Biomedical subjects

Paul D Kerr

Publications and source records attributed to Paul D Kerr.

4 recordsLinked to original sources

PubMed2006

Structure-activity studies with cytotoxic anthrapyrazoles.

Anthrapyrazoles have been investigated as cancer chemotherapeutic agents. The mechanism of action of these compounds is thought to involve inhibition of DNA topoisomerase II. A structure-activity study was carried out to determine the in vitro cytotoxic activity of nine novel anthrapyrazoles against human breast carcinoma, head and neck squamous cell carcinoma and leukemia cells, and against Chinese hamster ovary cells. The activity of these anthrapyrazole analogues was compared with that of two clinically tested anthrapyrazoles, losoxantrone and piroxantrone. Inhibition of topoisomerase II as a mechanism of action for the analogues was also investigated. The cytotoxic activity of the analogues was determined in vitro by MTT cell growth inhibition assay and inhibition of catalytic topoisomerase II activity by each compound was measured using a fluorometric DNA decatenation assay. All of the anthrapyrazole analogues inhibited the growth of the four cell lines with IC50 values that ranged from 0.1 to 45.2 microM. Losoxantrone was the most potent of the anthrapyrazole analogues studied. A tertiary amine in the basic side chain at N-2 increased the cytotoxic activity compared with a secondary amine in this side chain for many of the analogues, but not if there was a basic side chain at the C-5 position. A chlorine substituent on the basic side chain at N-2 did not have a consistent effect on activity. Moving the position of a chlorine substituent from C-5 to C-7 or introducing a basic side chain at C-5 did not have a consistent effect on cytotoxic activity. Anthrapyrazole analogues showed a broad range of activity for inhibiting topoisomerase II decatenation activity. Losoxantrone and piroxantrone were the most potent inhibitors of topoisomerase II activity. There was no significant correlation between the cytotoxic activity of the anthrapyrazole analogues and their ability to inhibit decatenation by topoisomerase II.

Animals↗

PubMed2005

Role of NQO1 polymorphisms as risk factors for squamous cell carcinoma of the head and neck.

A case: control study was carried out to determine if inactivating polymorphisms of the NQO1 gene at bases 609 and 465 are associated with altered risk of developing squamous cell carcinoma of the head and neck (SCCHN). Genotyping was carried out by PCR RFLP analysis on whole blood samples. The frequency of the inactive 609T and active 609C forms, and the inactive 465T and active 465C forms, of NQO1 were compared in patient and control groups by a logistic regression analysis and odds ratios (ORs) were calculated. Participants were stratified by tobacco and alcohol use, and genotype distributions in these sub-groups were compared. There were no significant differences in genotype distribution between SCCHN patients and the control population for the base 609 or 465 polymorphisms. There were also no significant differences in genotype distributions between patient and control groups for tobacco and/or alcohol users and non-users. Genotype distributions were similar for SCCHN patients at all disease sites with the exception of the nasopharynx where there was a higher incidence of the 609C:609T and 609T:609T genotypes. These results suggest that individuals having either 609T or 465T alleles generally do not have an altered risk of developing SCCHN.

Adult↗

PubMed2003

Parathyroid hormone: an early predictor of postthyroidectomy hypocalcemia.

OBJECTIVE: To determine whether there is a correlation between the level of parathyroid hormone (PTH) soon after thyroidectomy and the development of hypocalcemia. STUDY DESIGN: Prospective series of 40 consecutive patients undergoing total thyroidectomy or completion thyroidectomy between January 2001 and October 2002. METHOD: Ionized calcium was measured before surgery and at 1, 6, 18, 30, and 42 hours after surgery. PTH was measured before surgery and at 1 and 6 hours after surgery using an assay that accurately measures low levels of PTH. Patients were followed up at 1 week and 3 months after surgery with respect to their symptoms and need for calcium supplementation. Clinically significant hypocalcemia was defined as an ionized calcium level of less than or equal to 0.9 mmol/L. RESULTS: The incidence of postoperative hypocalcemia was 30% (12/40). The mean PTH level 1 hour after surgery was much lower in patients who ultimately became hypocalcemic than in those who remained normocalcemic (3.8+/- 1.9 vs. 33 +/- 21 pg/mL, P =.001). All patients with a PTH level less than or equal to 8 pg/mL 1 hour after surgery developed hypocalcemia, whereas all those with greater than or equal to 9 pg/mL remained normocalcemic. CONCLUSIONS: A single PTH level of less than or equal to 8 pg/mL 1 hour postthyroidectomy is a strong predictor for the development of clinically significant hypocalcemia. Once validated, this test may serve to identify those who require more intensive monitoring, prompt early therapy in those deemed at risk, and enable confident early discharge in the majority of thyroidectomy patients.

Age Factors↗

PubMed2002

Paranasal sinus teratocarcinosarcoma with intradural extension.

Teratocarcinosarcoma, although a rare neoplastic entity, should be considered as a differential diagnosis in any middle-aged adult presenting with a history of intermittent unilateral epistaxis and nasal obstruction. Tissue biopsy may fail to reveal a full spectrum of histologic heterogeneity in these tumours, and definitive diagnosis is usually made with tumour resection. Aggressive treatment including surgery followed by adjuvant radiation therapy is advocated and confers a better rate of survival than radiotherapy alone. Our current report is unique in two respects. First, disease recurrence is usually manifested very early on, leading some authors to conclude that a neoplastic-free interval of 3 years or longer probably indicates a good chance of being cured. Our patient, in contrast, experienced a disease-free interval of 4 years before evidence of recurrence emerged. Second, intracranial extension with brain parenchymal involvement has not been previously reported despite the tumour's proximity to the anterior cranial fossa and its locally aggressive behaviour with frequent bony invasion. Despite intracranial invasion, our patient experienced a long disease-free interval. As such, even advanced disease should be treated aggressively.

Brain Neoplasms↗