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Biomedical subjects

C Parkinson

Publications and source records attributed to C Parkinson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Anaerobiospirillum succiniciproducens septicaemia: important aspects of diagnosis and management.

Anaerobiospirillum succiniciproducens is a rare cause of septicaemia. A 63-year-old woman with liver cirrhosis and a history of melaena developed A. succiniciprodocens septicaemia. She owned two pet dogs and a cat. Despite supportive management and antibiotic treatment supported by in vivo testing, the patient died. The characteristics identification and antimicrobial susceptibility of A. succiniciproducens are discussed and previous reported underlying disease reviewed.

Animals↗
PubMed1997

Reproductive toxicity testing of pharmaceutical compounds to support the inclusion of women in clinical trials.

1. The potential for toxicity to reproduction and the developing fetus is an important concern requiring attention during the development of new medicines. However, there are differences in the opinions of the regulatory authorities in Europe, Japan and the USA regarding the nature and amount of data from reproductive toxicity tests that should be available at the various stages of clinical development. 2. Forty-one companies or their subsidiaries from Europe, Japan and the USA provided data for a questionnaire-based study, carried out in 1994, to ascertain the practices of pharmaceutical companies and their views on an ideal approach to the timing of reproduction and development toxicity studies in relation to clinical investigation. 3. Differences were identified in the stage of drug development at which animal studies were completed, the sequence of completion of specific studies, and the extent of reproduction testing completed to support the inclusion of women in clinical trials. 4. A harmonised, but flexible, guidelines, encompassing the timing of reproductive toxicity studies in relation to clinical trials, would permit better integration between clinical and non-clinical studies in an international drug development programme.

Animals↗
PubMed1996

The timing of preclinical toxicological studies: pharmaceutical company approaches to toxicity testing in support of initial clinical investigations.

The completion of preclinical toxicity studies to support the first administration to humans is a time-critical step in the clinical development of medicines, and is complicated by differences in national regulatory requirements. A questionnaire-based study was carried out in 1994 to ascertain pharmaceutical companies' actual practices and views on an ideal approach to the timing of different types of nonclinical safety studies in relation to clinical investigation. Forty-one companies or their subsidiaries from Europe, Japan, and the United States responded by providing data. A range of preclinical packages were indicated as being used by companies prior to initiating Phase I clinical trials. The selection of studies tended to be based on the recommendations of the regulatory authority of the region in which the respondents were located. Differences were evident regarding the extent of genetic toxicity testing, the duration of repeat-dose toxicity studies, and the need for male fertility testing to support the first single administration of a compound to humans. In an ideal situation, the respondents would have preferred to conduct shorter duration repeat-dose toxicity studies prior to the first single administration to humans than was their actual practice in 1994. A harmonized guideline on the timing of toxicity studies in relation to clinical trials will allow better integration between clinical and nonclinical studies in an international development program. However, the diversity in the responses has demonstrated the need for flexibility in any future guideline.

Animals↗
PubMed1995

The value of information generated by long-term toxicity studies in the dog for the nonclinical safety assessment of pharmaceutical compounds.

Data on 117 pharmaceutical compounds in the CMR toxicology database have been analyzed to determine what new toxicological information was provided by the dog in chronic (6 months or longer) toxicity testing. For more than half of the 117 compounds, all salient effects in the dog were seen for the first time within 3 months. For just under one-third of the compounds, any effects that occurred for the first time beyond 3 months in the dog were also seen in studies in the rat. Only 13 of the 117 compounds showed new and possibly important effects in the chronic study. No particular therapeutic class nor any other single circumstance was implicated in these 13 cases. Types of late-onset findings in the dog occurring with more than 1 compound included nonspecific effects or hypertrophic/hyperplastic changes. There may be several reasons, pragmatic as well as scientific, why it can sometimes be desirable to carry out chronic repeat-dose studies of 6 months or longer in the dog. However, the results of this retrospective evaluation have demonstrated that in the large majority of cases analyzed, long-term toxicity studies in the dog provide relatively little qualitatively new toxicological information not already gained from a short-term (3 month) study in the dog in conjunction with short- and long-term studies in the rat.

Animals↗
PubMed1994

Histopathology of localized prostate cancer. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

Future handling of patients with localized prostate cancer will undoubtedly depend upon a more sophisticated prognostication than that available today. The basis will continue to be the histopathological evaluation of tumor size, grade, localization and distribution within the gland. The aim of this section is to summarize current concepts of the morphological characteristics of localized prostate cancer and their prognostic implications as well as to give guidelines for standardization of the methods involved in morphological evaluation. First, baseline recommendations for the tissue processing procedures are given: Needle core biopsies, taken in a systematic way, potentially contain the information necessary for estimation of grade, size, distribution and extension to seminal vesicles, and could yield material for DNA-measurements, cytogenetic and genetic information. For TUR specimens it is suggested that at least 10 grams should be embedded or 8 to 10 cassettes employed minimally. The prostatectomy specimens should be carefully examined. Material should be frozen both from tumor tissue and from other areas eg by taking 'mapping' biopsies in a standardized way. After fixation (in 10% buffered formalin for at least 24 hours) and appropriate inking of surgical margins, whole mount sections at 2.5-5 mm intervals should be cut. The extension of the tumor should be outlined and at least the two largest tumors should be graded. Capsule penetration and extension to surgical margins and seminal vesicles should be indicated. Grading of malignancy should always include the Gleason grade and where possible Gleason score (ie the sum of the dominant and the secondary grade or pattern). The WHO and the Boecking systems combine a grading of glandular architecture with a grading of the nuclear atypia. It is stressed that in core biopsies the amount of cancer is sometimes scanty, which limits the possibility to find dominant and secondary patterns. In such cases, a grading of glandular differentiation and of nuclear grade seems rational. Also, for comparison with cytological grading, the WHO system is suitable, since in both cases both tissue differentiation and nuclear atypia are judged. The future need for objective techniques is recognized. Prostatectomy pathology includes important features with high correlation to postoperative prognosis: eg capsular penetration. The extent of capsular penetration and the extent of involvement of the surgical margins is of importance. Only focal penetration or focal involvement of the margin carry a relatively low risk of of progression.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers, Tumor↗
PubMed1993

The use of the dog in toxicity tests on pharmaceutical compounds.

1. The preclinical animal safety testing strategy used in pharmaceutical development is generally successful, with the large majority of new medicines not causing serious toxicity in man. The use of the dog has significantly contributed to this achievement by aiding the selection of safe compounds for human trials. 2. The dog should be selected as the non-rodent species for pharmacodynamic, pharmacokinetic, metabolic and other scientific reasons, not solely for practical considerations. 3. The dog is an extremely useful laboratory animal, particularly for procedures requiring extensive handling, detailed observation or biological sampling. 4. Refinements in the use of the dog have been achieved, but further progress is desirable. Retrospective analysis of pharmaceutical toxicity data could encourage the regulatory flexibility necessary for further progress.

Animals↗