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Biomedical subjects

K Pedersen

Publications and source records attributed to K Pedersen.

At least 73 records · Page 4Linked to original sources

Clinical and economic considerations in the treatment of prostate cancer.

Prostate cancer is a growing health problem with considerable economic consequences. Despite progress in the management of this disease, few areas in medicine generate greater disagreement. The larger part of healthcare resources are allocated to 'halfway technologies' aimed at palliative intervention to prolong life, while a relatively small part goes to measures aimed at preventing or curing the disease. The aetiology of this cancer is multifactorial and no practical measures for primary prevention are known. The number of patients diagnosed with prostate cancer is increasing steadily. The age-adjusted mortality, however, has increased only slightly. In its early stages, prostate cancer is often asymptomatic and is usually not diagnosed until it has advanced. Programmes for the early detection of prostate cancer (screening) claimed to reduce morbidity and mortality are a matter of controversy. Furthermore, there has been much debate regarding optimal treatment in the early stages of the disease. Economic considerations have not as yet been integrated into studies concerning localised prostate cancer. The routine first-line treatment of advanced prostate cancer usually involves some type of endocrine treatment. The most straightforward technique is surgical castration. Oral estrogens are as effective as castration, but have significant cardiovascular adverse effects. These may possibly be prevented if estrogens are given parenterally. A third principal endocrine treatment is the administration of antiandrogens. Medical castration can be attained by the administration of recently developed synthetic peptides, gonadotrophin-releasing hormone {luteinising hormone-releasing hormone (LHRH)} (GnRH) analogue agonists which are given parenterally. The advantage of this type of medical castration is that the trauma of surgical castration and the adverse effects of oral estrogens are avoided. In an attempt to improve the results obtained with endocrine treatment, the concept of combining surgical or medical castration with antiandrogens was introduced. This combination could offer improved response rates and survival in a significant number of patients. However, this advantage must be weighed against the tolerability profiles and the high costs of antiandrogens and GnRH analogues. When using expensive drugs, the duration of treatment is a crucial factor in the total cost. As the length of treatment varies greatly between patients it is difficult to decide the most cost-effective alternative for a single individual. The patient's preference is an important factor when selecting treatment. When there is little or no difference in the effect of different regimens the total lifetime cost is important.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen Antagonists

Prostitution or sex work in the common market?

Prostitution has recently come under public and political scrutiny in the countries of the European Economic Community. A "pro-prostitution" lobby is promoting a program that portrays prostitution as sex work, which has provoked much debate. The author describes the debate, putting forward two paradigms of prostitution: the functionalist versus the socially critical views.

Denmark

Purification and characterization of IgM-like immunoglobulin from turbot (Scophthalmus maximus L.).

A total of 40 turbot (Scophthalmus maximus) were immunized 3 times during a 3 months period using DNP-HSA whereafter serum samples were collected and pooled. Specific immunoglobulins (Ig) were affinity purified on an agarose column with immobilized DNP-BSA and further purified by gel filtration whereafter monospecific rabbit anti Ig serum was generated. Size exclusion chromatography and non-reduced SDS-PAGE indicated a MW of 8-900 kDa of the dominant antigen binding proteins from turbot serum. Reduced SDS-PAGE showed this fraction to be composed of disulphide linked heavy and light chains with MWs of 79 and 27-29 kDa, respectively, indicating a tetrameric structure. Isoelectric focusing of the 800-900 kDa Ig showed several bands between pH 5.5 and pH 5.8. Mean Ig concentration in serum of 10 turbot was measured to 6.48 mg/ml (SD 5.4) using rocket immunoelectrophoresis. Low molecular weight antigen binding molecules were copurified with the dominating immunoglobulins with an estimated MW of 500 kDa. Reducing SDS-PAGE of this fraction revealed molecules with MWs of 97, 79, 57, 29, and 27 kDa.

Animals

[Meningoencephalitis after Mycoplasma pneumoniae infection].

A 15 year-old boy developed meningoencephalitis two weeks after onset of a respiratory tract infection caused by Mycoplasma pneumoniae. Central nervous complications are seen in 2-7% of patients hospitalized for M pneumoniae infection. Meningoencephalitis, meningitis, ataxia, polyradiculitis, psychosis and a few cases of apoplexy have been reported. In clinical practice one should be aware of M pneumoniae in the differential diagnosis of patients with suspected microbiologically induced central nervous complications. The pathogenetic aspects and prognosis are briefly discussed.

Adolescent

[Serology in patients with scleroderma].

In order to evaluate the practical clinical value of centromere, Scl-70, and nucleolar antibodies as demonstrated routinely by the Autoimmune Department of the Serum Institute of Copenhagen, 1293 sera from 497 patients with scleroderma (SSc) and other connective tissue diseases were tested for the three antibodies and for other nuclear antibodies. The three antibodies were found in 32, 15 and 15%, respectively, of sera from patients with SSc. Since more than one of the three antibodies was rarely demonstrated in any one serum, one of them was found in two thirds of sera from patients with SSc. The specificity of the three antibodies for SSc was 95% or more. Centromere antibody was found most frequently in patients with limited SSc. Scl-70 antibody was found almost exclusively in sera from patients with extensive SSc (involving the skin of the trunk). In such sera, centromere antibody was found in only 21%. Scl-70 antibody was overrepresented and centromere antibody was underrepresented in sera from patients with pulmonary involvement, the converse being true for sera from patients with calcinosis, esophageal involvement and telangiectasia.

Antibody Specificity

Phylogeny and phenotypic characterization of the stalk-forming and iron-oxidizing bacterium Gallionella ferruginea.

The 16S rRNA gene of Gallionella ferruginea was amplified by polymerase chain reaction and sequenced by direct double-stranded sequencing. The phylogenetic analysis placed G. ferruginea in the beta-group of the Proteobacteria, with 90.0% similarity to Nitrosolobus multiformis and 88.6% to Rhodocyclus purpureus. The published phenotypic characteristics of G. ferruginea were compiled and supplemented with growth experiments using ferrous iron, thiosulphate and sulphide as electron donor, and nitrate as nitrogen source. G. ferruginea is a Gram-negative, curved bacterium with one polar flagellum. It grows auto- and mixotrophically with CO2, glucose, fructose and sucrose as carbon sources, ferrous iron as an electron donor and ammonium or nitrate as nitrogen sources. Two G. ferruginea specific oligonucleotide probes are suggested. An iron-oxidizing bacterium without stalk-forming ability, but with the same growth pattern as G. ferruginea, was identified as G. ferruginea by comparison of highly variable parts of the 16S rRNA gene. This indicates that the stalk is not essential for growth.

Bacteria

Inter-observer variation in assessment of the prostate by digital rectal examination.

In a prospective study, inter-observer variation in the assessment of the prostate by digital rectal examination (DRE) by a urologist and a general practitioner was analysed. The 2 physicians performed independent assessment of the prostate in 933 men aged 50 to 69 years with regard to 9 variables as part of a screening programme for carcinoma of the prostate. Complete agreement for all observations was reached in 46.5% of the men. Using kappa (K) statistics, the values were adjusted for the expected chance agreement. K values between 0.485 and 0.682 were obtained for 6 variables representing good agreement; these were size, tenderness, midline furrow, symmetry, induration and nodularity. Agreement regarding fixation, lateral sulci and seminal vesicles was poor owing to the small number of cases deviating from normal. Contrary to the general belief that DRE is highly subjective, our results show a good correspondence between the observations of the examiners when assessing the prostate in a systematic way.

Aged

Neoadjuvant GnRH-agonist treatment (triptorelin and cyproterone acetate for flare protection) and total prostatectomy.

The effects of 3 months treatment with the GnRH agonist triptorelin as a neoadjuvant to total prostatectomy in 40 men with localized prostatic cancer have been evaluated. The study included 1 patient with a stage T1b tumour, 25 patients with stage T2 tumours and 14 with stage T3 tumours. The patients were examined by digital rectal examination, transrectal ultrasound before and after treatment. Serum testosterone and prostate-specific antigen (PSA) levels were followed. The totally removed prostate gland was step-sectioned at 5-mm intervals and the whole-mount sections were assessed for tumour pathology stage (pT stage). Triptorelin treatment resulted in a significant decrease in total gland and tumour volume and in a reduction in the serum levels of PSA and testosterone. In comparison with the findings from a previous study, in which neoadjuvant treatment was not used, it appears that the proportion of tumours invading the margins of the surgical specimen decreased.

Adenocarcinoma

Histopathological changes in androgen-deprived localized prostatic cancer. A study in total prostatectomy specimens.

Androgen deprivation with triptorelin treatment prior to total prostatectomy gave the opportunity of studying consequent morphological changes in the surgical specimens from 38 men with localized prostatic cancer. Multiple core-needle biopsies were taken prior to treatment and compared to the step-sectioned surgical specimens. The histological changes in the prostate following androgen deprivation include glandular atrophy, nuclear pyknosis, cytoplasmic vacuolation, squamous metaplasia and an increase in the relative amount of stroma. None of these changes could be correlated to pretreatment tumour grade, nor to the volume of the residual tumour. A positive correlation was found between tumour grade prior to therapy and volume of residual tumour after treatment. The treatment was not associated with downgrading of the malignancy. On the contrary, in 16% of the cases, foci of a higher grade were found in the surgical specimens compared to the pretreatment core-needle biopsies.

Biopsy, Needle

Efficient replication and expression of murine leukemia virus with major deletions in the enhancer region of U3.

The effect of deletions within the enhancer region in the U3 part of the LTR derived from the murine retrovirus Akv was studied. The deletions were stably transmitted through normal virus replication as shown by sequence analysis of cloned polymerase chain reaction product of the cDNA copy of the viral RNA. Genetic tagging of the retrovirus with lacO facilitated the analysis. Among the individual mutated LTRs an over 100-fold difference in a transient expression assay was previously detected. This difference was not revealed in studies of viral replication in cell culture, where the expression level of virus with the deleted LTRs all reached the level of virus with the intact LTR. We propose that stimulatory cis-acting sequences either adjacent to the site of proviral integration or in the coding regions of the provirus may compensate for deletions in the LTR.

3T3 Cells

Modulation of cholecystokinin (CCK) gene-expression in a human neuroblastoma cell line: effects of serum on enhanced CCK and c-fos mRNA expression.

The effect of fetal-calf serum (FCS) and Forskolin (FKN) on cholecystokinin (CCK) and proto-oncogene c-fos mRNA expression in the human neuroblastoma cell line SK-N-MC, cultured in serum free medium was studied by Northern blot analysis and nuclear run-off transcription analysis. Addition of FCS or FKN gradually increased the basal CCK mRNA level approximately four to six-fold after 2-4 h. In contrast, a strong and transient increase of the c-fos mRNA-level was observed, approximately forty to fifty-fold after 50-60 min over unstimulated cells. Nuclear run-off transcription analysis indicates that c-fos mRNA is constitutively expressed and transcription may be further stimulated by FCS and FKN. Moreover, in SK-N-MC nuclei, transcription of the c-fos gene clearly precedes stimulated CCK-mRNA expression. This suggests that FOS, which is known to form a AP-1 heterodimer transcription complex with the proto-oncogen product, Jun, may bind to the tentative AP-1 binding site, found within the human CCK promoter and thereby modulates basal and enhanced CCK-mRNA expression in SK-N-MC cells.

Base Sequence

Transfer of lactic acid bacterial strains from the feed to the sow, the environment, and the piglets.

The spread of lactic acid bacterial strains to the environment and to newborn piglets was investigated after feeding of such strains to sows. Rifampicin resistant bacterial strains were fed to sows, 10(10) c.f.u. per day, during the period from 1 week before expected farrowing until 1 week after farrowing. Fecal samples from the sows and samples of litter were collected for bacteriological examination together with swabs from the pens, the skin of the sows, and from the rectum of the piglets. The test strains were only excreted in relatively low amounts in the feces of the sows, approximately 10(3)-10(6) c.f.u. per gram. They were not able to displace the normal lactic acid bacterial flora in the sows nor were they transmitted to the intestinal tract of the piglets to any significant extent. After the last administration the test strains disappeared from both feces, skin, and environment, indicating that no permanent colonization had taken place, although considerable differences in duration of persistence were noticed between test strains.

Animal Feed

Lactic acid bacteria for mink. Colonization and persistence of Enterococcus faecium Cernelle 68 in the digestive tract of mink.

A method was developed to follow a lactic acid bacterial strain, Enterococcus faecium Cernelle 68, with respect to adhesion, multiplication, colonization, and persistence in the digestive tract of mink. Also the spread of the strain in the cage was examined. When adding 5 x 10(9) c.f.u. of a rifampicin resistant mutant per kg feed, high viable counts were registered throughout the digestive tract, apart from the oesophagus. Counts were increasing in the aboral direction, suggesting some multiplication in the intestine. It was possible to detect the strain in the intestinal tract 4 days after discontinuation of administration. Neither culture nor scanning electron microscopy gave evidence to suggest that E. faecium Cernelle 68 adhered to the mucosa. The spread of the E. faecium strain was observed in the environment. Counts of E. coli, lactobacilli, staphylococci, and clostridia were low, and none of these bacteria were constant findings.

Animals

Tagging the genome of the murine leukemia retrovirus SL3-3 by a bacterial lac operator sequence.

The bacterial lactose operator (lacO) was introduced into the PstI site of the long terminal repeat of the SL3-3 murine leukemia virus, generating a virus, SL3-3lacO, that can replicate in NIH3T3 cell cultures. DNA sequences harboring the lacO sequence might be recovered by molecular cloning in Escherichia coli lac+ lacZ+ using bacteriophage lambda or plasmid vectors. The high copy numbers of the lacO sequence titrate out the lac repressor, leading to the induction of the lac operon in the host. We show here that the lacO and the proviral sequences are carried stably together in the genomes of SL3-3lacO-infected cell cultures and in viral particles. This system is designed to facilitate studies on the provirus and the site of viral integration.

3T3 Cells