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Biomedical subjects

D van Thiel

Publications and source records attributed to D van Thiel.

14 recordsLinked to original sources
PubMed1993

Computer-guided concentration-controlled trials in autoimmune disorders.

A randomized concentration-controlled clinical trial (RCCCT) is an alternate experimental design to the standard dose-controlled study. In a RCCCT, patients are randomly assigned to predefined plasma or blood drug concentration ranges (low, medium, and high). With the caveat that concentration ranges are sufficiently separated, this design should enhance the ability to discover important concentration response relationships. FK-506, a potent and promising immunosuppressive agent for prevention and treatment of graft rejection, has shown significant clinical activity in some immune-mediated disorders. To implement the RCCCT design, a novel FK-506 intelligent dosing system (IDS) was used to guide all doses to prospectively achieve the target concentration range specific in the study protocol. Patients enrolled in these trials suffered from a variety of autoimmune disorders, including multiple sclerosis, primary biliary cirrhosis, psoriasis, autoimmune chronic active hepatitis, and nephrotic syndrome. We observed excellent predictive performance of the IDS for all patients. The accuracy (mean prediction error) of the IDS was -0.022 ng/ml and the precision (standard deviation of the prediction error) was 0.119 ng/ml. Thus, the IDS is both accurate and reproducible for autoimmune patients. We conclude that the RCCCT design, guided by an accurate and precise IDS, is an informative and cost-effective approach for evaluation of efficacy and safety of effective but highly toxic agents.

Autoimmune Diseases↗
PubMed1985

Iodine deficiency, hypothyroidism, and endemic goitre in southern Tanzania. A survey showing the positive effects of iodised oil injections by TSH determination in dried blood spots.

UNLABELLED: The Ukinga and Uwanji regions, located in the southern highlands of Tanzania, were studied for the degree of iodine deficiency and the incidence of goitre and hypothyroidism, respectively. A urinary iodine excretion as low as 17.6 +/- 9.3 micrograms/g creatinine was observed in Wangama village. The mean goitre prevalence in 27 villages in Uwanji ranged between 65 and 96% (n = 3031 schoolchildren). Of 681 pregnant women from Ukinga 79.6% had goitre. The prevalence of cretinism as estimated on clinical criteria was 3% in Magoye (Uwanji). A normal serum TSH (below 2.1 mU/l) was observed in only 12 out of 66 school children before iodine prophylaxis, whereas the T4/TBG ratio was decreased in 36 of 63 cases. Blood spot TSH levels in newborn infants (n = 219) from mothers without iodine supplementation were above 12 mU/l in 45%. In contrast, only 20.3% of the newborn (n = 118) had elevated blood spot TSH (p less than 0.002) when the mothers had received an iodised oil injection during pregnancy. Most of the newborn (n = 18; 75%) of the latter group with elevated TSH (n = 24) came from mothers who had received the iodine injection only 1-25 days before delivery. Maternal iodine prophylaxis in late pregnancy does not increase the rate of neonatal hypothyroidism. CONCLUSIONS: It has been confirmed that severe iodine deficiency resulting in endemic goitre, cretinism, and hypothyroidism is prevalent in the regions studied. Dried blood spot TSH determinations may serve as an index for the efficiency of iodine prophylaxis programmes. Such a programme was carried out with relatively little expenditure and effort on a large scale basis.

Adolescent↗
PubMed1984

Successful small bowel allotransplantation in dogs with cyclosporine and prednisone.

Twelve dogs had transplantation of almost the entire small intestine in the orthotopic location; immunosuppression was with cyclosporine and prednisone. Half the dogs had survival of at least one month, and a third lived for at least four months. Two of the animals are still living after 550 and 555 days. Maintenance of nutrition, and absorption of D-xylose and fat were better than in control animals with an iatrogenic short gut syndrome, but distinctly worse than that of normal dogs.

Animals↗
PubMed1983

[Comparison of three quality control investigations on radioimmunological determination of thyrotropin using the "Munich model"].

The results of a thyrotropin external quality assessment survey (EQAS) carried out in 1980 using the "Munich Model" and including a "matched reagent" experiment are presented and are compared with the results from similar surveys carried out in 1974 and 1977. Despite the fact that in 1974 only 4 different kits were used, compared with 12 in 1977 and 17 in 1980, the inter-laboratory precision has continually improved. This was reflected by the inter-laboratory coefficient of variation (CV) for all laboratories, which, for a sample with ca. 15 microU/l thyrotropin were: 65% (1974), 22% (1977) and 12% (1980), and for a sample containing ca. 5 microU/l thyrotropin: 75% (1974), 45% (1977) and 20% (1980). During the same period, the fraction of participants using commercial kits increased from 0.65 to 0.95. There was a definite trend towards shorter assays, even though with such assays there is a danger that the measured values for low thyrotropin concentrations will be too high. In spite of the fact that the "high-blank" effects have to a large extent disappeared, many kits showed an unacceptably high cross-reactivity with human chorionic gonadotropin. A fraction of 0.30 of all participants in 1974 used computer-assisted data-processing, compared with 0.78 in 1980. In 1980, the most commonly used algorithm was a spline function (0.46 of participants using a computer for data-processing). Although the number of kits has increased, the precision has improved, showing that more robust methods are now employed. This has partly come about because of the introduction of human thyrotropin-free serum as matrix for the standards (1974 - 0.16, 1980 - 0.83 of all participants). Further external quality assessment programmes are discussed for the continual monitoring of hormone assay performance.

Humans↗
PubMed1980

[Development of a radioimmunoassay for thyrotropin (TSH) in dried blood spots together with a comparison of 7 commercial kits (author's transl)].

The blood-spot thyrotropin RIA for detection of congenital hypothyroidism has been established as a screening programme. This article describes the problems in hand, namely optimisation of the method and a comparison of the performance in 7 commercial kits on the West German market. The following factors have been investigated: a. Shelf-life of standards and samples b. Effect of filter paper quality and weight c. Size of paper disc d. Blood sampling time e. Time of removal of paper disc f. Effect on the results of washing the precipitate. The commercial kits at present on the market differ widely in method and price. Apart from this, there was no agreement between the results obtained, and the difference between the standard concentration given by the firm compared with the reference standard MRC 68/38 varied from 22--185%. Methodological guidelines and quality control measures, both internal and external, are suggested.

Blood Specimen Collection↗
PubMed1979

[Oral immunization of newborn infants against pertussis].

A group of 148 newborn babies was subdivided into four groups. Subsequent to after oral application of killed pertussis bacteria (1-3 times; control) all developed agglutinating resp. precipitating antibodies. There was a clear relation between the given quantity of Oral Pertussis Vaccine and the antibody titer. The problem has been discussed, whether it will be possible to get a protection of newborn children against whooping cough within the first weeks of life and, simultaneously, to avoid side effects.

Administration, Oral↗
PubMed1976

[Chronic posttraumatic osteomyelitis. Attempt at oral autovaccine therapy].

18 patients suffering from chronic posttraumatic osteomyelitis were treated by oral autovaccination. 11 patients showed significant improvement of clinical condition. The therapeutic effect was evaluated by a scoring system considering the wound morphology, the bone radiology and the erythrocyte sedimentation rate. The most pronounced clinical improvements were observed in patients with established delayed type hypersensitivity against staphylococci.

Administration, Oral↗
PubMed1976

[Chronic posttraumatic osteomyelitis. Clinical aspects and bacteriology].

50 patients suffering from chronic posttraumatic osteomyelitis were examined. In 66% an open fracture, caused either by traffic or industrial accidents was the primary reason for hospitalization. The most frequent pathogenic bacterium was staphylococcus aureus: 80% of the patients suffered from staphylococcal infections, mostly, however, in mixed culture with pseudomonas aeruginosa or clebsiella. Whereas the peripheral leukocyte count and the serum electrophoresis showed abnormal values only in a small percentage of the patients, the erythrocyte sedimentation rate proved to be a reliable index of the intensity of chronic infection.

Accidents, Occupational↗