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Biomedical subjects

R Billington

Publications and source records attributed to R Billington.

14 recordsLinked to original sources

Developmental toxicity evaluation of triclopyr butoxyethyl ester and triclopyr triethylamine salt in the CD rat.

Triclopyr (3,5,6-trichloro-2-pyridyloxyacetic acid) is an herbicide used extensively in the control of woody plants and broadleaf weeds, and is often formulated as a triethylamine salt (T-TEA) or butoxyethyl ester (T-BEE). This study evaluated the developmental toxicity of T-TEA or T-BEE in time-mated CD rats gavaged on gestation days 6-15 with 0, 30, 100 or 300 mg/kg body weight(bw)/day. The doses of each compound were equimolar and equivalent to 22, 76, 216 mg/kg bw/day of triclopyr, based on prior studies indicating rapid cleavage of the salt or ester and equivalent pharmacokinetics for the active ingredient. T-TEA caused maternal toxicity, evidenced by the death of one high-dose dam, reduced body weight gain, increased relative liver and kidney weights (300 mg/kg bw/day), reduced feed consumption, and increased water consumption (100 and 300 mg/kg bw/day). Developmental effects were limited to slightly decreased fetal body weight and reduced skeletal ossification at the high dose level. T-BEE caused similar, albeit slightly more severe, maternal toxicity, with three maternal deaths at 300 mg/kg bw/day, and slight maternal effects at 30 mg/kg bw/day. Due to an equivocal increase in malformations, which were mainly clustered in litters from three high dose dams with marked maternal toxicity, the T-BEE study was repeated using 30 dams/group, investigator-blind fetal evaluations, and an additional dose group (5 mg/kg bw/day). In the repeat study, the only reproducible fetal effect was an increased incidence of 14th thoracolumbar rib at 300 mg/kg bw/day. Overall analysis of the two T-BEE studies suggested that the fetal malformations unique to the initial study likely reflected a combination of spontaneous events, exacerbated by marked maternal toxicity. The combined weight of evidence from these developmental toxicity studies, coupled with their known pharmacokinetic equivalence, indicates that T-BEE and T-TEA are not selectively toxic to the fetus. The respective maternal toxicity no-observed effect levels (NOEL) for T-BEE and T-TEA were 5 and 30 mg/kg bw/day, while the NOEL for developmental toxicity was 100 mg/kg bw/day for both compounds.

Abnormalities, Drug-Induced↗

Morphoea and Borrelia burgdorferi: results from the Scottish Highlands in the context of the world literature.

AIMS: Previous studies investigating the link between infection with Borrelia burgdorferi and morphoea have produced conflicting results. Often, these studies have been undertaken in patients from different regions or countries, and using methods of varying sensitivity for detecting Borrelia burgdorferi infection. This study aimed to establish whether a relation could be demonstrated in the Highlands of Scotland, an area with endemic Lyme disease, with the use of a sensitive method for detecting the organism. METHODS: The study was performed on biopsies of lesional skin taken from 16 patients from the Highlands of Scotland with typical clinical features of morphoea. After histological confirmation of the diagnosis, a nested polymerase chain reaction (PCR) using primers to a unique conserved region of the Borrelia burgdorferi flagellin gene was performed on DNA extracts from each biopsy. A literature search was also performed for comparable studies. RESULTS: None of the 16 patients had documented clinical evidence of previous infection with B burgdorferi. DNA was successfully extracted from 14 of the 16 cases but all of these were negative using PCR for B burgdorferi specific DNA, despite successful amplification of appropriate positive controls in every test. The results were compared with those of other documented studies. CONCLUSIONS: Examination of the literature suggests that there is a strong geographical relation between B burgdorferi and morphoea. These results, in which no such association was found, indicate that morphoea may not be associated with the subspecies of B burgdorferi found in the Highlands of Scotland.

Adolescent↗

The WHO quality of life assessment instrument (WHOQOL-Bref): the importance of its items for cross-cultural research.

One of the fundamental issues in the area of assessment of quality of life is to determine what is important to the individuals' quality of life. This is even more crucial when the instrument is for use in diverse cultural settings. This paper reports on the importance ratings on WHOQOL-Bref items obtained as a part of WHOQOL pilot field trial on 4804 respondents from 15 centres from 14 developed and developing countries using 12 languages. All items were rated as moderately or more important, but this was expected because the items were selected by extensive qualitative research for their salience across the centres. Significant differences on mean importance ratings were found between centres, but rank orders of item for their importance showed highly significant correlations between centres. This was especially true for items in the top and the bottom thirds of the item list arranged by overall importance. Most items were rated as more important by women compared to men and by younger compared to older persons. The results are discussed for their relevance in cross-cultural research on quality of life assessment.

Adolescent↗

Setting of acute reference doses for pesticides based on existing regulatory requirements and regulatory test guidelines.

Reference doses (RfD) for the definition of tolerable food residues have traditionally been based on the lowest no observed adverse effect level (NOAEL), which usually comes from chronic toxicity studies. While this is generally agreed to be a safe approach to evaluate the overall significance of expected consumption it is clear that it is not appropriate for evaluation of the toxicological significance of residues in a single meal. Standard acute toxicity tests are not designed to generate an NOAEL, from which an RfD can be derived. They are more appropriate to evaluating risk following accidental high exposure to the product itself rather than to food residues. A typical toxicological database for a pesticide active substance contains studies which may be appropriate, on a case-by-case basis, to evaluate shorter term endpoints of interest for specific molecules, such as developmental or acute neurotoxicity studies. However, their specificity limits their scope of application. General toxicological endpoints are well covered by short-term, 28- or 90-day, guideline studies. However, neither of these studies is ideal for setting of an acute RfD (ARfD) as the treatment period is significantly longer than the duration of consumer exposure. This could be balanced by applying a reduced safety factor to the NOAEL to set the ARfD. Alternatively, a test guideline could be designed to generate a relevant acute NOAEL but the time necessary for development, validation and acceptance of such a guideline means that an interim approach is, in any case, necessary.

Animals↗

Do object relations deficits distinguish BPD from other diagnostic groups?

Two independent samples that met DSM-III criteria for borderline personality disorder (BPD) were found to have similar patterns of object relations deficits as measured by group means and percentage of high scoring subjects on the four subscales of the Bell Objects Relation (OR) Inventory. Statistical comparison of the composite BPD group with affective, schizoaffective, and schizophrenic groups revealed that the pattern of OR deficits in BPD was significantly different from each of the other diagnostic groups. On the basis of scores from the Alienation subscale alone, BPD subjects could be distinguished from the other diagnostic groups with 77-82% predictive accuracy. The role of object relations deficits in BPD is discussed, along with potential contributions of the Bell OR Inventory to diagnostic efficiency.

Adult↗

Object relations ego deficits in bulimic college women.

Two types of bulimic (purging and restricting) and two types of non-bulimic (binging or normal) eating patterns were reported by 547 undergraduate women who also were assessed for ego function deficits on the four subscales of the Bell Object Relations Inventory. As predicted by psychoanalytic theory, the two bulimic subgroups appeared significantly more pathological on the Insecure Attachment subscale, which identifies ambivalent interpersonal relations and fear of object loss. When the four groups were ranked according to severity of type of eating disorder, a linear increase in group means and in the proportion of high scoring subjects was found on Insecure Attachment and also on the Egocentricity subscale, which indicates suspicious and manipulative attitudes toward others. Results are interpreted to support theories that relate eating disorders to disturbances in object relations ego functioning.

Adolescent↗

A scale for the assessment of object relations: reliability, validity, and factorial invariance.

Factor analysis of the Bell Object Relations Inventory items produced four subscales interpreted to be underlying dimensions of object relations. Replication factor analysis confirmed the factor structure. Subscales had high internal consistency and were free of age, sex, or social desirability response bias. Subscales had low intercorrelations with Brief Psychiatric Rating Scale (BPRS) sum scores, Global Assessment Scale scores, and most BPRS symptoms. Subscales appear to represent common features of personality and to sample a domain that is distinct from symptomatology, but related to variations in psychopathology. Percentage of high scoring subjects and subscale mean values are compared for seven criterion groups. High scores were least frequent among community active adults and most frequent among borderlines. Selected findings from the group comparisons are discussed to illustrate the potential of the instrument for empirical examination of theoretical assumptions about the object relations ego function and its components.

Adult↗

Studies on nucleic acids in lymphocytes of chronic lymphocytic leukaemia.

The resting lymphocytes of patients with chronic lymphocytic leukaemia (CLL) contain the same amount of RNA as do those of normal individuals, and in terms of different molecular species, as analyzed by polyacrylamide gels, there is very little to distinguish the leukaemic cells. However, a relatively large amount of low molecular weight RNA, similar to the SnRNA found in several other tissues, is present in the CLL cells. The products of transcription of the leukaemic cell nucleus have been studied by the incorporation of labelled uridine and methionine. The leukaemic lymphocytes show a build-up and apparent delay in processing of ribosomal RNA precursor, when compared to normals, but studies of methylation reveal that the production of mature ribosomal RNA occurs at a normal rate. The nature of the stable high molecular weight material produced is now being studied. The production of proteins on the ribosome of CLL cells seems likely to be faulty, as evidenced by the deficiency of active ribosomes in the leukaemic cells. Studies with selective inhibitors will show whether this is due to some fault in transcription of messenger RNA.

Electrophoresis, Polyacrylamide Gel↗