[Familial hypercholesterolemia in children].
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Adolescent↗
Biomedical subjects
S Andersen
Publications and source records attributed to S Andersen.
The opioid ketobemidone has a NMDA blocking effect.
There are clinical observations that neurogenic pain can respond well to the opioid ketobemidone, in contrast to pethidine and morphine. This has led us to the hypothesis that the analgesic effect of ketobemidone in neurogenic pain may be due to both opioid as well as additional non-opioid effects. The present study was therefore made to evaluate the effects of ketobemidone. The study consists of two parts. (1) Single unit recordings were made from dorsal horn neurones in the halothane-anaesthetised rat. Neurones were activated by transcutaneous electrical stimulation of their receptive fields at C-fibre strength and their responses quantified. The wind-up of the neurones, due to N-methyl-D-aspartate (NMDA) receptor activation, leading to marked increases in C-fibre responses and an associated post-discharge was also measured. Ketobemidone, applied to the spinal cord, equivalent to an intrathecal injection, dose-dependently and selectively reduced C-fibre evoked responses. Ketobemidone was also found to block wind-up more effectively than morphine at equieffective doses, but unlike morphine in a non-naloxone-reversible manner. (2) In a binding study ketobemidone was shown to inhibit [3H]MK-801 binding with a Ki value of 26 microM. Therefore, ketobemidone appears to possess both mu opioid agonist as well as NMDA blocking effects.
Analgesics, Opioid↗
Phenotypic and genotypic characterization of phenanthrene-degrading fluorescent Pseudomonas biovars.
A total of 41 phenanthrene degraders were isolated from a former coal gasification site by using Pseudomonas-selective Gould's S1 medium. All isolates were found to belong to the fluorescent Pseudomonas group and were subjected to characterization by phenotypic methods, including classical taxonomic tests, API 20NE, and Biolog GN, and the strains were further characterized by the genotypic method repetitive extragenic palindromic PCR (REP-PCR). By using classical tests, the population was found to consist of 38 strains belonging to P. fluorescens, 2 P. putida strains, and 1 Pseudomonas sp. Bacteria in phenograms from Biolog GN and REP-PCR data were divided into groups, which were in good agreement with classical test and API 20NE results. We found a nonfluorescent group of 22 bacteria inconsistent with any Pseudomonas sp. in Bergey's Manual of Systematic Bacteriology. The group showed small differences in the genotypic test, indicating that all 22 isolates were not recent clones of the same isolate. Analyses of the nonfluorescent group indicated that it belonged to Pseudomonas, but the group could not be affiliated with P. fluorescens because of differences in DNA-DNA hybridization. Identifications using classical tests and API 20NE were found to correlate, but Biolog GN identifications after 24-h incubation resulted very often in the distantly related P. corrugata. The reproducibilities of individual tests of each phenotypic method were assessed, and low reproducibilities were mainly found to be associated with specific Biolog GN test wells. Classical tests and API 20NE proved to be the best for identification of isolates, whereas Biolog GN and REP-PCR were found to be the best tests for high resolution among these closely related isolates.
Bacterial Typing Techniques↗
Extracellular phospholipase A2 expression in sarcoidosis.
This study was conducted in order to focus upon the Ca2- dependent secretory non-pancreatic phospholipase A2 (npPLA2) enzyme and its possible role in the pathophysiology of sarcoidosis. Serum samples were taken from 24 patients with sarcoidosis to determine the levels of npPLA2. Moreover, in another group of patients with active chest x-ray stage II and III sarcoidosis, bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial lung biopsies (TBL) were taken. Highly significant increase of npPLA2 in serum was found in patients compared to controls (p < 0.001). Furthermore, those patients with stable and inactive disease and those who were under treatment with corticosteroids, tended to have lower values than those with active disease and those who were untreated. An intense accumulation of npPLA2 was found in smooth muscle tissue in lung biopsy specimens, in close connection with fibroblast accumulation and deposition of collagen. These cells also stained positive for alpha-smooth muscle actin (alpha-SMA). In addition, when using the technique of in situ hybridization, expression of npPLA2-mRNA was found in the fibroblast layer surrounding the epitheloid cell granulomas. These fibroblasts did not stain positive for alpha-SMA. Our data suggest that npPLA2 is actively involved, and has an important role, in the pathophysiology of sarcoidosis.
Actins↗
Management of chronic non-malignant pain.
Chronic non-malignant pain is often treated inadequately because of opiophobia. There is no scientific justification for this fear. With close monitoring and frequent controls, opioids are safe for this kind of pain. There is no scientific evidence that patients with chronic non-malignant pain are more prone to addiction or tolerance. It is also pertinent to consider that the endpoint of chronic pain treatment is not just freedom from pain but global wellbeing.
Analgesics, Opioid↗
[Opioids and receptor blocking].
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Analgesics, Opioid↗
Ketobemidone, methadone and pethidine are non-competitive N-methyl-D-aspartate (NMDA) antagonists in the rat cortex and spinal cord.
The opiate agonists, ketobemidone, methadone and pethidine, were evaluated as N-methyl-D-aspartate (NMDA) receptor antagonists using the rat cortical wedge preparation and the neonatal rat spinal cord preparation for electrophysiological studies and [3H](RS)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-im ine ([3H]MK-801) binding experiments using rat forebrain homogenates. Ketobemidone, methadone and pethidine were inhibitors of [3H]MK-801 binding with Ki values of 26 microM, 0.85 microM and 47 microM, respectively. In the cortex, 1 mM ketobemidone and 1 mM methadone reduced NMDA responses, but not (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA) or kainate responses in an use-dependent manner, whereas 1 mM pethidine was devoid of antagonist activity. In the spinal cord preparation, the activities of ketobemidone and methadone were weaker than in cortex. In contrast, pethidine was equipotent with ketobemidone in the spinal cord. These results suggest that ketobemidone and methadone may be useful therapeutic agents in conditions where a combined opiate agonist and NMDA antagonist treatment is desired.
Analgesics, Opioid↗
Prostate-specific membrane antigen: evidence for the existence of a second related human gene.
Prostate-specific membrane antigen (PSM) is a glycoprotein recognised by the prostate-specific monoclonal antibody 7E11-C5, which was raised against the human prostatic carcinoma cell line LNCaP. A cDNA clone for PSM has been described. PSM is of clinical importance for a number of reasons. Radiolabelled antibody is being evaluated both as an imaging agent and as an immunotherapeutic in prostate cancer. Use of the PSM promoter has been advocated for gene therapy applications to drive prostate-specific gene expression. Although PSM is expressed in normal prostate as well as in primary and secondary prostatic carcinoma, different splice variants in malignant tissue afford the prospect of developing reverse transcription-polymerase chain reaction (RT-PCR)-based diagnostic screens for the presence of prostatic carcinoma cells in the circulation. We have undertaken characterisation of the gene for PSM in view of the protein's interesting characteristics. Unexpectedly, we have found that there are other sequences apparently related to PSM in the human genome and that PSM genomic clones map to two separate and distinct loci on human chromosome 11. Investigation of the function of putative PSM-related genes will be necessary to enable us to define fully the role of PSM itself in the development of prostatic carcinoma and in the clinical management of this malignancy.
Antigens, Neoplasm↗
Gemcitabine: clinical and economic impact in inoperable non-small cell lung cancer.
This study assesses retrospectively the clinical and economic impact of gemcitabine monotherapy on the management of inoperable stage III/IV non-small cell lung cancer in Germany. Based on current methods of clinical practice and using the best outcome data available, the costs and benefits of gemcitabine were compared to a dual therapy (ifosfamide/etoposide). While the two treatments showed broadly equivalent efficacy in terms of tumour response rate and survival, a cost analysis showed the potential for savings with gemcitabine. These largely related to hospital hotelling costs, due to the fact that gemcitabine may be given as an out-patient therapy. Further savings were found in investigative procedures and the management of treatment toxicity. Excluding the cost of the chemotherapy, gemcitabine was associated with potential savings of DM3,026 over two cycles of therapy, which included a 40% decrease in hospitalization costs and a 54% decrease in the cost of managing adverse events. We conclude that gemcitabine monotherapy could offer considerable cost savings while offering the potential for improved quality of palliative treatment compared to existing in-patient treatments, and it may have a place in shifting care from an in-patient to an out-patient setting in line with recent health care reforms.
Antimetabolites, Antineoplastic↗
Measurement of palmitate availability in serum samples: method and utility.
Palmitic acid shows a very low and unknown solubility at neutral pH. Binding equilibria of palmitate to human serum albumin accordingly cannot be investigated by measuring free and bound ligand concentrations as in conventional binding studies. It is feasible, on the other hand, to describe the binding equilibria in relative terms, by measuring the concentration, p, of reserve albumin, previously defined as the concentration of a purified standard albumin preparation which in buffered solution binds a trace amount of palmitate as tight as it is bound in the sample. Palmitate availability is calculated as C/p, when C is the concentration of bound palmitate. The general binding equation is modified to contain the availability beside relative binding constants, Li = Ki/K1,St, where K1,St is the first stoichiometric binding constant for palmitate to the standard albumin preparation. Availabilities and relative binding constants can replace free concentrations and usual binding constants in considerations of biochemical transport and enzymatic mechanisms. A method is described for measuring the concentration of reserve albumin for binding of palmitate, based upon determination of dialytic exchange rates for palmitate among identical equilibrium samples. A technique for reproducibly adding radiolabelled palmitate to the samples is given.
Adult↗
[Congenital heart diseases in Sør-Trøndelag. Incidence, diagnosis, course and treatment].
In the county of Sør-Trøndelag, Norway, 145 children with congenital heart disease were detected among 14,194 live-born children from 1 January 1987 to 31 December 1990. This represents an incidence of 10.2 per thousand live-born children. The children were followed for six to 42 months (mean 2.38 years). Ventricular septal defect was detected in 71 (49%) cases. Isolated ventricular septal defect was found in 56 (39%) cases, the muscular type being the most frequent (three times that of the membranous type). Other congenital defects were found in 28 cases (19%), either as chromosome aberrations, syndromes or extracardiac malformations. 13 (9%) children died. None had constant symptoms of congestive heart failure by the end of the study. 34 (23%) cases were referred from mother and child clinics. 8 (5.5%) cases were detected prenatally. Compared with the results of other studies, the total incidence of congenital heart disease was high, and mortality and incidence of other coexistent congenital defects were low. It seems that small and less severe heart defects were detected more frequently in this study. The difference was most marked for incidence of muscular ventricular septal defect, atrial septal defect and pulmonary stenosis. The probable reasons for these results are an almost complete register of cases, well established postnatal care and a short distance to a pediatric cardiologist.
Child, Preschool↗
Elevated expression of human nonpancreatic phospholipase A2 in psoriatic tissue.
In involved psoriatic tissue, which is characterized by chronic inflammation in both epidermis and dermis, elevated levels of arachidonic acid and eicosanoids have been measured. This implies that a phospholipase A2 (PLA2) may be involved in the pathogenesis of psoriasis. The PLA2's are a group of enzymes that release unsaturated fatty acids from the sn2-position of membrane phospholipids. Once released, the fatty acids are converted by various enzymes into biologically very important signaling molecules. Release of arachidonate initiates the arachidonate cascade, leading to the synthesis of eicosanoids such as prostaglandins, thromboxanes, leukotrienes, and lipoxines. Eicosanoids are important in a variety of physiological processes and play a central role in inflammatory mediators, such as lyso-PAF (a precursor for PAF) and other lysophospholipids, may also be formed through the action of a PLA2. We report for the first time the detection of transcripts of nonpancreatic phospholipase A2 (npPLA2, type II) and cytosolic (c) PLA2 in human skin, and overexpression of npPLA2 in involved skin from patients with psoriasis (plaque psoriasis and pustular psoriasis). Limited amounts of npPLA2 enzyme are detected immunologically in the uppermost layers of epidermis from healthy persons. Both involved and uninvolved psoriatic epidermis contain higher levels of npPLA2 than normal skin. Positive cells in dermis showed significantly higher levels of npPLA2 than epidermal cells. In dermis from healthy persons, only weak staining of a few cells could be detected. The two PLA2 enzymes detected in psoriatic skin (cytosolic and nonpancreatic) may both be involved in eicosanoid overproduction in psoriatic tissue, and the npPLA2 may also be involved in potentiating cell activation, especially T cells.
Fibroblasts↗
Immunohistologic detection of non-pancreatic phospholipase A2 (type II) in human placenta and its possible involvement in normal parturition at term.
Placenta is one of the richest sources of non-pancreatic phospholipase A2 (npPLA2) (type II) in the human body, and the enzyme is the key enzyme releasing unsaturated fatty acids from membrane phospholipids. Prostaglandins (PGs) play a critical role in the initiation and progression of parturition. Cytokines are presumed to play a central role in the initiation of normal labor at term, and cytokines are also found to regulate both synthesis and secretion of npPLA2 enzyme. In an attempt to resolve the physiologic function of the npPLA2 enzyme in placental tissue, immunohistologic localization and enzymatic activity measurements of npPLA2 enzyme were performed. NpPLA2 protein was detected in vascular smooth muscle, endothelial cells and connective tissue cells in placenta and umbilical cord, and the protein was weakly stained in trophoblast cells in placenta. Enzymatic activity was not increased in sera from mother nor child compared to sera from healthy individuals, but the activity in amniotic fluid was considerably higher. Our findings support the candidacy for npPLA2 in enzymatic arachidonic acid release from foetal membranes.
Amniotic Fluid↗
[Rheumatic diseases. Discussion groups].
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Family↗
Street sale of heroin--a profitable way of making a living?
The aim of the study was to give an outline of the financial environment of heroin-sale at street level in Norway and the possibilities of making retail sale of heroin a living. Data were gathered through police records and interviews with informants at street level. Retail sale price has been nominally stable at 300 Nkr (28 pounds, i.e., 1 pound = 11 Nkr) per end-user dose since 1978. This price is coupled to the price of one standard service by street prostitutes. Both the end-users and retailers formally make their living from social welfare payments. The retailer purchases from a wholesaler batches of up to 10 g of heroin at a cost of 50,000 Nkr (4800 pounds). At monthly intervals of delivery this yields 120,000 Nkr (11,500 pounds) as net tax-free income per year, on top of the social welfare payments, even when the retailer and his accomplice consumes a third of the purchased quantity. Crime of gain on the part of the retailer is negligible, due to increased risk of also disclosing his drug trafficking.
Cost-Benefit Analysis↗
Drug addict rehabilitation: a burden on society?
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Adult↗
[Holiday town with premises for handicapped].
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Denmark↗
Multiple fatty acid binding to albumin in human blood plasma.
Binding equilibria of long-chain fatty acids to human serum albumin, in serum or plasma, were studied by a dialysis exchange rate technique. Palmitate was added to citrated plasma in vitro and it was observed that between six and ten palmitate molecules were bound to albumin with nearly equal affinity. Observations in vivo gave similar results in the following series: (a) in two volunteers with increased fatty acid concentrations after fasting, exercise, and a cold shower: (b) in three male volunteers in whom high concentrations of non-esterified fatty acids, up to 4.6 mM, were induced by intravenous administration of a preparation of lecithin/glycocholate mixed micelles, and (c) in 81 patients with diabetes mellitus, type I. The binding pattern of palmitate in serum or plasma is essentially different from that observed with palmitate added to buffered solutions of pure albumin when two molecules are tightly bound and about four additional molecules with lower affinity. The differences may partly be explained by the presence of chloride ions in blood plasma, reducing the affinity for binding of the first two fatty acid molecules, and partly by facilitated binding of several molecules of mixed fatty acids, as found in plasma.
Diabetes Mellitus, Type 1↗