Dihydropyrimidine Dehydrogenase Deficiency: Metabolic Disease or Biochemical Phenotype?

Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of pyrimidine metabolism that impairs the first step of uracil und thymine degradation. The spectrum of clinical presentations in subjects with the full biochemical phenotype of DPD deficiency ranges from asymptomatic individuals to severely affected patients suffering from seizures, microcephaly, muscular hypotonia, developmental delay and eye abnormalities.We report on a boy with intellectual disability, significant impairment of speech development, highly active epileptiform discharges on EEG, microcephaly and impaired gross-motor development. This clinical presentation triggered metabolic workup that demonstrated the biochemical phenotype of DPD deficiency, which was confirmed by enzymatic and molecular genetic studies. The patient proved to be homozygous for a novel c.2059-22T>G mutation which resulted in an in-frame insertion of 21 base pairs (c.2059-21_c.2059-1) of intron 16 of DPYD. Family investigation showed that the asymptomatic father was also homozygous for the same mutation and enzymatic and biochemical findings were similar to his severely affected son. When the child deteriorated clinically, exome sequencing was initiated under the hypothesis that DPD deficiency did not explain the phenotype completely. A deletion of the maternal allele on chromosome 15q11.2-13-1 was identified allowing the diagnosis of Angelman syndrome (AS). This diagnosis explains the patient's clinical presentation sufficiently; the influence of DPD deficiency on the phenotype, however, remains uncertain.

[Health status of cattle in relation to the time of year]. / Zdravotní stav skotu ve vztahu k rocnímu období.

The periodicity of morbidity rate in heifers and dairy cows kept on pasture (278 animals) and in stables (187 animals) was studied in relation to macroclimatic conditions under the assumption of two peaks per annum. The following conditions were used as the parameters of morbidity: purulent inflammations of uterus, sterility, lesions of the female tract and sepsis, dystocia, retention of placenta, mastitis, foot diseases and lying down after parturition. No significant differences were found between the studied groups of animals. A statistically significant up to highly significant dependence was found between the health of the heifers and cows and macroclimatic conditions both in stables and on pasture; an increase in morbidity rate was recorded in spring and autumn.

[Residual larval effects of permethrin and resistance in the housefly]. / Larvální a reziduální úcinnost permethrinu a rezistence u mouchy domácí.

The effectiveness of synthetic pyrethroid permethrin in a special preparation Coopex, concentrations 0.25 and 0.5% against larval stages of housefly (Musca domestica) was tested. No larvicidal effect was proved in these commonly used concentrations. Under laboratory conditions, a very good residual effectiveness against imagoes, lasting more than 365 days (100% imago perish), was proved. In stables the residual effectiveness of Coopex was pronounced during 11 weeks. In ten generations of housefly, exposed to 0.001% concentration of Coopex, no resistance to 0.25% concentration of this substance was observed.

[Preventive and therapeutic efficacy of the vaccine against trychophytosis in cattle]. / Preventivní a lécebná úcinnost vakcíny proti trichofytóze u skotu.

The effectiveness of vaccine against dermatomycosis, caused by Trichophyton verrucosum, was studied in young cattle in three herds. The vaccines of Czechoslovak and Soviet production had almost the same effectiveness in prevention. In healthy calves without clinical signs of trichophytosis vaccinated at an age of one to three months with a dose of 2.5 to 5.0 ml, applied intramuscularly, and revaccinated with due respect to the rules of hygiene in the calf-houses, an incidence of 0 to 13% in the three- to five-month period of study was observed. In the non-vaccinated control groups, the incidence under the same infection conditions and in the same period was 36.3 to 100.0%. At the early stage of vaccination--during the inoculation of the animals suspected of being infected--the incidence of the disease was 50.0 to 68.8% and mostly showed no difference from incidence observed in the nonvaccinated control cattle. The therapeutic effect of the vaccine and Mykolastanox F is characterized by the fact that zero prevalence was obtained in the animals ten weeks after vaccination. Animals treated locally with Mykolastanox F showed zero prevalence 12 weeks after the beginning of treatment.

[Fascioliasis prevention in cloven-hoofed wild animals and animal reserves]. / Fasciolose-Bekämpfung beim Schalenwild in Wildgehegen und Tierparkanlagen.

Pilot trials are described in which BHS, a Czechoslovak fasciolicide, was employed for mass treatment of fasciolosis in cloven-hoofed animals in wild-animals' reserves at the rate of 30 mg body weight using BHS-medicated feed. The treatment was combined with control measures against the intermediate host snail, Lymnaea truncatula, in primary biotopes using Frescon, a molluscicide of English origin, and CF-4, a molluscicide of Czechoslovak origin, at concentration of 1 and 0.5 per cent, respectively. Where the application of molluscicides was impracticable the intermediate host snails were controlled by means of sciomyzid larvae or by blasting surface layers of the soil.--Using this combined approach, the extensity of infestation, evaluated on the basis of coproovoscopical examination, was reduced from 7.05 to 0.71 per cent. The extensity of infestation, evaluated on the basis of necropsy findings, was reduced from 50 to 6.2 per cent. The intensity of infestation was reduced from 7.7 to 0.31 per cent per animal.--The results may prove useful in devising fasciolosis control schemes based on a complex approach.