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Biomedical subjects

L Stevenson

Publications and source records attributed to L Stevenson.

At least 19 recordsLinked to original sources
PubMed1998

Interactions between synthetic vanilloids and the endogenous cannabinoid system.

The chemical similarity between some synthetic agonists of vanilloid receptors, such as olvanil (N-vanillyl-cis-9-octadecenoamide), and the 'endocannabinoid' anandamide (arachidonoyl-ethanolamide, AEA), suggests possible interactions between the cannabinoid and vanilloid signalling systems. Here we report that olvanil is a stable and potent inhibitor of AEA facilitated transport into rat basophilic leukemia (RBL-2H3) cells. Olvanil blocked both the uptake and the hydrolysis of [14C]AEA by intact RBL-2H3 cells (IC50 = 9 microM), while capsaicin and pseudocapsaicin (N-vanillyl-nonanamide) were much less active. Olvanil was more potent than previously reported inhibitors of AEA facilitated transport, i.e. phloretin (IC50 = 80 microM), AM404 (12.9% inhibition at 10 microM) or oleoylethanolamide (27.5% inhibition at 10 microM). Olvanil was a poor inhibitor of [14C]AEA hydrolysis by RBL-2H3 and N18TG2 cell membranes, suggesting that the inhibitory effect on [14C]AEA breakdown observed in intact cells was due to inhibition of [14C]AEA uptake. Olvanil was stable to enzymatic hydrolysis, and (i) displaced the binding of high affinity cannabinoid receptor ligands to membrane preparations from N18TG2 cells and guinea pig forebrain (Ki = 1.64-7.08 microM), but not from cells expressing the CB2 cannabinoid receptor subtype; (ii) inhibited forskolin-induced cAMP formation in intact N18TG2 cells (IC50 = 1.60 microM), this effect being reversed by the selective CB1 antagonist SR141716A. Pseudocapsaicin, but not capsaicin, also selectively bound to CB1 receptor-containing membranes. These data suggest that some of the analgesic actions of olvanil may be due to its interactions with the endogenous cannabinoid system, and may lead to the design of a novel class of cannabimimetics with potential therapeutic applications as analgesics.

Animals↗
PubMed1998

Use of indomethacin for pain relief following scleral buckling surgery.

BACKGROUND/AIMS: Patients undergoing scleral buckling and cryotherapy suffer from mild to moderate postoperative pain. As good pain relief facilitates post-operative ocular examination, as well as patient comfort and recovery, the authors designed a prospective randomised double masked trial to evaluate the efficacy of indomethacin as a satisfactory analgesic for such patients. METHOD: Patients with a primary uncomplicated rhegmatogenous retinal detachment requiring scleral buckling and cryotherapy were randomly allocated to receive either indomethacin or placebo. A rectal suppository was administered 2 hours before surgery, followed by two capsules twice daily for 10 days. Pain relief was assessed with a linear graphic rating scale at the end of each day. Supplementary analgesia was allowed and recorded. RESULTS: 12 patients received indomethacin (group A) and 16 received placebo (group B). The extent of surgery was similar in both groups. One patient in group A, and two in group B withdrew after 3 days. The pain scores were converted to changes from the baseline (score on day 1), and the area under the curve calculated for each patient. The means of the areas were analysed with the Mann-Whitney test and showed that indomethacin caused a statistically significant reduction in pain score, both at 3 days (p = 0.04) and at 10 days (p = 0.014). There was no statistically significant difference in extra analgesic requirements between the two groups (p = 0.2). CONCLUSIONS: Indomethacin is recommended for short to medium term pain relief following scleral buckling and cryotherapy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Exercise in pregnancy. Part 1: Update on pathophysiology.

OBJECTIVE: To review the current data regarding the safety of exercise in pregnancy. QUALITY OF EVIDENCE: MEDLINE search was limited to English literature between 1987 and 1995 with the key MeSH words exercise and pregnancy. Other sources included the Sports and Fitness Database between 1991 and 1995 and a manual search for relevant articles. Previous studies on the safety of exercise in pregnancy are limited in many ways and exhibit difficulties in controlling for confounding factors and in establishing associations while maintaining maternal and fetal safety. MAIN FINDINGS: Concerns about the effect of exercise on pregnancy include exercise-induced hyperthermia, birth weight changes, fetal heart rate responses, miscarriage, labour patterns, maternal injury, and maternal weight gain. Exercise during pregnancy also has many potential benefits. CONCLUSIONS: Important gaps in our knowledge of exercise and pregnancy remain. Available data suggest, however, that moderate exercise on a regular basis during a healthy pregnancy has minimal risk for women and their fetuses.

Abortion, Spontaneous↗
PubMed1997

Exercise in pregnancy. Part 2: Recommendations for individuals.

OBJECTIVE: To provide practical guidelines for family physicians advising exercise in pregnancy. QUALITY OF EVIDENCE: MEDLINE search was limited to the English literature between 1987 and 1995 with the key MeSH words exercise and pregnancy. Other sources included the Sports and Fitness Database between 1991 and 1995 and a manual search for relevant articles. MAIN FINDINGS: After contraindications to exercise in pregnancy are excluded, the exercise prescription depends on the level of maternal fitness; the state of gestation; and the mode, intensity, duration, and frequency of exercise. Pregnant women must be closely monitored, particularly those who want to maintain vigorous exercise programs. CONCLUSIONS: The available data suggest that moderate exercise has minimal risk to a woman and her fetus, if the woman is in good health, the pregnancy is monitored, and the exercise program is modified as necessary.

Contraindications↗
PubMed1996

An induction gene trap screen in embryonic stem cells: Identification of genes that respond to retinoic acid in vitro.

We have developed a novel induction gene trap approach that preselects in vitro for integrations into genes that lie downstream of receptor/ligand-mediated signaling pathways. Using this approach, we have identified 20 gene trap integrations in embryonic stem cells, 9 of which were induced and 11 of which were repressed after exposure to exogenous retinoic acid (RA). All but one of these integrations showed unique spatially restricted or tissue-specific patterns of expression between 8.5 and 11.5 days of embryogenesis. Interestingly, expression was observed in tissues that are affected by alterations in RA levels during embryogenesis. Sequence analysis of fusion transcripts from six integrations revealed five novel gene sequences and the previously identified protooncogene c-fyn. To date, germ-line transmission and breeding has uncovered one homozygous embryonic lethal and three homozygous viable insertions. These studies demonstrate the potential of this induction gene trap approach for identifying and mutating genes downstream of signal transduction pathways.

Animals↗
PubMed1996

A targeted mouse Otx2 mutation leads to severe defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain.

Mouse Otx2 is a bicoid-class homeobox gene, related to the Drosophila orthodenticle (otd) gene. Expression of this gene is initially widespread in the epiblast at embryonic day 5.5 but becomes progressively restricted to the anterior end of the embryo at the headfold stage. In flies, loss of function mutations in otd result in deletion of pre-antennal and antennal segments; which leads to the absence of head structures derived from these segments. To study the function of Otx2 in mice, we have generated a homeobox deletion mutation in this gene. Mice homozygous for this mutation show severe defects in gastrulation and in formation of axial mesoderm and loss of anterior neural tissues. These results demonstrate that Otx2 is required for proper development of the epiblast and patterning of the anterior brain in mice, and supports the idea of evolutionary conservation of the function of Otd/Otx genes in head development in flies and mice.

Animals↗
PubMed1995

A novel regulatory region is required for trophoblast-specific transcription in transgenic mice.

The trophectoderm epithelium of the blastocyst is the first tissue to differentiate in the mammalian embryo and gives rise to all cells of the trophoblast lineage. These cells form the majority of the fetal component of the placenta, which is critical for intrauterine development. Our interest in the molecular determinants of trophoblast lineage development has led us to undertake an analysis of the regulatory region of a trophoblast-specific gene termed 4311. The transcription start site was mapped by both primer extension and RNase protection analyses. We show that cloned 4311 upstream sequences are able to confer the correct temporal and spatial expression pattern of 4311 on a reporter gene in transgenic mice. In addition, we have characterized a 340-bp region, 3.7 kb upstream of the transcription start, that is sufficient for the specific expression of lacZ in cells of the developing spongiotrophoblast in transgenic mice. Delineation of a diploid trophoblast-specific regulatory region will facilitate the identification of factors that may regulate the development of this lineage.

Animals↗
PubMed1994

Expression of the non-structural protein NS1 of bluetongue virus in bacteria and yeast: identification of two antigenic sites at the amino terminus.

cDNA transcribed from bluetongue virus serotype 1 (Australia) dsRNA 5 coding for non-structural protein NS1 was amplified in a polymerase chain reaction and ligated downstream of the T7 RNA polymerase promoter in the bacterial expression plasmid pET-5b, as a fusion protein with glutathione S-transferase using the pGEX bacterial expression system or the metallothionein promoter in the yeast expression plasmid pYELC5. The linear epitopes bound by six monoclonal antibodies to NS1 were localised to two antigenic regions at the amino terminus by Western blots using a series of carboxy-terminal truncations of the NS1 protein overexpressed in Escherichia coli. Expression of truncated NS1 genes using the pGEX expression system in E. coli enabled a more detailed map of the two epitopes to be constructed. The first epitope is thought to lie between amino acid residues 40-59, while the second is defined by the peptide sequences flanking amino acid 96.

Base Sequence↗
PubMed1994

Simultaneous bilateral trabeculectomy.

In a retrospective study, 24 patients who had undergone simultaneous bilateral trabeculectomy over a 6-year period were reviewed. The duration of disease was at least 2 years, indicating that surgery was not performed as a primary procedure. No patients suffered complications leading to bilateral blindness, although 6 (25%) patients had reduced vision in both eyes at the first postoperative visit, with 3 (13%) worse than 6/36 binocularly. There was no evidence of an asymmetric response in the fall in intraocular pressure following trabeculectomy, after a mean follow-up of over 3 years. Compared with a matched group of patients undergoing unilateral trabeculectomy, the simultaneous bilateral group had a similar period of hospital stay. However, this was no shorter than that found in a group having staged bilateral surgery during the same admission, over the same study period. When separate admissions were required for bilateral drainage operations, though, there was a significant increase in the total length of inpatient stay. No convincing advantage was found for simultaneous bilateral trabeculectomy.

Aged↗
PubMed1994

Increased effectiveness of interferon alfa-2b following active specific immunotherapy for melanoma.

PURPOSE: To determine whether interferon alfa-2b (IFN-alfa; intron-A, Schering Corp, Kenilworth, NJ) can induce a remission in patients previously treated with active specific immunotherapy (therapeutic melanoma vaccine) without response. PATIENTS AND METHODS: Eighteen patients with disseminated melanoma who had failed to respond to at least five injections of Melacine therapeutic melanoma vaccine (Ribi ImmunoChem Research, Inc, Hamilton, MT) were then treated IFN-alfa after a 4-week interval. IFN-alfa 5 or 6 x 10(6) U/m2 was self-administered three times a week subcutaneously by melanoma patients for at least 2 months. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging of the brain were performed within 4 weeks before treatment as a baseline, and then at 2-month intervals during treatment to evaluate response. All 18 patients were HLA-typed before treatment. The frequency of cytolytic T-cell precursors (pCTL) in the blood had been measured weekly in 13 of the patients during treatment with Melacine. RESULTS: Eight of 18 patients (44.4%) had a major objective clinical response induced by IFN-alfa, including site-specific complete remissions in five. Responses lasted a median of 11 months. The median survival duration of the responders has not been reached, and exceeds 32 months. The group as a whole had a median survival duration of 10.1 months, and nonresponders lived 7.3 months. Cytolytic T-cell precursors had been increased by immunization in all five responding patients tested, but also in five of eight nonresponders. There was no association of response to IFN-alfa with specific HLA phenotypes, in contrast to our previous results with melanoma theraccine alone. CONCLUSION: These data suggest an additive effect of active specific immunotherapy and IFN-alfa on the objective response rate, perhaps through upregulation of HLA molecules and tumor-associated antigens on the tumor cell by IFN-alfa, after immunization of the patient by Melacine. This treatment may have improved survival over that expected in metastatic melanoma.

Adult↗
PubMed1994

Improving cross-cultural skills of medical students through medical school-community partnerships.

Postulating that a program integrating language skills with other aspects of cultural knowledge could assist in developing medical students' ability to work in cross-cultural situations and that partnership with targeted communities was key to developing an effective program, a medical school and two organizations with strong community ties joined forces to develop a Spanish Language and Hispanic Cultural Competence Project. Medical student participants in the program improved their language skills and knowledge of cultural issues, and a partnership with community organizations provided context and resources to supplement more traditional modes of medical education.

Cross-Cultural Comparison↗
PubMed1993

The effect of colony age on PCR fingerprinting.

The pattern of DNA fragments produced by the polymerase chain reaction using arbitrary primers is strongly influenced by the age of the colonies sampled. We show that the number, clarity and reproducibility of the bands produced is optimal when very young colonies are sampled.

Bacteria↗
PubMed1992

Low-dose recombinant interleukin-2 and low-dose cyclophosphamide in metastatic breast cancer.

We undertook a preliminary study to examine the response rate of recombinant interleukin-2 (rIL-2) in patients with advanced measurable breast cancer, in a phase II clinical trial. The regimen we utilized was designed to allow outpatient administration. A treatment cycle consisted of low-dose cyclophosphamide (350 mg/m2) given on day -3 followed by the bolus administration of rIL-2 (3.6 x 10(6) Cetus units/m2) on days 1-5, and 8-12. Toxicity was significant but acceptable. One partial remission was seen in 13 evaluable patients. In 2 additional patients clear evidence of an antitumor response was observed. The study was terminated prematurely owing to a shortage of rIL-2. Additional evaluation of rIL-2 in breast cancer appears warranted.

Adult↗
PubMed1991

Gastrointestinal complications after cardiac transplantation: a spectrum of diseases.

Cardiac transplantation has become an accepted treatment modality for end-stage cardiac failure. The gastrointestinal (GI) tract represents a potential source of posttransplant morbidity and mortality. To define the scope of this problem, records of all patients undergoing cardiac transplantation at UCLA between January 1984 and July 1989 were reviewed. In all, there were 120 patients (90 males and 30 females) with a mean age of 45.4 yr. Among them, there were 61 patients (51%) who developed a total of 112 posttransplant GI complications. Of the entire 120 patients, 41 (34%) developed minor complications and 20 (17%) sustained major GI morbidity. Eighteen patients (15%) underwent either endoscopy or surgical intervention. These data suggest that most cardiac transplant recipients will experience some form of GI complication, although most are minor and can be managed conservatively. However, when major, life-threatening complications occur, evaluation and intervention should proceed expeditiously. The gastroenterologist and GI surgeon should play complimentary roles in the care of these complicated patients.

Adolescent↗
PubMed1990

Endothelial renin-angiotensin pathway. Adrenergic regulation of angiotensin secretion.

Cultured bovine aortic endothelial cells (BAECs) express the complete renin-angiotensin system and secrete angiotensins. In this study, we examined the adrenergic influence on the secretion of angiotensins from BAECs. Angiotensins were determined by high-performance liquid chromatography and radioimmunoassay. At basal state, BAECs contain angiotensin I, angiotensin II, and angiotensin III at concentrations of 2.5 +/- 1.3, 4.8 +/- 2.3, and 3.4 +/- 1.5 pg/10(6) cells, respectively. Angiotensin I, angiotensin II, and angiotensin III concentrations in the culture medium were 8.3 +/- 4.4, 9.4 +/- 3.5, and 9.9 +/- 3.3 pg/10(6) cells, respectively. Isoproterenol (0.1-10 microM) increases secretion of angiotensins I, II, and III in a dose-dependent manner. Increase in angiotensin secretion induced by isoproterenol (10 microM) can be inhibited by beta 2-adrenoceptor antagonist ICI 118,551 (1 microM), but not by beta 1-adrenoceptor antagonist atenolol (1 microM). Forskolin (1-1,000 microM) mimics the isoproterenol-induced response. In contrast, alpha-adrenergic agonist phenylephrine (1-100 microM) inhibits the secretion. Pretreatment of BAECs with captopril (1 microM) inhibits the accumulation of angiotensin II and angiotensin III in the culture medium, but not angiotensin I. These findings suggest that BAEC production and/or secretion of angiotensins is regulated by adrenergic mechanisms.

Angiotensin I↗
PubMed1990

Active-specific immunotherapy for melanoma.

Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.

Adjuvants, Immunologic↗
PubMed1978

The first derivative of the transthoracic electrical impedance as an index of changes in myocardial contractility in the intact anaesthetised dog.

The suitability of the peak value of the first derivative of the thoracic electrical impedance dZ/dtmax has been investigated in dogs as a non-invasive index of changes in myocardial contracility by comparing if with the peak left ventricular dP/dt and the peak values of aortic blood velocity and acceleration. An increase in the inspired halothane concentration was used to produce changes in contracility. In 5 dogs the combined values for the correlation coefficient between dZ/dtmax peak velocity and acceleration were respectively 0.937, 0.954 and 0.950. In 14 out 15 comparisons p less than 0.001 and in one, p less than 0.01. On these grounds, dZ/dt max is proposed as a variable worthy of sconsideration in patient monitoring.

Animals↗