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Biomedical subjects

R Levi

Publications and source records attributed to R Levi.

At least 91 records · Page 5Linked to original sources
PubMed1995

Intranasal immunization of mice against influenza with synthetic peptides anchored to proteosomes.

Synthetic vaccines that are based on peptides representing immunogenic epitopes require a carrier molecule as well as an adjuvant in order to be effective. The choice of carriers or adjuvants approved for use in humans is very limited, and a considerable effort is devoted to develop new and efficient delivery systems. One of these vehicles utilizes preparations of outer membranes of meningococci, that form hydrophobic interactions, denoted proteosomes. Immunogenic proteins and peptides can be anchored to these proteosomes vesicles, which may serve as both carrier and adjuvant functions. In the present study we examined the ability of proteosomes to present epitopes of influenza, to elicit specific anti-influenza responses and to protect mice against viral challenge after intranasal immunization. Three influenza peptides were used--one corresponding to amino acid residues 91-108 of the haemagglutinin surface glycoprotein of H3 subtype, which comprises a B-cell epitope, and two from the internal nucleoprotein--a T-helper cell (Th) epitope (residues 55-69) and a cytotoxic T-lymphocyte (CTL) epitope (147-158). Mice were immunized intranasally (i.n.) with preparations containing each of the above epitopes, or various combinations thereof. The results obtained with this system demonstrate that influenza epitopes represented by synthetic peptides anchored to a proteosome carrier elicit both humoral and cellular specific immune responses, that can lead to partial protection of the mice from viral challenge. The importance of immunizing with vaccines containing both B- and T-cell peptide epitopes was emphasized by the demonstration that such vaccines elicited longer lasting immunity and led to more effective protection against influenza viral challenge.

Administration, Intranasal↗
PubMed1995

The Stockholm Spinal Cord Injury Study: 2. Associations between clinical patient characteristics and post-acute medical problems.

The Stockholm Spinal Cord Injury Study (SSCIS) is an extensive evaluation of a sample of 353 subjects with traumatic SCI, constituting 93% of the known regional prevalence population with this diagnosis. In a previous analysis of this group, symptoms such as pain, incontinence, sexual dysfunction and neurological deterioration, as well as secondary complications, such as decubitus ulcers, urinary tract infections, spinal deformity and fractures, were found to be common. In the present report, we investigate associations between a few commonly used patient characteristics, ie gender, age at injury, duration of injury and extent of neurological compromise, and the occurrence of such problems, to assess differences in vulnerability in SCI subgroups. Results generally indicate an increased vulnerability in subjects with extensive neurological deficits, as well as a cumulation of complications with the increasing duration of injury. However, some exceptions are found, possibly indicating differences in temporal patterns of the occurrence of various complications, as well as certain gender-, age-, and lesion-associated variations in vulnerability. Symptoms directly related to the spinal cord lesion, eg neurogenic pain and neurological deterioration, seem to present rather soon post-injury. Males are more prone to experience excessive spasticity and sexual problems. Females experience more fractures and spinal deformity. Younger age at injury is associated with more spinal deformity but less severe pain problems. Higher age at injury is not found to be associated with more medical problems, with the exception of neurogenic pain, among post-acute, post-discharge survivors. The latter finding does not, however, preclude more such problems in the acute stage, since the present study neither addresses the pre-discharge period, nor includes information about mortality. Finally, the ASIA/IMSOP Impairment Scale Grade E-rated subjects were found to report problems to an extent that underlines the restricted sensorimotor sense in which this rating reflects recovery.

Adult↗
PubMed1995

The Stockholm Spinal Cord Injury Study. 3. Health-related issues of the Swedish annual level-of-living survey in SCI subjects and controls.

In previous articles on the Stockholm Spinal Cord Injury Study (SSCIS), we have reported the frequent occurrence of medical problems in a near-total regional SCI population comprising 353 subject. This present study further investigates health-related issues in this SCI population, by a level-of-living survey that has been used annually on 8000-14,000 Swedes since 1974. The health-focused version of this survey was used for data collection in those 326 subjects in the SSCIS who were residents of the Greater Stockholm area. Subjects of the SSCIS living on the island of Gotland were excluded because they represented a sociodemographically different (rural) population. The normative material consisted of 1978 interviews of residents of the Greater Stockholm area, provided by the Swedish Bureau of Statistics. Results show a higher utilisation of health care resources among SCI subjects, shown by higher rates of long-term sick leave and sick pension, and more treatment as inpatients, emergency room attendees, and outpatients. Pain, bladder problems, and psychological symptoms are more commonly reported by SCI subjects. Medications such as antibiotics, analgesics, sedatives, hypnotics and laxatives are used more frequently in the SCI group. In contrast, no statistically significant differences were found as regards reported prevalence of diseases other than SCI, including diabetes, hypertension and cardiac disease. The results thus verify the impression from our previous studies of a clearly increased morbidity among these SCI subjects. The increased morbidity seems to be accounted for by the SCI itself, or conditions directly caused by it.

Adolescent↗
PubMed1995

The Stockholm spinal cord injury study: 1. Medical problems in a regional SCI population.

Out of a regional traumatic spinal cord injury population consisting of 379 individuals, 353 (93.1%) participated in the present study. Subjects were individually interviewed using semi-structured protocols. In addition, previous medical records were available for over 96% of subjects, and were used in all these cases to minimise recall bias. Cause of injury, prevalence of present medical symptoms and occurrence of medical complications in the post-acute, post-discharge phase were recorded. Neurological classification was verified by physical examination according to ASIA/IMSOP standards. Many subjects had experienced complications since discharge from initial hospitalisation, especially urinary tract infections, decubitus ulcers, urolithiasis, and neurological deterioration. Prevalence of medical symptoms was also high. More than 41% of subjects with spastic paralysis reported excessive spasticity to be associated with additional functional impairment and/or pain. Almost two-thirds of subjects reported significant pain, with a predominance of neurogenic-type pain. Bladder and bowel dysfunction were each rated by nearly 41% of subjects as a moderate to severe life problem. As expected, sexual dysfunction was also commonly reported. Prevalence of reported symptoms by general systems review was high, particularly fatigue, constipation, ankle oedema, joint and muscle problems, and disturbed sleep. However, lack of adequate normative data precludes comparison with the general population. The frequent occurrence of reported medical problems and complications support advocacy of comprehensive, life-long care for SCI patients. The commonly reported problems of neurogenic pain and neurological deterioration, in particular, require more attention, as these symptoms are not seldom ominous, either by virtue of their impact on quality of life, or because of underlying pathology.

Adolescent↗
PubMed1995

New aspects of the role of histamine in cardiovascular function: identification, characterization, and potential pathophysiological importance of H3 receptors.

As a result of intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H1 and H2 receptors are well known, whereas reports on the occurrence and function of H3 receptors in blood vessels and the heart have not become available before the last 7 years (i.e., 4 years after the first description of these receptors in the central nervous system in 1983). The development of selective and potent H3 receptor agonists and antagonists was a prerequisite for convenient investigations of cardiovascular H3 receptors, which like H1 and H2 receptors are G-protein coupled but unlike them have not yet been cloned. Both in blood vessels and the heart, H3 receptors are located on noradrenergic nerve endings and upon stimulation mediate an inhibition of noradrenaline release. Whereas it remains to be clarified under which conditions the vascular H3 receptors may be stimulated by endogenous histamine, those in the heart become activated in the early phases of myocardial ischemia characterized by an increased histamine spillover. The H3 receptors in the central nervous system also appear to be of importance for the control of vascular function. Inhibitory presynaptic H3 receptors occur on trigeminal sensory C fibres supplying blood vessels in the dura mater. Release of neuropeptides from these fibres induces a neurogenic inflammation, which has been suggested to be involved in the pathogenesis of migraine. An interaction, involving presynaptic H3 receptors, between sensory C fibres and mast cells in close apposition to these fibres plays a role in the control of histamine synthesis in the dura mater.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Differential hemodynamic effects of L-NMMA in endotoxemic and normal dogs.

We studied the differential hemodynamic effects of N omega-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthesis, in normal and endotoxemic dogs and examined its activity across the venous, pulmonary, and systemic circulations. Survival was used to determine therapeutic efficacy. In both normal and endotoxemic animals, L-NMMA similarly increased systemic (P = 0.01) and pulmonary (P = 0.047) vascular resistance, marginally increased mean arterial pressure (P = 0.07), and decreased oxygen delivery (P = 0.01) compared with normal saline. In contrast, the effect of L-NMMA on mean pulmonary arterial pressure, central venous pressure, and pulmonary capillary wedge pressure was different in endotoxemic than in normal animals (P < 0.05), but this differential effect occurred > 6 h after endotoxin challenge. L-NMMA (1-10 mg.kg-1.h-1) did not significantly increase survival rates or times in endotoxemic animals, but the highest dose decreased survival times (P < 0.05). Thus the effect of L-NMMA was similar on the systemic arterial circulation in endotoxemic dogs compared with normal dogs but was increased in the venous and pulmonary vascular beds after endotoxin, suggesting that the induction of NO production was greater in low-resistance vessels. We were unable to show that nonselective inhibition of NO production was beneficial in endotoxemic dogs.

Animals↗
PubMed1995

Synthetic recombinant vaccines against viral agents.

Synthetic recombinant vaccines are expression vectors incorporating defined epitope(s) of microbial agents. They are prepared by inserting synthetic oligonucleotide(s) coding for previously identified relevant epitopes into the genome of a desired vector, using recombinant DNA technology. The results discussed indicate that immunization with such vaccines carrying viral epitopes may lead to protective immunity against viral agents. Oligonucleotides coding for three influenza epitopes stimulating B cells, T helper cells and cytotoxic lymphocytes were individually inserted into the flagellin gene of a Salmonella vaccine strain. Immunization of mice with the resultant recombinant bacteria or their isolated flagella induced a specific mucosal anti-influenza protective response. The most efficient vaccine consisted of all three recombinant flagella, administered intranasally. The protection elicited was cross-strain specific, long-lasting and efficient against a lethal viral challenge.

Administration, Oral↗
PubMed1995

Protective role of bradykinin in cardiac anaphylaxis. Coronary-vasodilating and antiarrhythmic activities mediated by autocrine/paracrine mechanisms.

Cardiac anaphylaxis, an acute ischemic dysfunction comprising coronary vasoconstriction and arrhythmias, is a model of clinically recognized immediate hypersensitivity reactions affecting the heart. Bradykinin, a mediator of hypersensitivity, is also a potent coronary vasodilator, acting via nitric oxide and prostacyclin production. Because ischemia increases bradykinin outflow from the heart, we questioned whether bradykinin might mitigate anaphylactic coronary vasoconstriction. Antigen challenge of hearts isolated from presensitized guinea pigs was associated with an approximately 30% increase in bradykinin overflow. Furthermore, (1) when the half-life of bradykinin was prolonged with the kininase II/angiotensin-converting enzyme inhibitors captopril and enalaprilat, anaphylactic coronary vasoconstriction was attenuated and reversed, and arrhythmias were alleviated; (2) the bradykinin B2-receptor antagonist HOE 140 prevented these effects; and (3) HOE 140 exacerbated both anaphylactic coronary vasoconstriction and arrhythmias. During cardiac anaphylaxis, the coronary overflow of cGMP, a marker of nitric oxide production, and 6-ketoprostaglandin F1 alpha, a stable prostacyclin metabolite, increased two-fold and fourfold, respectively. Because neither enalaprilat nor HOE 140 affected these changes, the enhanced overflow of cGMP and 6-ketoprostaglandin F1 alpha is likely to reflect the actions of other hypersensitivity mediators (eg, histamine and leukotrienes). We postulate that bradykinin plays a protective role in cardiac anaphylaxis by accumulating at the luminal surface of the coronary endothelium and promoting, in an autocrine mode, a B2-receptor-mediated production of nitric oxide and prostacyclin in concentrations sufficient to elicit a paracrine effect on coronary vascular smooth muscle, thus opposing the vasoconstricting effects of other anaphylactic mediators.

Anaphylaxis↗
PubMed1995

Functional identification of histamine H3-receptors in the human heart.

Norepinephrine release contributes to ischemic cardiac dysfunction and arrhythmias. Because activation of histamine H3-receptors inhibits norepinephrine release, we searched for the presence of H3-receptors directly in sympathetic nerve endings (cardiac synaptosomes) isolated from surgical specimens of human atria. Norepinephrine was released by depolarization with K+. The presence of H3-receptors was ascertained because the selective H3-receptor agonists (R) alpha-methylhistamine and imetit reduced norepinephrine release, and the specific H3-receptor antagonist thioperamide blocked this effect. Norepinephrine release was exocytotic, since it was inhibited by the N-type Ca(2+)-channel blocker omega-conotoxin and the protein kinase C inhibitor Ro31-8220. Functional relevance of these H3-receptors was obtained by showing that transmural electrical stimulation of sympathetic nerve endings in human atrial tissue increased contractility, an effect blocked by propranolol and attenuated in a concentration-dependent manner by (R) alpha-methylhistamine. Also, thioperamide antagonized the effect of (R) alpha-methylhistamine. Our findings are the first demonstration that H3-receptors are present in sympathetic nerve endings in the human heart, where they modulate adrenergic responses by inhibiting norepinephrine release. Since myocardial ischemia causes intracardiac histamine release, H3-receptor-induced attenuation of sympathetic neurotransmission may be clinically relevant.

Cell Separation↗
PubMed1994

Hypoxic coronary vasodilatation and cGMP overproduction are blocked by a nitric oxide synthase inhibitor, but not by a guanylyl cyclase ANF receptor antagonist.

Myocardial hypoxia is known to be accompanied by the release of atrial natriuretic factor (ANF), a peptide which dilates the coronary vessels by stimulating particulate guanylyl cyclase. We have assessed whether ANF plays a paracrine role in hypoxic coronary vasodilatation, a reaction which we had previously found to be associated with increased cyclic GMP production. Compound HS 142-1 (100 micrograms/ml), a specific antagonist of the guanylyl cyclase ANF receptor, inhibited by 50-70% the coronary-vasodilating effects of human ANF (1-10 micrograms) administered to isolated guinea pig hearts, but affected neither hypoxic coronary vasodilation nor cyclic GMP overflow. In contrast, the nitric oxide synthase inhibitor N omega-methyl-L-arginine (300 microM) reduced hypoxic coronary vasodilatation and cyclic GMP overproduction by approximately 70% and 50-60%, respectively. Thus, unlike nitric oxide, ANF appears not to play a paracrine role in hypoxic coronary vasodilatation.

Amino Acid Oxidoreductases↗
PubMed1994

A computer assisted follow up system for spinal cord injury patients.

The comprehensive care of patients with traumatic spinal cord injuries (SCI) necessitates, among other things, a structured, life-long follow up. The high consumption of medical care in chronic SCI patients, often a result of diseases affecting many different organ systems, soon causes the cumulated medical documentation to be extensive and therefore hard to survey. The possibilities for rational patient management, adequate quality assurance, and clinical research may improve considerably by computerisation of medical records. A computerised medical records system for SCI has recently been developed, using a semistructured medical record format for data input and a medical entity dictionary for facilitated data storage and retrieval. The principles for developing this computer-assisted follow up system are described.

Humans↗
PubMed1994

Assisted ejaculation combined with in vitro fertilisation: an effective technique treating male infertility due to spinal cord injury.

Infertility due to spinal cord injury (SCI) in males has been identified for decades as an area of major concern and techniques for assisted ejaculation are available. There has not been an overall consensus regarding which type of assisted procreation is the most appropriate for these couples. We describe here our experience from a programme based on assisted ejaculation combined with in vitro fertilization (IVF). Twelve couples have been treated so far and altogether 22 cycles with ovum pick-up have been completed. Fertilisation of the oocytes was obtained in 18 of these cycles. The overall oocyte fertilisation rate was 49%. Embryo transfer took place in 17 cycles, leading to seven clinical pregnancies. Four of the pregnancies are delivered or are ongoing, whereas three ended in first trimester spontaneous abortion. Thus our initial experience suggests that assisted ejaculation in combination with IVF is an effective option for these couples.

Adult↗
PubMed1994

Motherhood after traumatic spinal cord injury.

The present study includes all women with a traumatic spinal cord injury in Sweden who became pregnant and delivered live infants during 1980-1991. This group comprises six tetraplegic and 20 paraplegic patients, all confined to a wheelchair. During the above mentioned period the patients had delivered a total of 47 children. The study evaluated parental ability and quality of family life as regards interpersonal relationships, family relationships, social integration, recreational interests and demand for external assistance. An individual standardised interview was performed with all patients. In addition a standardised questionnaire was sent to all spouses (n = 20) and to all children above 10 years of age (n = 10). All 26 patients participated, 18 spouses completed and returned the questionnaires and all children took part in the study. We found an overall favourable outcome as regards the parameters evaluated. The families seem to live a rich and complete family life with very little demand for external help. They report a well functioning social network and seem socially integrated both as individuals and as families. To conclude, the study indicates that there is no reason to question females with an SCI in their roles as parents. The spinal cord injury per se, in females, thus does not preclude the possibility of having a family and caring for children adequately.

Activities of Daily Living↗