larger than those in the leading, if there is weakness or pain in one arm, this arm should be selected as the leading. To avoid excessive load on the arms, technical aids and environmental factors should be very well adapted. SPONSORSHIP: This project was funded by the Swedish Research Council and the Health Care Science Committee of Karolinska Institutet.

Adult↗

Pediatric spinal cord injury in a subset of European countries.

STUDY DESIGN: Postal survey. SETTING: A total of 19 countries in Europe. OBJECTIVES: Firstly, to collect information about incidence and systems of care for pediatric spinal cord injury (pedSCI); including prevention, initial care and follow-up in a subset of European countries. Secondly, to initiate a network of involved professionals for exchange of information and development of research and care programs. METHODS: A short semi-structured questionnaire was sent to respondents working with spinal cord injury (SCI) in 19 countries in Europe. RESULTS: Only in Portugal and Sweden, is the incidence of pedSCI (fatal injuries included) established, that is 27 children/million children/year and 4.6 children/million children/year, respectively. For the other countries, the estimated incidence of pedSCI (nonfatal injuries) varied from 0.9 to 21.2 children/million children/year in the age group of 0-14 years. Although the incidence varies considerably, pedSCI is rare throughout Europe. The management differs between the countries depending on the age of the child and the local organization of health care. CONCLUSIONS: The survey confirms that pedSCI is rare. In order to establish high-quality standardized care, further integration of knowledge in this area is needed throughout Europe. The contacts initiated by this survey may be used to create an international network serving as a reference for health professionals, researchers and families, thereby possibly alleviating some of the unwanted variations of care identified in this study.

Child↗

Indicators of psychological distress in postacute spinal cord injured individuals.

STUDY DESIGN: Consecutive inclusion of spinal cord injured patients admitted for postacute rehabilitation from June 2000 to January 2002. OBJECTIVE: Assessment of prevalence of indicators of psychological distress in the subacute and early chronic stages after acute-onset spinal cord injury (SCI). SETTING: A Swedish rehabilitation center. METHODS: In all, 36 patients participated. Psychological assessment was obtained at admission, discharge and 6 months follow-up by psychological measures based on the DSM-IV (ie Beck's Depression Inventory, SPIFA, SCID-screen, AUDIT) and clinical interview. Ongoing psychotropic medication was noted. RESULTS: Clinical depression was infrequent. However, ongoing psychotropic medication was common, possibly indicating a relatively high incidence of underlying depressive and anxiety disorders. In all, 25% of the sample showed indicators of high alcohol consumption. Few patients had a previously diagnosed personality disorder. By contrast, there was frequent occurrence of personality traits outside normal ranges. CONCLUSION: Medication of psychological problems commonly occurs after SCI, especially for depression and anxiety. There are indications of alcohol overconsumption in a substantial minority of SCI patients. The study raises the question of whether suppression of psychological symptoms by drug therapy is the optimal treatment of such problems in a rehabilitation process.

Adolescent↗

Cellular and molecular mechanisms of secondary hyperparathyroidism.

The objective of this review is to share important basic research insights into the mechanisms of secondary hyperparathyroidism. An understanding of these mechanisms is essential to more effectively treating the disease. Central underlying abnormalities are increased parathyroid hormone (PTH) gene expression and secretion, and parathyroid cell proliferation. Significant progress has been made in understanding these abnormalities at the cellular and molecular level, particularly their regulation. Studies point to a prominent role of calcium, phosphate and vitamin D as regulators of PTH and parathyroid cell proliferation. 1,25[OH]2 vitamin D3 decreases PTH synthesis and secretion. Small decreases in serum calcium and prolonged increases in serum phosphate as may occur in patients with chronic failure, increase PTH secretion, PTH gene expression, and parathyroid cell proliferation. Regulation at the level ofPTH gene expression is particularly significant given the limited amount of preformed mature PTH. It is now known that calcium and phosphate regulate PTH gene expression through changes in protective parathyroid cytosolic proteins that bind to an instability element in the PTH mRNA 3'-untranslated region and influence transcript stability. These findings may help guide the development of novel therapies for secondary hyperparathyroidism.

Calcium↗

Complete down-regulation is not mandatory for good assisted reproductive treatment cycle outcomes.

OBJECTIVE: To determine the implications and predictive value of estradiol concentrations following pituitary down-regulation with gonadotrophin releasing hormone agonists in women undergoing controlled ovarian hyperstimulation for assisted reproductive technology. STUDY DESIGN: A total of 277 patients undergoing ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI) were enrolled into the study and the patients were divided into four groups according to estradiol levels on the initial day of stimulation of which group-A consisted of the patients who had < or =25 pg/ml (n=90), group-B with levels between 26 and 50 pg/ml (n=104), group-C with levels between 51 and 75 pg/ml (n=67) and group-D with levels > or =76-90 pg/ml (n=16) and the results were compared. The primary outcome measures included ovarian response and the clinical pregnancy rates. RESULTS: The clinical pregnancy rates in groups-A, B, C and D were 33.3% (30/90), 26.0% (27/104), 35.8% (24/67), and 25.0% (4/16), respectively, and there was no statistically significant difference (P=0.482). The mean number of oocytes retrieved in groups were (9.7+/-5.8, 10.3+/-6.5, 11.0+/-6.8, and 12.1+/-6.6), respectively (P=0.453) and the fertilization rates in groups-A, B, C and D were found to be similar (75, 80, 73 and 79%, respectively; P=0.658). CONCLUSION: Complete and deep desensitization obviously seems not to be mandatory for successful stimulation in assisted reproductive technology cycles.

Adult↗

Dual sensory-motor function for a molluskan statocyst network.

In mollusks, statocyst receptor cells (SRCs) interact with each other forming a neural network; their activity is determined by both the animal's orientation in the gravitational field and multimodal inputs. These two facts suggest that the function of the statocysts is not limited to sensing the animal's orientation. We studied the role of the statocysts in the organization of search motion during hunting behavior in the marine mollusk, Clione limacina. When hunting, Clione swims along a complex trajectory including numerous twists and turns confined within a definite space. Search-like behavior could be evoked pharmacologically by physostigmine; application of physostigmine to the isolated CNS produced "fictive search behavior" monitored by recordings from wing and tail nerves. Both in behavioral and in vitro experiments, we found that the statocysts are necessary for search behavior. The motor program typical of searching could not be produced after removing the statocysts. Simultaneous recordings from single SRCs and motor nerves showed that there was a correlation between the SRCs activity and search episodes. This correlation occurred even though the preparation was fixed and, therefore the sensory stimulus was constant. The excitation of individual SRCs could in some cases precede the beginning of search episodes. A biologically based model showed that, theoretically, the hunting search motor program could be generated by the statocyst receptor network due to its intrinsic dynamics. The results presented support for the idea that the statocysts are actively involved in the production of the motor program underlying search movements during hunting behavior.

Action Potentials↗

Calcium signaling components of oscillating invertebrate neurons in vitro.

We have studied the Ca(2+) dynamics of bursting-spiking neurons in the lobster stomatogastric ganglion. Neurons in this ganglion undergo spontaneous oscillations in membrane voltage with a period of 1-10 s in situ. We found that neurons isolated from the ganglion and filled with the fluorescent calcium indicator Fluo-4 show simultaneous changes of membrane potential and cytoplasmic Ca(2+) concentration ([Ca(2+)](I)). These Ca(2+) signals are highly heterogeneous both in terms of amplitude and time constants. They showed variable spatial distributions with the soma exhibiting low and slow signals, and a region in the process with large and fast signals. Ca(2+) transients in the processes are dependent on external Ca(2+) and can be blocked by Co(2+), but not other, more specific Ca(2+) current blockers. Rather, nifedipine a known Ca(2+) current blocker, affects the distribution of the Ca(2+) signal, which suggests a specific localization of Ca(2+) channels. Although the signal is not absolutely dependent on action potentials, it is greatly reduced when action potentials are blocked by tetrodotoxin. Termination of the signal depends only slightly on Ca(2+) buffering mechanisms such as mitochondria, Ca(2+)/Na(+) and Ca(2+)/H(+) exchangers. We also demonstrate the presence of caffeine-sensitive internal stores in stomatogastric ganglion cells. The store distribution is different but overlaps with the voltage-dependent distribution. The maximal caffeine-activated Ca(2+) signal is in the soma and it is smaller in the processes. Unlike the voltage-activated Ca(2+) signal this signal is not blocked by Co(2+). Nevertheless, the two types of signal interact during caffeine application. This unique spatial separation of two Ca(2+) sources may have important functional implication.

Action Potentials↗

Gender related differences in pain in spinal cord injured individuals.

STUDY DESIGN: Out of a population of 456 patients with spinal cord injuries (SCI), 130 having pain were selected after matching, based on gender, age, American Spinal Injury Association (ASIA) impairment grade and level of lesion. OBJECTIVE: To investigate whether gender differences with regard to pain perception and prevalence exist in a population of patients following spinal cord injury. SETTING: Spinalis SCI Unit (out-patient clinic), Stockholm, Sweden. METHOD: 130 patients suffering from pain were assessed over a 12-month period in a yearly health control. RESULTS: SCI women had a higher prevalence of nociceptive pain than men and their use of analgesics was greater. However, no differences between the sexes could be seen regarding pain and localization, onset, distribution, factors affecting pain, number of painful body regions, pain descriptors, ratings of pain intensities or in pain and life satisfaction. CONCLUSION: This study showed that SCI men and women describe their pain very similarly. However, SCI women had a higher prevalence of nociceptive pain than men and their use of opiates and non-steroid anti-inflammatory drugs (NSAIDs) was greater.

Adolescent↗

Pediatric spinal cord injury in Sweden; how to identify a cohort of rare events.

STUDY DESIGN: Register study enhanced and verified by medical records and personal interviews and examinations. SETTINGS: Sweden. OBJECTIVES: To define a method of identifying a study population of rare events. To point out the relative importance of every step, an example is given of identifying persons who sustained traumatic spinal cord injury (SCI) in childhood. METHODS: Cases were identified in seven steps that all needed to be fulfilled, from definition of selection criteria through combination of several data sources, to the use of several verification methods. RESULTS: Initial screening by registers identified 384 possible cases, which however were found by subsequent analysis to include a large number of incorrect cases. At completion of all analytic steps, 35 living cases could be fully verified and 14 deceased cases could be partially verified. CONCLUSIONS: Registers offer a practical initial source for study population identification. The screening of International Classification of Diseases codes defining SCI only included less than 30% of 'true' SCIs. Subsequently, further refinement and quality control is necessary in order to ensure validity. Such further verification is time-consuming, but nevertheless necessary in order to verify a true cohort.

Child↗

Pediatric spinal cord injury in Sweden: incidence, etiology and outcome.

STUDY DESIGN: Retrospective descriptive study. OBJECTIVES: To assess incidence, causes and early outcome of traumatic spinal cord injury (SCI) among children in Sweden, thereby identifying high-risk groups and situations as a basis for preventative measures and improved care. METHODS: Data from population registers, County Habilitation Centers as well as from informal sources were used to estimate the incidence of SCI in Sweden during the years 1985-1996 among children aged 0-15 years. Contacts with the treating hospitals, reviews of medical records and/or personal interviews were used to verify primary data. In total, 92 children were thus identified. RESULTS: The incidence was found to be 4.6/million children/year (95% CI 3.6-5.5). When excluding prehospital fatalities, the incidence was 2.4 (95% CI 1.8-3.1). The main cause of injury among fatalities was traffic accidents. Associated injuries occurred in 41% of the children. Among survivors (10-15 years), sports-related injuries (43%) were as common a cause as traffic accidents (39%). The survivors were treated in 18 different hospitals. CONCLUSION: Pediatric SCI in Sweden is rare, presumably because of effective primary prevention. Preventative measures should be further differentiated for each age group of children in accordance with their differing risk profiles. In contrast to the effective preventative measures that have been implemented in Sweden, care of these patients is still too fractionated and decentralized for sufficient specialization to emerge.

Accidents↗

Heterologous cell-cell interactions: thromboregulation, cerebroprotection and cardioprotection by CD39 (NTPDase-1).

Blood platelets maintain vascular integrity and promote primary and secondary hemostasis following interruption of vessel continuity. Biochemical or physical damage to the coronary, carotid or peripheral arteries is followed by excessive platelet activation and recruitment culminating in vascular occlusion and tissue ischemia. Currently inadequate therapeutic approaches to stroke and coronary artery disease are a public health issue. Following our demonstration of neutrophil leukotriene production from arachidonate released from activated aspirin-treated platelets, we studied interactions between platelets and other blood cells, leading to concepts of transcellular metabolism and thromboregulation. Thrombosis has a proinflammatory component whereby biologically active substances are synthesized by interactions between different cell types that could not individually synthesize the product(s). Endothelial cells control platelet reactivity via three biochemical systems-autacoids leading to production of prostacyclin and nitric oxide, and endothelial ecto-ADPase/CD39/NTPDase-1. The autacoids are fluid-phase reactants, not produced by tissues in the basal state. They are only synthesized intracellularly and released upon interactions of cells with an agonist. When released, autacoids exert fleeting actions in the immediate milieu, and are rapidly inactivated. CD39 is an integral component of the endothelial cell surface and is substrate-activated. It maintains vascular fluidity in the complete absence of prostacyclin and nitric oxide, indicating that they are ancillary components of hemostasis. Therapeutic implications for the autacoids have not been compelling because of their transient, local and fleeting action, and limited potency. Conversely, CD39, acting solely on the platelet releasate, is efficacious in three different animal models. It metabolically neutralizes a prothrombotic platelet releasate via deletion of ADP--the major recruiting agent responsible for formation of an occlusive thrombus. In addition, solCD39 reduced ATP- and ischemia-induced norepinephrine release in the heart. This reduction can prevent fatal arrhythmia. Moreover, solCD39 ameliorated the sequelae of stroke in CD39 null mice. CD39 represents the next generation of cardioprotective and cerebroprotective molecules.

Adenosine Diphosphate↗

Controlled ovarian hyperstimulation and intrauterine insemination for infertility associated with endometriosis: a retrospective analysis.

OBJECTIVE: To evaluate the efficacy of controlled ovarian hyperstimulation and intrauterine insemination for infertility associated with endometriosis. MATERIAL AND METHODS: A retrospective analysis of 260 patients with the only diagnosis of endometriosis, or male factor, or tubal factor, or unexplained infertility were performed: a total of 56 patients with different stages of endometriosis, a control group consisting of 38 patients with male factor infertility, a group of 26 patients with tubal factor infertility and a group of 140 patients with others (unexplained infertility, ovulation disorders, cervical factor). Pregnancy rate, hormone levels, endometrial thickness and number of follicles were analyzed. RESULTS: Clinical pregnancy rates per patient were similar between endometriosis, male factor, tubal factor, and others including unexplained infertility, ovulation disorders and cervical factor groups (10.7%, 5.4%, 11.5%, 17.9%, respectively; p>0.05). Clinical pregnancy rates per patient were not effected between the 2 subgroups of endometriosis as minimal to mild and moderate to severe [5.1% (2/39) versus 23.5% (4/17), p=0.19]. CONCLUSION: Endometriosis did not affect the clinical pregnancy rate per patient compared to the other infertility factors. Endometriosis of various stages have no effect on the success of controlled ovarian hyperstimulation combined with intrauterine insemination.

Adult↗

Relationship of follicle number, serum estradiol level, and other factors to clinical pregnancy rate in gonadotropin-induced intrauterine insemination cycles.

OBJECTIVE: To determine the characteristics associated with clinical pregnancy rate after gonadotropin-induced intrauterine insemination cycles in patients without male or tubal factor infertility. MATERIALS AND METHODS: One hundred and eighty patients undergoing controlled ovarian hyperstimulation followed by intrauterine insemination were included in the study retrospectively. The patients' files were retrospectively evaluated with respect to age, number of follicles, endometrial thickness and serum hormone levels at baseline and at the day of human chorionic gonadotropin (hCG) administration. The patients with male or unilateral tubal factor infertility were excluded from the study. RESULTS: The serum estradiol level at the day of hCG administration was not correlated with the clinical pregnancy rate (r=-0.05, p=0.481). The number of follicles was not correlated with the clinical pregnancy rate (r=-0.09, p=0.209). There was no significant difference between the clinically pregnants (n=32) and not pregnants (n=148) regarding the mean age, baseline serum levels of luteinizing hormone (LH) and estradiol, serum estradiol and LH levels at the day of hCG administration and endometrial thickness (p>0.05). Although not statistically significant, a pregnancy rate of 14.2% with less than 3 follicles > or = 18 mm is present compared to a pregnancy rate of 27.5% with at least 3 follicles > or = 18 mm and 24% with > or = 4 follicles > or = 18 mm. CONCLUSION: The clinical pregnancy rate does not seem to be affected with the number of follicles present at the time of intrauterine insemination or the serum estradiol level at the day of hCG administration in a controlled ovarian hyperstimulation cycle in non-andrologic and non-peritubal factor infertility; however, there is a clear trend towards higher pregnancy rates with higher number of follicles.

Adult↗

Comparison of short and long ovulation induction protocols used in ART applications according to the ovarian response and outcome of pregnancy.

This retrospective study was designed to determine whether there is any difference between short and long protocol ovulation induction with Gonadotropin Releasing Hormone agonist (GnRHa) and gonadotropins used in Assisted Reproductive Technology (ART) applications according to the number of retrieved oocytes, oocyte maturity, fertilization rates, embryo quality and the outcome of pregnancies. 240 cycles consisting of in vitro fertilization (IVF) cycles without andrologic factor and intracytoplasmic sperm injection (ICSI) cycles were evaluated. 112 cycles which were induced by short protocol GnRHa and Follicle Stimulating Hormone (FSH) + Human Menopausal Gonadotropin (HMG) combinations and 128 cycles which were induced by long protocol GnRHa and FSH + HMG combinations were compared according to the number of retrieved oocytes, cancellation rate of cycles, oocyte maturity, fertilization rates, embryo quality and pregnancy rates. The cancellation rate for short protocol cycles were found to be significantly higher than those with long protocol. The number of retrieved oocytes, mature oocytes and fertilized oocytes were also found significantly lower. The quality of embryos did not show any significant difference between these groups. The clinical pregnancy rates were evidently found to be high in the long protocol cycles. As a conclusion we have found that while the number of retrieved oocytes, mature oocytes, fertilized oocytes and clinical pregnancy rates were increasing, the cancellation rate of cycles were decreasing significantly in ART cycles induced by long protocol.

Cell Count↗

Novel selective hypotensive vasopressin peptides: cardiovascular and structure-activity-relationship studies.

Recently, we discovered a series of peripheral acting selective hypotensive vasopressin peptides. Whether these peptides may interact with receptors outside the vasopressin receptor family and affect cardiac function could not be excluded. Accordingly, we tested the effects of these hypotensive vasopressin peptides on blood pressure and heart rate in intact rats and on the heart rate, ventricular contractile force and coronary flow of isolated perfused rat hearts. We found that the hypotensive vasopressin peptides did not modify cardiac function, either in vivo or in vitro. The vasodepressor potency was reduced when assayed in rats with vasopressin-maintained baseline blood pressure, suggesting that vasopressin and the hypotensive peptide compete for a common vasodilating vasopressin receptor in the vasculature. We have now synthesized more potent and radioiodinatable hypotensive peptides that could serve as lead compounds for the development of a radiomarker for the putative vasodilating vasopressin receptor.

Animals↗

Coupling of histamine H3 receptors to neuronal Na+/H+ exchange: a novel protective mechanism in myocardial ischemia.

In myocardial ischemia, adrenergic nerves release excessive amounts of norepinephrine (NE), causing dysfunction and arrhythmias. With anoxia and the concomitant ATP depletion, vesicular storage of NE is impaired, resulting in accumulation of free NE in the axoplasm of sympathetic nerves. Intraneuronal acidosis activates the Na(+)/H(+) exchanger (NHE), leading to increased Na(+) entry in the nerve terminals. These conditions favor availability of the NE transporter to the axoplasmic side of the membrane, causing massive carrier-mediated efflux of free NE. Neuronal NHE activation is pivotal in this process; NHE inhibitors attenuate carrier-mediated NE release. We previously reported that activation of histamine H(3) receptors (H(3)R) on cardiac sympathetic nerves also reduces carrier-mediated NE release and alleviates arrhythmias. Thus, H(3)R activation may be negatively coupled to NHE. We tested this hypothesis in individual human SKNMC neuroblastoma cells stably transfected with H(3)R cDNA, loaded with the intracellular pH (pH(i)) indicator BCECF. These cells possess amiloride-sensitive NHE. NHE activity was measured as the rate of Na(+)-dependent pH(i) recovery in response to an acute acid pulse (NH(4)Cl). We found that the selective H(3)R-agonist imetit markedly diminished NHE activity, and so did the amiloride derivative EIPA. The selective H(3)R antagonist thioperamide abolished the imetit-induced NHE attenuation. Thus, our results provide a link between H(3)R and NHE, which may limit the excessive release of NE during protracted myocardial ischemia. Our previous and present findings uncover a novel mechanism of cardioprotection: NHE inhibition in cardiac adrenergic neurons as a means to prevent ischemic arrhythmias associated with carrier-mediated NE release.

Animals↗

Value of serum CA-125 concentrations as predictors of pregnancy in assisted reproduction cycles.

The means by which endometrial receptivity influences conception rates in assisted reproductive technology (ART) is poorly understood. As the glycoprotein CA-125 is a product of human endometrium and is measurable in the peripheral circulation, it was investigated whether it might serve as an indicator of endometrial receptivity and predictor of pregnancy. In this prospective study, serum CA-125 concentrations of 75 ART cycles were measured 1 day before and on the day of human chorionic gonadotrophin (HCG) administration, and on the day of oocyte retrieval. These women did not have endometriosis and were induced by long-protocol gonadotrophin-releasing hormone analogue. Pregnancy was achieved in 35 (46.7%) cycles, but not in 40 cycles (53.3%). Serum CA-125 concentrations 1 day before and on the day of HCG administration and on the day of oocyte retrieval were significantly higher in cycles with pregnancy than in those without pregnancy (P < 0.05). It was noted that CA-125 concentrations on the day of oocyte retrieval were the best predictors of pregnancy, with concentrations >10 IU/ml having an accuracy of 86.6% for pregnancy. In conclusion, in intracytoplasmic sperm injection cycles, women with high serum CA-125 concentrations (>10 IU/ml) on the day of oocyte retrieval had very high pregnancy rates.

Abortion, Spontaneous↗

Unilateral ectopic twin pregnancy following an IVF cycle.

We report here a 37-year-old woman who underwent ovulation induction and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment because of infertility who developed vaginal bleeding at the 6th week of gestation. Abdominal ultrasonography was insufficient to distinguish the intrauterine gestational sac. Subsequently, vaginal doppler ultrasonography detected two separate unilateral twin ectopic pregnancies with cardiac activity in both fetuses, which were operated on pelviscopically.

Adult↗