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Biomedical subjects

C Svensson

Publications and source records attributed to C Svensson.

192 records · Page 11Linked to original sources

The effect of adenoidectomy on secretory otitis media: a 2-year controlled prospective study.

Seventy-eight preschool children considered to be suffering from long-standing secretory otitis media on the basis of a combination of impaired or abolished mobility of the tympanic membrane and conductive deafness, were examined consecutively. All children underwent bilateral paracentesis. Those children whose ears contained mucous secretion subsequently constituted a prospective longitudinal study group. On the same occasion as the paracentesis was performed, 24 children with bilateral or unilateral mucous secretion in their ears underwent adenoidectomy. Thirty-five non-adenoidectomized children with mucous secretion in one or both ears served as controls. Both groups were followed up for 24 months. At the end of this period they were compared with respect to the state and mobility of the eardrum, a pure tone average audiogram and middle ear impedance. No difference was detected between the two groups. It is therefore concluded that the preventive and therapeutic effects of adenoidectomy on secretory otitis media are doubtful.

Acoustic Impedance Tests↗

Thioridazine toxicity--an experimental cardiovascular study of thioridazine and its major metabolites in overdose.

Thioridazine, thioridazine side chain sulfoxide, side chain sulfone and ring sulfoxide were each given to two dogs in incremental doses. Profound changes in cardiac output and blood pressure were seen only in the dogs receiving the ring sulfoxide. Although all four drugs increased the QRS and Q-Tc interval, ventricular arrhythmias and "torsades de pointes" were seen only in dogs receiving the ring sulfoxide. Total plasma concentrations of thioridazine ring sulfoxide were in the same range as those seen in some patients on thioridazine therapy although the free concentrations were higher. Thioridazine ring sulfoxide appears to be the most toxic metabolite of thioridazine.

Animals↗

The diagnostic value of the hemoccult as a screening test in patients taking anticoagulants.

The value of a 3-day Hemoccult II test in the diagnosis of colorectal disease in patients receiving anticoagulant therapy was studied. The influence of rehydration and nonrehydration of the slide was investigated, as well as the reproducibility of positive tests. Eight hundred forty-nine patients on anticoagulant therapy performed three Hemoccult II tests each. One hundred twenty-eight (15%) had one or more positive slides, when these were rehydrated. Three patients with carcinoma and 13 patients with adenomas were found among these 128 patients. One hundred twenty-one of these patients performed six duplicate Hemoccult II tests with four samples from each of three consecutive stools. Three of the six slides were rehydrated and three were not rehydrated before development. Forty-one and 23 patients, respectively, showed positive test results. Two of three reinvestigated patients with large bowel carcinoma had positive slides in both of these series. Seven and 2, respectively, of 13 patients with adenomas had positive tests in the second series when the slides were developed with and without rehydration. Thus, the predictive value was low with nonrehydrated slides, and the precision was low when the slides were rehydrated. It is concluded that the sensitivity of a 3-day Hemoccult II test without rehydration is too low to permit its use as a screening method for colorectal neoplasms in patients receiving anticoagulant therapy.

Adenoma↗

Adenovirus 2 early region 1A stimulates expression of both viral and cellular genes.

The ability of products from the adenovirus early region 1A to stimulate viral and cellular gene expression has been studied, using a transient expression assay in HeLa cells. We show that the E1A 13S mRNA encodes a diffusible product which is capable of stimulating transcription of adenovirus genes as well as the rabbit beta-globin gene. The E1A 12S mRNA has no detectable stimulatory effect on either cellular or viral genes. Although being able to stimulate both types of genes, we find that the E1A regulatory protein enhances viral gene expression approximately 10 times more than beta-globin gene expression. We also find that when connected to the cis-acting SV40 enhancer element, the beta-globin gene cannot be further stimulated by the trans-acting E1A product. Finally, we find that transfection of either adenovirus or the beta-globin gene into 293 cells, which constitutively expresses the E1A gene products, leads to an enhanced expression which is 10- to 20-fold higher than obtained by co-transfection of HeLa cells. The 293 cells thus provide a simple assay to demonstrate E1A-mediated transcriptional regulation.

Adenoviruses, Human↗

Adenovirus VA RNAI: a positive regulator of mRNA translation.

We have developed a sensitive transient expression assay in 293 cells to study the effect of VA RNAs on the translation of adenovirus mRNAs. Monolayers of 293 cells were transfected with mixtures of recombinant plasmids encoding adenovirus-specific transcription units and plasmids encoding VA RNAs. Transfected cells were labeled with [35S]methionine for ca. 15 h, and labeled cell extracts were prepared. Changes in the protein expression caused by VA RNA cotransfection were measured by immunoprecipitation, using monospecific antisera prepared against adenovirus-specific polypeptides. Using this experimental design, we demonstrate that VA RNAI stimulates the translation of both early and late adenovirus mRNAs. Synthesis of the E3 19,000-dalton glycoprotein and the E2A 72,000-dalton DNA binding protein was stimulated between 10 and 20 times by VA RNAI cotransfection. Synthesis of the late hexon polypeptide was also stimulated, although translation of hexon was from an aberrant mRNA lacking the second and third segments of the common tripartite leader attached to late adenovirus mRNAs. VA RNAII, although very homologous to VA RNAI, does not function as a translational stimulator.

Adenoviruses, Human↗

Splicing of adenovirus 2 early region 1A mRNAs is non-sequential.

The r-strand of early region 1A (E1A) of adenovirus serotype 2 is transcribed into three completely overlapping messenger RNA species, a 9S, a 12S and a 13S mRNA. These three mRNAs are processed from a common colinear RNA precursor and differ only with regard to the size of the intron removed during mRNA maturation. We have studied the processing pathways for the E1A mRNAs by using an assay for transient expression of recombinant plasmids containing the E1A region. All three region E1A mRNAs are synthesized and transported to the cytoplasm in sufficient quantities to permit a detailed study of their structure by S1 endonuclease analysis and primer extension. Additionally, we show that the 72 base-pair repeat from simian virus 40 (SV40), when located upstream of the E1A promoter stimulates expression of the E1A mRNAs five- to tenfold. In order to determine whether splicing of the E1A mRNAs is sequential, i.e. whether the 13S and 12S mRNAs can serve as intermediates in splicing, we constructed two plasmids that lack the intervening sequences that are removed during the maturation of the 12S and 13S mRNAs, respectively. From an analysis of the RNAs produced after transfection with these deletion mutants, the following major conclusions can be made. (1) Splicing of the E1A mRNAs is non-sequential, i.e. the 13S, 12S and 9S RNAs are generated by separate splicing events using the nuclear colinear transcript as the only precursor RNA. (2) RNA splicing is not a prerequisite for an efficient transport of the E1A mRNAs to the cytoplasm. (3) The 13S RNA can be further processed to 12S and 9S RNA species. These splicing events are, however, illegitimate and give rise to 12S and 9S RNAs that both lack one nucleotide at the splice junction. (4) A coupling between splicing and nuclear transport is most likely required in vivo to prevent illegitimate splicing of the 13S mRNA. (5) The 12S RNA does not serve as a precursor for further processing to the 9S RNA. (6) Splicing of the E1A mRNAs followed strictly the G-T-A-G rule.

Adenoviruses, Human↗

Follow-up of patients with hereditary hemorrhagic telangiectasia in the nose, with special reference to septal dermoplasty.

Seventeen patients treated for recurrent epistaxis due to Osler's disease in the nose were followed up 6 months - 19 years after treatment. A written questionnaire was answered by 13 of the 14 patients surviving at follow-up. They had undergone either septal dermoplasty, or irradiation with 1200--1400 rad on both sides of the nose, or both kinds of treatment. All patients were satisfied with their treatment. The amount of nose-bleeding was reduced in all but one of the surgically treated patients, and the frequency was reduced in nine of the 13 patients. Nasal crusts, often causing nasal obstruction, were a problem, at least shortly after operation. Pathological vessels were found within the skin graft at secondary operation in one patient, showing that telangiectasia can develop in the graft area and cause recurrences of the epistaxis, sometimes necessitating further operations.

Adult↗

Concentration of penicillin in nasopharyngeal secretions.

The penicillin concentration in the nasopharyngeal secretion after penicillin administration was studied in 33 patients undergoing tonsillectomy. Benzylpenicillin was either administrated by the intravenous or the intramuscular route in doses of 0.6-1.2 g. Phenoxymethylpenicillin was given perorally in doses of 0.5-1.0 g. The secretion from the nasopharynx was collected prior to the operation both in a disposable collector and on a filter paper disc. A serum sample was also drawn prior to and immediately after the operation. The serum penicillin concentration reached levels of 16.0 mg/l, 5.8 mg/l and 3.6 mg/l (mean values) when given by the intravenous, the intramuscular and the peroral route, respectively. The mean penicillin concentration in nasopharyngeal secretion was 1.6 mg/l, 0.3 mg/l and 0.3 mg/l for these three administration modes. In the majority of cases the concentration of penicillin in the nasopharyngeal secretion exceeded the minimum inhibitory concentration for Streptococcus pneumoniae (0.006-0.12 mg/l).

Adolescent↗

Leader arrangement in the adenovirus fiber mRNA.

Four oligonucleotides, complementary to the adenovirus 2 (ad2) fiber mRNA were chemically synthesized and used as primers to study the 5' end of that messenger. The oligonucleotides which were 8, 10, 12, and 14 nucleotides long had a common 3'-terminal sequence, TAC, complementary to the initiating codon of the fiber mRNA. The 5'-32P-labeled oligonucleotides were hybridized to polyadenylated mRNA from ad2-infected cells and the primer was extended, using reverse transcriptase. When the resulting products were analyzed by polyacrylamide gel electrophoresis multiple distinct bands could be identified by autoradiography. The extension products were characterized by hybridization and sequence analysis. The most prominent band contained the well-known tripartite lead which is attached to many different late adenovirus mRNAs. In addition, four differently spliced leaders were characterized which, besides the three segments of the tripartite leader, contain one or two auxilliary segments. A kinetic analysis of the different leaders during lytic adenovirus infection shows no temporal variation.

Adenoviridae↗

Salivary duct carcinoma--a clinicopathologic study of 12 cases.

Salivary duct carcinoma (SDC), a recently defined malignant tumor usually of major salivary glands, has probably been included in the group of adenocarcinomas, NOS. As yet, only a few descriptions of its clinical behavior have appeared. We have found 12 cases of SDC treated at our institution since 1970 and have reviewed their presentation and course. Despite total parotidectomy in most cases and radiotherapy in all, most patients have succumbed to their tumors, six with distant metastases. SDC appears to be a highly malignant tumor requiring aggressive combined therapy for locoregional control. The high incidence of systemic spread indicates a need for effective chemotherapy on an adjuvant basis.

Adenocarcinoma↗

Nasal mucosal endorgan hyperresponsiveness.

Nonspecific hyperresponsiveness of the upper and lower airways is a well-known characteristic of different inflammatory airway diseases but the underlying mechanisms have not yet been satisfactorily explained. In attempts to elucidate the relation of hyperresponsiveness to disease pathophysiology we have particularly examined the possibility that different airway endorgans may alter their function in allergic airway disease. The nose, in contrast to the bronchi, is an accessible part of the airways where in vivo studies of airway mucosal processes can be carried out in humans under controlled conditions. Different endorgans can be defined in the airway mucosa: subepithelial microvessels, epithelium, glands, and sensory nerves. Techniques may be applied further in the nose to determine selectively the responses/function of these endorgans. Topical challenge with methacholine will induce a glandular secretory response, and topical capsaicin activates sensory c-fibers and induces nasal smart. Topical histamine induces extravasation of plasma from the subepithelial microvessels. The plasma exudate first floods the lamina propria and then moves up between epithelial cells into the airway lumen. This occurs without any changes in the ultrastructure or barrier function of the epithelium. We have therefore forwarded the view of mucosal exudation of bulk plasma as a physiological airway tissue response with primarily a defense function. Since the exudation is specific to inflammation, we have also suggested mucosal exudation as a major inflammatory response among airway endorgan functions. Using a "nasal pool" device for concomitant provocation with histamine and lavage of the nasal mucosa we have assessed exudative responses by analyzing the levels of plasma proteins (e.g., albumin alpha 2-macroglobulin) in the returned lavage fluids. A secretory hyperresponsiveness occurs in both experimental and seasonal allergic rhinitis. This type of nasal hyperreactivity may develop already 30 minutes after allergen challenge. It is attenuated by topical steroids and oral antihistamines. We have demonstrated that exudative hyperresponsiveness develops in both seasonal allergic rhinitis and common cold, indicating significant changes of this important microvascular response in these diseases. An attractive hypothesis to explain airway hyperresponsiveness has been increased mucosal absorption permeability due to epithelial damage, possibly secondary to the release of eosinophil products. However, neither nonspecific nor specific endorgan hyperresponsiveness in allergic airways may be explained by epithelial fragility or damage since nasal absorption permeability (measured with 51CR-EDTA and dDAVP) was decreased or unchanged in our studies of allergic and virus-induced rhinitis, respectively. Thus, the absorption barrier of the airway mucosa may become functionally tighter in chronic eosinophilic inflammation.

Blood Vessels↗