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Biomedical subjects

M Pedersen

Publications and source records attributed to M Pedersen.

At least 55 records · Page 3Linked to original sources

Intratypic differentiation of poliovirus strains by enzyme-linked immunosorbent assay (ELISA): poliovirus type 2 and poliovirus type 3.

A double-antibody sandwich ELISA was developed for the detection of antigenic differences between wild and vaccine-derived strains of poliovirus type 2 and poliovirus type 3. Antibodies were prepared in rabbits by immunization with purified antigens of vaccine strains (type 2: Sabin P712, and type 3: Sabin Leon) and wild type strains (type 2: MEF, and type 3: Pool 30). Immunoblotting analysis of all antisera demonstrated that the IgG antibodies raised in rabbits have specificity towards the main structural proteins (Vp1, Vp2 and Vp3) of poliovirus. IgG fractions were purified from antisera by affinity chromatography, on a protein A-activated Sepharose 4B column. Purified IgG antibodies were used for coating of microtest plates (catching antibodies). The same reagents labelled with horseradish peroxidase were used as conjugates, after cross-adsorption with antigens of the same type heterologous virus strains (strain-specific conjugates). 29 poliovirus type 2 strains and 73 poliovirus type 3 strains isolated from clinical samples, were differentiated intratypically, as vaccine-derived or wild types, no intermediate strains were found and all samples tested fell in two distinct (vaccine/wild) categories. As little as 40 ng of poliovirus antigens was detected in stool samples from healthy children or from polio patients cultivated in monkey kidney tissue cultures. Preparation of strain specific conjugates did not require large amounts of poliovirus antigens. The developed ELISA, which is economic and capable of (1) detection of low amounts of poliovirus antigens in cultivated clinical samples, and (2) intratypic differentiation of poliovirus antigens as either vaccine-derived or wild type, is therefore well suited for large scale screening of poliovirus isolates.

Antibodies, Viral

SRS-A leukotrienes decrease the activity of human respiratory cilia.

We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured in a blind design by a microphoto-oscillographic technique. A total of 740 ciliated cells from seventy-four cell scrapings were studied. Mean baseline of ciliary beat frequency was 10.2 Hz. The ciliary beat frequency exhibited a pronounced variability in the spontaneous changes between the cell scrapings, yet less so within cell samples from the cell scrapings. We, therefore, evaluated the effect of the test solutions relative to the spontaneous decrease found during simultaneous perfusion with control solution of samples from the same cell scrapings. LTC4, 3-300 nmol/l, caused a highly significantly dose-related decrease in the ciliary beat frequency by up to approximately 20% as compared to the corresponding control solution. The effect of LTC4 was significantly inhibited by the SRS-A receptor antagonist FPL 55712 (10 mumol/l), but not by indomethacin (10 mumol/l). LTD4, 300 nmol/l, also decreased the ciliary beat frequency. LTB4, which is a leukotriene, although without the sulphidopeptide side chain of the SRS-A leukotrienes, did not affect the ciliary beat frequency in a concentration of 100 nmol/l. This would seem to confirm the structure specificity of the elucidated effect of the SRS-A leukotrienes. Histamine (100 mumol/l) did not affect the ciliary beat frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromones

Orchidectomy alone versus orchidectomy plus radiotherapy in stage I nonseminomatous testicular cancer: a randomized study by the Danish Testicular Carcinoma Study Group.

All Danish patients with stage I nonseminomatous testicular cancer diagnosed between December 1980 and January 1984 entered a randomized study comparing irradiation of retroperitoneal lymph nodes with surveillance only after orchidectomy. Twenty-four of the seventy-nine patients in the observation-only group have relapsed, three patients relapsing more than 2 years after orchidectomy. Ten of the seventy-three patients receiving irradiation have relapsed, all within 10 months after orchidectomy. The median time to relapse in both groups was 4.5 months. Irradiation prevented retroperitoneal relapses. Thirty-three of the relapsed patients were rendered disease free with chemotherapy, and one is still being treated. Four deaths have occurred, all unrelated to testicular cancer or antineoplastic treatment. Absence of embryonal carcinoma and presence of teratocarcinoma correlated with improved relapse-free survival. Patients with increased serum concentrations of tumour markers before orchidectomy had an increased risk of relapse. Surveillance-only is a reasonable treatment strategy in clinical stage I nonseminomatous testicular cancer. Preferably control and treatment of relapses should take place in specialized centres.

Carcinoma in Situ

Histamine release from basophil leukocytes induced by microbial antigen preparations in patients with AIDS.

Type I allergy against some common microorganisms was investigated in 14 patients with AIDS and 11 human immunodeficiency virus (HIV) antibody-positive homosexual men, and in a control group consisting of 13 heterosexual men without HIV antibodies. Basophil histamine release technique was used as a sensitive method to detect type I allergy against Candida albicans (CA), Herpes simplex virus type I (HSV-I) and cytomegalovirus (CMV). Of the 14 AIDS patients 11 (78%) showed significant histamine release when stimulated with CA, and HSV-I caused release in 10 (71%), whereas no response was obtained by CMV. In the group of HIV antibody-positive men only one released histamine when stimulated with CA and HSV-I and this patient also had lymphadenopathia. In contrast to these results, no release of histamine was obtained in the control group consisting of 13 heterosexual men. The histamine release caused by CA and HSV-I is mediated by an immunological reaction, since the release was abolished and regained by removal from and refixation to the cell surface of the cell-bound immunoglobulins. These results suggest an involvement of type I allergy as a pathogenetic co-factor in some infections in AIDS, and allergic type I reactions to CA and HSV-I might be an indicator for the presence of manifest AIDS.

Acquired Immunodeficiency Syndrome

Effect of N-acetylcysteine on the human nasal ciliary activity in vitro.

N-acetylcysteine (NAC) is widely used as a mucolytic agent, but the clinical and pharmacological effects of NAC are still unclear. It has recently been claimed in animal studies that NAC will stimulate ciliary beating frequency at low concentrations, while inhibiting beating at higher concentrations. Using a microphoto-oscillographic method combined with microperfusion technique, we studied the direct effect of NAC on human nasal cilia. NAC caused a direct dose- and time-related decrease in ciliary beating frequency, which was detectable at 2 mg/ml and reached statistically significant levels at 20 mg/ml. NAC at 200 mg/ml caused total cessation of movements within 15 s but this effect was completely reversible within 15 min of perfusion with medium alone. At no concentrations of NAC was beating frequency increased over base-line. NAC, however, had no effect on beating pattern. NAC seems to have a selective and fully reversible inhibitory effect on the beating frequency of human cilia in vitro.

Acetylcysteine

Postoperative radiotherapy in Dukes' B and C carcinoma of the rectum and rectosigmoid. A randomized multicenter study.

Results obtained during the first 5 years of a randomized study of postoperative radiotherapy (50 Gy) are presented. Criteria for randomization were fulfilled in 494 of 861 patients with Dukes' B and C tumors, when the trial was closed. Severe complications from radiotherapy approximated 10%. Probability of survival without local failure within 24 months was significantly higher after radiotherapy in patients with Dukes' C tumors, and the time of local failure was delayed 1 year. Patients with Dukes' B tumors had no benefit from radiotherapy. Risks of distant metastases and death were not influenced by radiotherapy in the main groups. Plasma-CEA measurements were evaluated blindly, and radiotherapy changed the critical levels of CEA for detection of recurrent cancer. It was concluded that patients with Dukes' C tumors may benefit from radiotherapy and plasma-CEA levels are influenced by radiotherapy, which may be important, when these are used in screening for recurrent cancer.

Actuarial Analysis

Spontaneous human meal patterns are related to preprandial factors regardless of natural environmental constraints.

There is a positive relationship between the amount people eat in a meal and the length of time since the previous meal (preprandial correlation). This study attempted to ascertain whether this correlation occurs due to environmental constraints on eating. Eight male and 30 female undergraduate students were instructed to list everything they ate and when they ate it. They were asked to make a recording in a diary of their eating and drinking throughout a 9 day period. They were also instructed to indicate whether the meal was spontaneous, in response to hunger or the desire for food, or constrained, determined by external factors. The amount of food energy in each meal was then calculated, and the amount remaining in the stomach at the beginning and end of each meal was estimated with a mathematical model. These data were then correlated with the duration of the intervals preceding and following the meals. The amount eaten in the meals was found to be predictable on the basis of preprandial factors regardless of whether the meal was initiated spontaneously or under environmental restrictions. Significant preprandial correlations were found for both constrained and spontaneous meals. No relationship was found between the amount ingested in the meal and the following interval (postprandial correlation) even when only the meals preceding a spontaneous meal were correlated. There were no significant correlations between the proportion of the meals that were constrained and the magnitude of either the preprandial or postprandial correlations. The findings suggest that humans initiate eating either in response to an externally determined schedule or to a learned schedule when constraints are not present.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Detection of specific immunoglobulin M to mumps virus in serum and cerebrospinal fluid samples from patients with acute mumps infection, using an antibody-capture enzyme immunoassay.

An immunoglobulin M (IgM) antibody-capture immunoassay using peroxidase-labelled mumps antibodies is described and its suitability for the practical diagnosis of acute mumps infection is evaluated. All 45 patients with confirmed mumps infection showed specific mumps IgM antibodies in their sera. Similarly, mumps IgM antibodies were detected in cerebrospinal fluid samples and sera from 12 patients with meningitis. Among these patients 8 had positive mumps virus isolates from the cerebrospinal fluid and 4 had not. Conversely, mumps IgM antibodies were detected neither in 418 serum samples from adult patients expected to be negative for mumps IgM, nor in 184 cerebrospinal fluid specimens from patients with various central nervous system symptoms, nor in sera from 10 patients with high levels of IgM-rheumatoid factor. Among 20 patients with respiratory illness caused by parainfluenza type-1 virus none showed an IgM mumps antibody response. In 99% of cases with acute mumps infection the IgM-ELISA gave a positive result in the first available serum samples most of which were negative for CF and mumps IgG antibodies. The virus proteins which take part in the IgM-ELISA test immune reaction are mainly the nucleoprotein and to a lesser extent the membrane protein. The IgM-ELISA method, which can be performed in 6 hours, offers a reliable, sensitive and rapid alternative to routine methods for the diagnosis of acute mumps infection.

Antibodies, Viral

Immediate and prolonged clinical efficacy of ceftazidime versus ceftazidime plus tobramycin in chronic Pseudomonas aeruginosa infection in cystic fibrosis.

20 patients with cystic fibrosis and chronic bronchopulmonary infection due to Pseudomonas aeruginosa entered a randomized cross-over study comparing ceftazidime (150 mg/kg body weight/24 h) plus tobramycin (10 mg/kg body weight/24 h) to ceftazidime alone (150 mg/kg body weight/24 h), both given intravenously for 2 weeks. 17 patients completed the study; both treatment regimens improved lung function and decreased the WBC count. No difference in clinical efficacy was found between the treatments. Pulmonary function returned to pre-treatment levels 3 months later with no difference between the treatments. No changes were seen in minimal inhibitory concentrations during treatment. None of the patients developed hypersensitivity or experienced serious adverse reactions to the drugs.

Adult

A comparative study of amoxycillin and pivampicillin in persistent Haemophilus influenzae infection of the lower respiratory tract in children with chronic lung disease.

A double-blind cross-over study was undertaken to compare the efficacy of amoxycillin and pivampicillin on Haemophilus influenzae infection of the lower respiratory tract in children. 20 patients with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD) due to other causes were included in the study. All patients had a history of regularly harbouring H. influenzae in sputum and repeated treatment failures with pivampicillin. 18 completed two 14-day courses in random order with equimolar doses of pivampicillin (80 mg/kg/day) and amoxycillin (62 mg/kg/day). Both drugs were well tolerated with no serious side effects, but pivampicillin was associated with more pronounced nausea. In steady state the mean serum concentrations of antibiotics 2 and 4 h after medication were 9.7 and 3.7 micrograms/ml for pivampicillin and 19.1 and 7.9 micrograms/ml for amoxycillin (p less than 0.01). Eradication of H. influenzae and clinical improvement was seen in one-third of the courses with both drugs. Betalactamase producing ampicillin-resistant strains emerged during 58% of the amoxycillin courses, but only in 16% of the pivampicillin courses (p less than 0.001). The high number of treatment failures and the development of resistant strains indicate that betalactamase inhibitors may possibly improve the efficacy of these drugs, especially of amoxycillin, in these patients.

Adolescent

Major or local surgery for cure in early rectal and sigmoid carcinoma--a prospective evaluation.

The results of different types of treatment for early cancer in 158 out of 1,300 patients with rectal and sigmoid cancer were evaluated in a prospective study from 1979 to 1984. Radical surgery was performed in 121 patients (mean age 66 years) with cancer Dukes' A (median diameter 3 cm), while 37 patients (mean age 71) with smaller cancers (median 2 cm) had polypectomy or local excision. Post-operative complications were significantly more frequent in the first group. No patients in any of the two groups with carcinoma in pedunculated adenomas or within the upper half of the submucosa or above 9 cm from the anal verge had recurrent cancer. CEA-measurements had no prognostic value. No difference was found in crude or cancer-related death between the two groups. The overall results support the use of local treatment in elderly patients with complicating disease, having small cancers, not penetrating the tunica muscularis externa of the rectosigmoid wall.

Adenoma