[Kartagener's syndrome in a sibling pair].
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Biomedical subjects
Publications and source records attributed to M Pedersen.
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In this study of intrinsic asthma (IA) in children the pathogenic role of bacteria in respiratory disease was elucidated by a basophil histamine liberation technique. Several strains of bacteria caused release of histamine from peripheral leukocytes in vitro. Normal, non-infectious and non-atopic children frequently responded in a similar fashion, although positive responses were less frequent. It seems that two different mechanisms of bacterial histamine release exist: interaction with the basophil-bound IgE and a direct interaction with the cell surface. It is suggested that the histamine release takes place only in the lung of IA patients, where a defective pulmonary barrier could permit the bacteria to enter, but not in healthy individuals.
The design, and complications seen during the first 2 years, of a randomized trial of postoperative radiotherapy for rectosigmoid cancer Dukes' B and C are presented and discussed. It is concluded that the present complication rate-below 10% in 221 patients-permits continuation of the intake, which is planned to include 550 patients, to demonstrate a possible increase in crude 5-year survival by 15% (60-75% in Dukes' B and 25-40% in Dukes' C), on the basis of a 0·01 significance level and a probability that the experiment will be successful of 0·90.
Ear, nose and throat symptoms and signs were studied in 15 patients with Kartagener's syndrome: a triad consisting of chronic rhinosinusitis, chronic bronchitis with bronchiectasis, and situs inversus. The triad is caused by primary ciliary dyskinesia and characterized by absent or considerably reduced mucociliary transport. Daily accumulation of secretions in the nose, chronic recurrent secretory otitis media and sinusitis occurred in all subjects. Characteristically, nasal discharge started at birth or was first detected in early childhood. Apparently, the frequency of common colds and of acute purulent otitis media was not increased. As primary ciliary dyskinesia can occur without situs inversus, knowledge of the typical ENT symptoms is essential for making an early diagnosis, which is important for the correct management of the disease. While a conservative surgical approach to treatment of the ENT symptoms is recommended, early and active treatment of the bronchial symptoms is probably important for prevention of further lung damage and development of bronchiectasis.
Twelve children, aged 4 to 14 years, with moderate to severe intrinsic asthma (IA) were studied. Symptom-Score charts were used to confirm the relationship of acute respiratory tract infections to exacerbations of asthma. Hypersensitivity to eight commonly occurring bacteria from the normal flora of the upper respiratory tract was studied by skin test, by crossed immunoelectrophoresis, and by basophil histamine release in vitro, using ultrasonicates of the bacteria as antigens. Skin tests were all negative. All children contained low titers of precipitating antibodies against most of the bacteria, but in this respect they did not differ from normal children. In contrast, release of histamine was induced in leukocytes from the IA children by all, or most sonicates, while such reactions, were less frequent in control children. The pattern of responses indicated an element of specificity. These was no correlation to precipitating antibodies, or to the microbial flora of the children. Positive responses were characterized by low values of maximal histamine release, and by a tendency to fluctuations with time. Because of these fluctuations, and because the IA children and control children were tested on separate occasions, we cannot be certain as to the real difference between these two groups. Our studies do, however, demonstrate that water-soluble constituents of all the bacterial strains tested were capable of causing the release of histamine in vitro, but that this phenomenon is not restricted to IA. The clinical significance of these findings awaits further investigations on the mechanism(s) of release in vitro by such agents.
A 2-year-old boy excreted massive amounts of formiminoglutamic acid in urine. The substance was identified as authentic formiminoglutamic acid by two-dimensional thin-layer chromatography, column chromatography and enzymatic determination. After alkaline hydrolysis the substance was converted to glutamic acid. Serum amino acid concentrations were normal. The patient had normal serum and erythrocyte folate levels. The red blood cell picture was normal. The leukocytes showed slight hypersegmentation. From the age of 3 months he exhibited recurrent otitis media and severe pulmonary infections. He had a peculiar narrow-headed look and marked universal hypotonia. The mental development was slightly retarded. Glutamate formiminotransferase deficiency is postulated. The findings lend support to the theory of glutamate formiminotransferase deficiency being a rather benign disorder of metabolism.
Arabinosyladenine, an established antiherpetic drug, was used to block herpes simplex virus type 1 DNA synthesis quantitatively in infected xeroderma pigmentosum cells. Kinetic analyses of viral polypeptides synthesized in the presence and absence of this drug revealed that there were at least six distinct kinetic classes of polypeptides. These differed in time of appearance after infection, time of maximum rate of synthesis, kinetics of turnoff, and sensitivity to arabinosyladenine. This study showed that arabinosyladenine had the following three main effects on herpes simplex virus type 1 gene expression. (i) The turnon of immediate early and delayed early polypeptides (kinetic classes 1 and 2) was retarded. (ii) The turnoff of early (immediate early and delayed early) polypeptides (classes 1 through 3) was delayed. (iii) The synthesis of late polypeptides (class 4 through 6) was inhibited by arabinosyladenine, with class 6 severely (80 to 90%) inhibited. The kinetic data presented here, along with the findings of other workers on the effects of inhibition of viral DNA synthesis, suggest that viral DNA replication is required for optimum synthesis of late viral polypeptides.
Our study was designed to examine the motility and ultrastructure of cilia from the nose of patients with Kartagener's syndrome. Microphoto-oscillographic recording from single cells showed that the patients had in fact motile cilia, although the number was reduced. Asynchrony within the single cell was a more consistent feature. The first results of blind, quantitative microscopy showed the ultrastructural defects, described earlier, but the overlapping with a normal control group was considerable. Only one of nine patients had no dynein arms and completely immotile cilia; an observation which renders the term "the immotile-cilia syndrome" a misnomer. The ear-nose-throat symptoms were characterized by daily nose-blowings since birth, recurrent sinusitis, and chronic secretory otitis media. On the other hand, the frequency of acute purulent otitis media and of common colds appeared to be normal.
Using a microphoto-oscillographic technique the authors studied ciliary beating of nasal epithelial cells from 11 patients with the 'immotile cilia syndrome' (Kartagener's syndrome) and from normal controls. Ciliary motility was found in all patients, except one. Although the patients had a significantly reduced number of cells with motile cilia, one-third of all ciliated cells showed motility. The beating frequency was normal, but the motility pattern was highly abnormal, with a predominance of asynchronous motility in the patients. These results suggest that the lack of dynein arms in cilia in these patients only is partial and that direct observation of ciliated cells, obtained by gentle scraping on the nasal mucosa, may be a suitable screening test for early diagnosis of this syndrome.
In a multi-centre study in which data from all Danish Hodgkin patients have been registered since 1971, all patients in supradiaphragmatic stages I or II, as confirmed by staging laparotomy, were randomized to either radiotherapy (RT) to supra- and infradiaphragmatic lymph node regions (total nodal irradiation, TNI), or RT to a mantle field followed by 6 cycles of MOPP combination chemotherapy (RT+CT). Interim results up to July 1979, when 237 patients had entered the study, showed a treatment failure rate of 19/117 in the TNI group and 4/120 in the RT+CT group (P less than 0.05). 19 of the 23 relapsing patients were under the age of 40, and 14 in the TNI group and 3 in the RT+CT group belonged to stage II. 13 patients had nodular sclerosis, 9 had mixed cellularity and 1 had lymphocytic predominance histology. 12 of 19 relapsing patients in the TNI group had hilar or mediastinal involvement as against 51 of the 117 patients in the entire group. Most of the TNI failures could be retreated, and as yet there is no difference in the overall survival.
Screening of 3060 neonates for congenital cytomegalovirus (CMV) infection by virus excretion in the urine showed an overall incidence of 0.4%. The incidence was about 1% for mothers between 16 and 25 years and only 0.2% for mothers between 25 and 35. No mothers over 35 years of age gave birth to congenitally infected infants. The percentage of women in the child-bearing age susceptible to CMV infection was estimated by the absence of CMV complement-fixing antibodies in cord sera and ranged from 48% to 33% with increasing age. None of the infected infants showed obvious signs of congenital CMV infection at birth. At follow-up, two infants showed slight, but transient symptoms compatible with a foetal infection; a pair of premature twins exhibited retarded physical and psychomotor development, but this could just as well be ascribed to the prematurity itself. None of the infants had detectable CMV--IgM antibodies in cord sera, but a trend towards elevated total IgM concentration in cord sera and elevated virus excretion titres appeared in the infants with symptoms. With the very low incidence and no signs of sensomotor sequelae the preliminary conclusion is that foetal CMV infection in our population by no means has a significance to deserve screening or a vaccination programme.
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