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Biomedical subjects

T Smit

Publications and source records attributed to T Smit.

At least 19 recordsLinked to original sources

Evaluation of cisplatin and a novel platinum polymer conjugate for drug toxicity and drug distribution in mice.

The toxicity and distribution of cisplatin and two novel platinum (Pt) polymer conjugates (Pt-6 and Pt-7) were determined in serum and tissue of BALB/c mice at specific time points after i.p. administration of a drug bolus containing identical Pt concentrations. Pt concentrations were determined in serum, liver and kidney at 5 and 15 min, respectively, after drug administration by inductively coupled plasma mass spectrometry. It was found that the Pt polymer Pt-7 gave rise to a considerably lower Pt concentration in serum and considerably higher concentration in liver and kidney than cisplatin. LD25 measurements indicated that the Pt-7 polymer is considerably less toxic than cisplatin. In vitro experiments and determination of IC50 values in a variety of human tumor cell lines, normal lymphocytes and fibroblasts confirmed that Pt-6 and Pt-7 polymers are 40-500 times more toxic for tumor cells than for normal cells, perhaps reflecting preferential uptake. The toxicity of cisplatin was found to be only 1.6-40 times more effective in tumor cells. These inter-relationships are supported by the observation that the tumor enrichment factor (TEF) for cisplatin is only in the region of 6, and much lower than for Pt-6 and Pt-7, where TEFs are in the region of 40 and 150, respectively. These results demonstrate that the Pt polymer conjugates exhibit greater tumor specificity than cisplatin, killing tumor cells more effectively while being considerably less toxic for normal cells. It is concluded that the Pt polymer conjugates may be superior for cancer therapy and warrant further testing to assess their full clinical potential.

Animals↗

Vaccination in the control of bluetongue in endemic regions: the South African experience.

The eradication of bluetongue virus (BTV) from endemic regions of Africa is virtually impossible due to the role played by the widely distributed Culicoides spp. of midge vectors and the ubiquitous distribution of reservoir species. In endemic areas attempts can only be made to limit the occurrence of bluetongue (BT) disease and its economic impact through vaccination. Despite several potential problems (teratogenicity, risk of reassortment and reversion to virulence of the attenuated viral strains), epidemiological and recent molecular data support the fact that the live attenuated vaccine that has been used for decades in enzootic regions, provides a safe and efficacious means to control the disease in regions of southern Africa, as well as other areas of the world.

Animals↗

Allelic frequencies of host genetic variants influencing susceptibility to HIV-1 infection and disease in South African populations.

OBJECTIVES: Limited information is available on the prevalence in African populations of host genetic polymorphisms conferring resistance to HIV-1 infection and disease. The objective of this study was to determine the allelic frequencies in South African populations of the chemokine receptor gene variants CCR5delta32, CCR5m303 and CCR2b-641 and the CXCR4 ligand gene variant SDF1-3'A. METHOD: Cross-sectional study to determine the prevalence of these gene variants in South African subjects of African and European descent. RESULTS: The CCR5delta32 genetic variant is rare in individuals of African origin, having an allelic frequency of 0.1% (n = 1247) compared with 9.8% (n = 144) in Caucasians. The CCR5m303 mutation was not detected in Africans (n = 687), whereas an allelic frequency of 0.9% (n = 145) was identified in Caucasians. The frequency of CCR2b-641 allele was 13.1% (n = 180) in Africans, which was significantly higher that the 7.2% (n = 146) detected in Caucasians. Finally the allelic frequency of the SDF1-3'A gene variant was only 1.0% (n = 198) in Africans compared with 19.8% (n = 145) in Caucasians. CONCLUSIONS: These results indicate that genetic polymorphisms conferring resistance to HIV-1 infection are rare in the South African Black population. Except for the CCR2b-641 gene variant, individuals of African origin also had a much lower prevalence of genetic variants associated with prolonged disease progression.

Alleles↗

[Is an implant always necessary after enucleation?].

A retrospective study was performed on 114 patients who had received an intraorbital ball implant after removal of an eye: 44 had a primary implant inserted at the time of enucleation and 70 a secondary implant, inserted at a later date. We observed distinct advantages in the primary implantation group. Patients with a primary implant, an acrylic ball covered with sclera inserted within Tenon's capsule, had better cosmetic results and a lower complication rate and fewer needed any other therapeutic measures. Of the patients with primary implants 89% did not require further treatment, as against 51% with secondary implants.

Eye Enucleation↗

Clinical presentation of Graves' ophthalmopathy.

The eye findings of Graves' ophthalmopathy were prospectively recorded in 90 consecutive untreated patients (66 females, 24 males; mean age 44.5 years) according to the 1977 NOSPECS classification. Soft-tissue involvement was observed in 90%, proptosis greater than or equal to 23 mm in 30%, eye muscle involvement in 60%, corneal involvement in 9% and sight loss in 34%. No differences in the distribution of eye changes between right and left eye were found. Values for proptosis (mean +/- SD, 20.2 +/- 3.6 mm) had a near-normal distribution. Orbital computed tomography (CT) scanning (performed in 80 cases) demonstrated enlargement of inferior rectus in 60%, medial rectus in 50%, superior rectus in 40% and lateral rectus in 22%. Unilateral eye disease was present in 13 patients (14%); in 4 of these patients the CT scan showed eye muscle enlargement also in the fellow eye and in 2 patients bilateral eye disease subsequently developed. The distribution of age, sex and NOSPECS classes in patients with unilateral eye disease was similar to that in patients with bilateral eye disease, but the interval between the onset of thyroid and eye disease was much shorter in cases of unilateral than in cases of bilateral eye disease. Patients without clinically evident thyroid disease (n = 20, 22%) were not different from patients with thyroid disease in age, sex or ophthalmological presentation. The various data suggest: (1) the 1977 NOSPECS classification under-represents significant proptosis in 12% of cases; (2) the age and sex distribution of patients with Graves' ophthalmopathy is similar to that of cases with thyroidal Graves' disease, and (3) unilateral Graves' ophthalmopathy may represent an early stage of the disease, that as a rule already is or develops shortly afterwards into a bilateral disease.

Adult↗

Temporal relationship between onset of Graves' ophthalmopathy and onset of thyroidal Graves' disease.

The temporal relationship between the onset of Graves' ophthalmopathy and the onset of thyroidal Graves' disease was evaluated in 125 consecutive patients with Graves' ophthalmopathy. Thyroidal Graves' disease--past or present--was clinically evident in 99 patients (79%): hyperthyroidism in 3 cases. Thyroid disease preceded the eye disease in 37 patients, it occurred simultaneously with the eye disease in 39 patients, and it developed after the eye disease in 23 patients (in 16 cases within one yr after the onset of eye disease). The age at the onset of thyroid disease (38.7 +/- 12.9 yr) was lower than the age at the onset of ophthalmopathy (41.8 +/- 12.5 yr; p less than 0.001). Among the 26 clinically euthyroid patients (21%) laboratory evidence of thyroidal Graves' disease was found in 14 cases (11%): abnormal TRH test, n = 9; normal TRH test but abnormal T3-suppression test, n = 4; normal TRH and T3-suppression tests but positive thyroid stimulating antibodies, n = 1). We conclude that Graves' ophthalmopathy as a rule develops at a time when thyroid autoimmunity also exists. This strongly suggests a common factor in the pathogenesis of thyroidal and ocular expressions of Graves' disease.

Adult↗

Therapeutic outcome of prednisone medication and of orbital irradiation in patients with Graves' ophthalmopathy.

Response to treatment was evaluated prospectively in 58 patients with Graves' ophthalmopathy. Prednisone, administered to 44 patients, resulted in a favourable response in 29 patients (66%): excellent in 3, good in 10 and fair in 16 subjects; 15 patients (34%) did not respond. Orbital irradiation was administered to 39 patients of whom all except 4 had been treated previously with steroids. Six months later, 25 patients (64%) had responded favourably (excellent in 0, good in 9 and fair in 16 subjects) and 14 patients had not responded (36%). A favourable response to prednisone or irradiation was reflected in a general shift to lower grades in each of the classes 2-6 of the NOSPECS system. Responders were not different from non-responders with regard to age, sex, NOSPECS classification, ophthalmopathy index, interval between the onset of eye disease (or of thyroid disease if present) and the start of treatment, or the presence of thyroid disease. In conclusion, (1) the ratio of responders to non-responders is 2:1 for both prednisone treatment and orbital irradiation in Graves' ophthalmopathy, (2) the response is seen in all classes of the NOSPECS system, and (3) the response is not dependent on age, sex, severity or duration of eye disease, or the presence of thyroid disease.

Female↗

Avian tuberculosis in wild birds in the Netherlands.

Mycobacterium avium was isolated from 82 of 11,664 birds submitted for necropsy in The Netherlands. All isolated M. avium strains belonged to serotype 1, 2 or 3. The greatest number M. avium were from buzzards and falcons. The prevalence of tuberculosis in gulls is extremely low.

Animals↗

Drinking water vaccination against infectious laryngotracheitis.

Chickens varying in age from ten days to five years were vaccinated with 10(1.3), 10(2.3) and 10(3.3) EID50 per bird of a commercial infectious laryngotracheitis drinking water vaccine. The vaccine gave no adverse reaction in the dose range tested. Five weeks after administration of 10(3.3) EID50 per bird 70% were protected against the intratracheal challenge with virulent infectious laryngotracheitis virus. Doses of 10(1.3) and 10(2.3) EID50 per bird did not give protection. No serological response could be detected by the neutralization test even in the group that had received 10(3.3) EID50 per bird. No contact spread of virus was detected from 14 days post-vaccination. Carriers of vaccine virus could not be demonstrated.

Animals↗

[Bird mortality and monitoring the environment (author's transl)].

Birds are useful parameters in studying toxicological contamination of the environment. Birds can be heard and seen, breeding results and feeding patterns being recorded on a rather extensive scale in the Netherlands. Since 1974, a working party was constituted to study normal and abnormal death of birds. This group consists of members of ornithological and veterinary institutes as well as local field workers, bird revalidation centres and bird preservation and protection groups. In 1979, approximately 2,000 birds were available for post-mortem and bacteriological, virological and toxicological studies. The cases of poisoning were classified into acute and chronic, accidental and crop-protecting effects. In the Laboratory of the Central Veterinary Institute, Poultry Department, the birds suspected of poisoning are screened by a biological-toxicological standard method using Lebistes and Daphnia. Pseudo-poisoning is caused in nature by Pasteurellosis, accidents, etc. Investigations are restricted by predation, the likelihood of finding of dead birds and retention of dead birds of prey for taxidermy. Acute poisoning in the Netherlands is mostly associated with protection of crops, nuisance caused by pigeons and other birds in gardens. Some cases of poisoning are due to quarrels between neighbours and people who poison game-birds out of revenge. Chronic poisoning is caused by metals such as lead pellets from cartridges. Chronic and acute poisoning continue to occur as a result of illegal use of prohibited insecticides.

Animals↗

[Pasteurella multocida infections in birds following cat bites (author's transl)].

Infection with Pasteurella multocida caused by bites has been known for several decades. Cats are an important factor in Pasteurella multocida infection. Considerable numbers of victims are 'rescued' from the mouths of cats and submitted to bird reception centres for treatment. A number of bird shelters sent birds in this condition to the present authors for closer examination. The majority of birds caught by cats die. The mortality rates in shelters were reported to be 30, 90, 99 and one hundred per cent. Of the birds rescued alive from the mouths of cats, approximately 40 per cent died from the direct effects of the bites, and approximately 60 per cent died from Pasteurella multocida infection.

Animals↗

Local distribution of energy deposition in and around the follicles of a 125I contaminated thyroid.

Iodine-125, which is used for the clinical diagnosis of the thyroid gland, has a high probability of decay by K-capture followed by the emission of low-energy electrons having ranges of up to 23 micrometer. Thus one has high local concentrations of energy deposition comparable in size to that of the smaller follicles. In this paper the local distribution of energy deposition inside and outside the follicles of the human thyroid gland is calculated for follicle sizes of 20--400 micrometer. Also the local dose rate at the position of the nuclei of the follicle cells is determined as a function of the follicle size. Possible dosimetric approaches to the problem of radiobiological effectiveness are discussed, at first in general and then for the example of the inactivation of follicle cells due to the incorporation of 125I.

Electrons↗

[New Castle disease in imported birds. Cases observed and experimental vaccination (author's transl)].

An acute, highly virulent form of Newcastle disease is frequently observed in imported birds. Particularly parrots and, in some cases, pheasants are a potential source of danger. Diseased birds are imported from Asia as well as from South America. Outbreaks among birds imported from Africa have not so far been observed. The number of shipments in which Newcastle disease was found to be present in the birds is reviewed. Moreover, experimental vaccination is discussed.

Animals↗