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Biomedical subjects

J Nixon

Publications and source records attributed to J Nixon.

At least 55 records · Page 3Linked to original sources
PubMed1997

Interstitial deletion of 2q associated with craniosynostosis, ocular coloboma, and limb abnormalities: cytogenetic and molecular investigation.

We report on the clinical and cytogenetic findings in a 9-year-old boy with a de novo deletion of 2q, shown by molecular analysis to have arisen from the paternal chromosome. Examination of microsatellite markers indicated deletion of bands 2q24.3 and 2q31. Clinical findings included craniosynostosis, bilateral ocular colobomata, and limb abnormalities, the latter being an emerging association with deletion of this region of 2q.

Abnormalities, Multiple↗
PubMed1997

Metastatic breast cancer 42 years after bilateral subcutaneous mastectomies.

Subcutaneous mastectomy has a possible role as prophylaxis in patients at high risk of developing breast cancer. A case history is presented of a woman who developed metastatic breast carcinoma 42 years after bilateral subcutaneous mastectomies for non-malignant disease. This case is presented to draw attention to the persistent risk of developing breast cancer even decades after subcutaneous mastectomy and to point out that the role of such surgery in preventing breast cancer has still not been clarified. The appropriateness of prophylactic mastectomy for an individual is better assessed on the absolute risk of breast cancer developing over a defined period rather than the relative risk.

Aged↗
PubMed1995

Binding of histone H1 to DNA is indifferent to methylation at CpG sequences.

The possibility that histone H1 binds preferentially to DNA containing 5-methylcytosine in the dinucleotide CpG is appealing, as it could help to explain the repressive effects of methylation on gene activity. In this study, the affinity of purified H1 for methylated and non-methylated DNA sequences has been tested using both naked DNA and chromatin. Based on a variety of assays (bandshifts, filter-binding assays, Southwestern blots, and nuclease sensitivity assays), we conclude that H1 has no significant preference for binding to naked methylated DNA. Similarly, H1 showed the same affinities for methylated and non-methylated DNA when assembled into chromatin in a Xenopus oocyte extract. Thus potential cooperative interaction of H1 with polynucleosomal complexes is not enhanced by the presence of DNA methylation.

Animals↗
PubMed1995

Resistance mechanisms determining the in vitro sensitivity to paclitaxel of tumour cells cultured from patients with ovarian cancer.

Paclitaxel, a drug which stabilises microtubules, demonstrates marked activity against ovarian cancer. We investigated the sensitivity to paclitaxel of tumour cells from disaggregated solid tumours or tumour-bearing ascites from 7 ovarian cancer patients, and 21 established tumour cell lines (ovarian, melanoma and lung). Response was quantitated by [3H]-thymidine incorporation in 96-well plates or by colony growth. Dose-response curves to paclitaxel were biphasic with a dose-dependent phase providing an IC50 value (50% reduction in incorporation) and dose-dependent "plateau" phase where the effect was independent of paclitaxel concentration. IC50 values ranged from 2.5 to 110 nM with evidence of multidrug resistance in the two most resistant cell lines. The "plateau" killing values varied from 0.1 log10 to > 3.4 log10 units reduction, and were found to be significantly correlated (r = 0.86; P < 0.0001) with logarithmic culture doubling times of the cell lines. Cellular glutathione levels were measured and found not to be significantly associated with response to paclitaxel. The results suggest that the ratio of paclitaxel exposure time to the culture doubling time is a major factor in paclitaxel cytotoxicity. The relationship between tumour cell cytokinetics and paclitaxel pharmacokinetics in vivo may therefore be crucial in determining clinical paclitaxel response.

Adult↗
PubMed1994

Effectiveness of bicycle helmets in preventing head injury in children: case-control study.

OBJECTIVE: To examine the risk of injury to the head and the effect of wearing helmets in bicycle accidents among children. DESIGN: Case-control study by questionnaire completed by the children and their carers. SETTING: Two large children's hospitals in Brisbane, Australia. SUBJECT: 445 children presenting with bicycle related injuries during 15 April 1991 to 30 June 1992. The cases comprised 102 children who had sustained injury to the upper head including the skull, forehead and scalp or loss of consciousness. The controls were 278 cyclists presenting with injuries other than to the head or face. A further 65 children with injuries to the face were considered as an extra comparison group. MAIN OUTCOME MEASURES: Cause and type of injury, wearing of helmet. RESULTS: Most children (230) were injured after losing control and falling from their bicycle. Only 31 had contact with another moving vehicle. Children with head injury were significantly more likely to have made contact with a moving vehicle than control children (19 (19%) v 12 (4%), P < 0.001). Head injuries were more likely to occur on paved surfaces than on grass, gravel, or dirt. Wearing a helmet reduced the risk of head injury by 63% (95% confidence interval 34% to 80%) and of loss of consciousness by 86% (62% to 95%). CONCLUSIONS: The risk of head injury in bicycle accidents is reduced among children wearing a helmet. Current helmet design maximises protection in the type of accident most commonly occurring in this study. Legislation enforcing helmet use among children should be considered.

Accidents, Traffic↗
PubMed1994

Radiosensitivity of new and established human melanoma cell lines: comparison of [3H]thymidine incorporation and soft agar clonogenic assays.

Seven new low-passage melanoma lines were developed in this laboratory from clinical melanoma specimens and characterised for chromosome complement, DNA ploidy and S-phase content. The radiosensitivity of these lines was compared with that of eight established melanoma cell lines, FME, MM-96, SK-MEL-5, SK-MEL-28, SK-MEL-2, MALME-3M, M19-MEL and LOX-IMVI, using a 96-well microculture assay technique. Dose-response curves were determined using a 5-day incubation period and 6-h terminal [3H]thymidine-labelling period. Radiation (60Co source) was carried out under a lead wedge to provide a radiation dose range of 0-10 Gy, or by irradiating part of the plate (radiation dose 0 or 2 Gy). Data for a range of cell densities in a single 96-well plate were combined into a single regression equation incorporating linear quadratic terms for radiation dose and cell density. SF2 values were defined as the amount of thymidine incorporated following a radiation dose of 2 Gy, expressed as a fraction of that of unirradiated cells, and varied from 0.36 to 0.93. The reproducibility in repeat assays, as defined by the standard error of determinations at different passage numbers, was +/- 0.04. The newly developed lines exhibited a similar range of radiosensitivity to that of the established lines, and melanin content did not correlate with resistance. For nine of the lines, radiation parameters were also determined using a modified Courtenay clonogenic soft agar assay technique, and the results compared with the thymidine incorporation results, and a significant linear correlation was found between SF2 and SF2' (r = 0.89). The linear (alpha) and quadratic (beta) terms of the best-fit linear quadratic dose-response curves, were significantly correlated between the two assays. It is concluded for this series of human melanoma lines that proliferation assays in 96-well plates provide radiosensitivity parameters comparable to those using clonogenic assays.

Adult↗
PubMed1994

Child injury in Brisbane South 1985-91: implications for future injury surveillance.

Specific childhood injury types are ranked by occurrence rate for mortality, hospital admission and emergency department attendance. Cases are drawn from the resident population of Brisbane South, 0-13 years of age, for the period 1 July 1985 to 30 June 1991. A total of 47,244 injuries, 7056 admissions and 99 deaths were analysed. The overall mortality rate was 12.6/100,000 per year (95% confidence interval (CI), 10.2-15.3), the overall admission rate was 911/100,000 per year (95% CI, 890-932) and the overall hospital attendance rate was 6013/100,000 per year (95% CI, 5958-6067). A fall was the most frequent injury mechanism for admissions and 65% of attendances involved injury in the child's own home. The surveillance data establish regional variation for childhood injury risk within Australia and identify an unexplained downward trend in head injury that requires further investigation. The future development of injury surveillance in Australia requires simplified coding which can be integrated into new computerized patient management information systems.

Accidents↗
PubMed1992

Microculture-based chemosensitivity testing: a feasibility study comparing freshly explanted human melanoma cells with human melanoma cell lines.

BACKGROUND: The culture of cancer cells has many applications in chemosensitivity testing and new drug development. PURPOSE: Our goal was to adapt simple semiautomated microculture methods for testing the chemosensitivity of melanoma cells freshly recovered from patients' tumors. METHODS: Cells were cultured on a substrate of agarose and exposed continuously to cytotoxic drugs, the effects of which were measured by determining the uptake of [3H]thymidine 4-7 days later. RESULTS: Immunocytochemical staining of cells cultured with 5-bromo-2'-deoxyuridine demonstrated that tumor cells were responsible for the measured thymidine incorporation. The effects of cytotoxic drugs were calculated as logarithmic 50% inhibitory concentrations and expressed as divergences from the mean in a log-mean graph. The inhibitory effects of amsacrine, etoposide, doxorubicin, cisplatin, mitomycin C, and fluorouracil were tested. Tumors differed widely in their sensitivity to these drugs, although sensitivity to the three topoisomerase-II-directed agents was highly correlated. Cells from two non-neoplastic hematopoietic progenitor cell lines (FT and 32D) showed chemosensitivity patterns distinct from those in the melanoma cells, indicating tissue selectivity. Two established melanoma cell lines, MM-96 and FME, were tested under the same conditions and showed sensitivity typical of at least some fresh specimens. CONCLUSIONS: These results support the validity of melanoma cell lines as models of freshly resected melanoma cells. If successfully applied to other tumor types, such semiautomated approaches could find wide application in routine hospital laboratories for the chemosensitivity testing of patients' tumor cells.

Animals↗
PubMed1991

Attitude, anxiety, and social readjustment toward learning disabilities by student teachers.

84 student teachers from undergraduate classes at a western university in Kansas completed a 9-question checklist of learning disabilities before interacting with a behavioral disordered/learning disabilities teacher, a paraprofessional, and a high school learning-disabled student. After the dialog, the student teachers completed a Social Readjustment Rating Scale, Breskin Rigidity Test, the Self-evaluation Questionnaire: State and Trait Anxiety, and the same 9-question checklist with one additional question ("Now that you have seen a learning-disabled student has it affected your opinion of learning disabilities?"). The dialog affected 63% of the students' opinions while 31% stated the presentation did not affect their opinion (6% were missing or not completed). Persons who experienced more life-changes and problems tended to rate or view learning disabilities more negatively. The more trait anxiety experienced by the students, the lower they rated learning disabilities after the presentation.

Adolescent↗
PubMed1990

Platelet-derived growth factor and its receptor in blood cell differentiation and neoplasia.

Platelet-derived growth factor (PDGF) is a family of dimeric protein molecules synthesized by differentiated, non-dividing and proliferating blood cells. Experimental findings indicate that PDGF is involved in development and/or maintenance of physiological functions of certain normal blood cells. Also, PDGF synthesis correlates with certain blood cell proliferative diseases caused either spontaneously or associated with viral infection. There is increasing evidence that the diverse effects of PDGF in both normal and abnormal physiological functions of blood cells may be regulated at the level of its receptor. New experimental findings are discussed relating to PDGF receptors in normal leukemic, and virally-infected human cells of myeloid and lymphocytic lineages. At specific developmental stages this regulation may take the form of PDGF and its receptor being expressed or co-expressed; the unmodified or modified form of receptor that specifically interacts with PDGF; the cellular site at which the PDGF-receptor interacts with its ligand; and co-expression of the PDGF-receptor with other receptors associated with specific cell lineage or functions. Elucidation of events involved in synthesis, processing, and interactions of PDGF isoforms and their respective receptors will enable us to develop pharmacological means that may either interfere with, or enhance these desired blood cell functions. This review focuses on PDGF and its receptor in human blood cell differentiation and neoplasia.

Blood Cells↗
PubMed1990

The role of dacryocystography in the management of patients with epiphora.

A retrospective study has been carried out on 114 patients who have undergone dacryocystography (DCG) for epiphora, to assess the role of DCG in their management. It was found that 16/66 (24%) patients who were offered surgery after DCG refused it or were assessed as unfit for surgery, demonstrating the need for careful counselling and assessment of patients prior to investigation. The presence of lacrimal system obstruction on DCG was an important factor in determining whether a patient underwent lacrimal surgery. However, the actual level of the obstruction influenced neither the likelihood of a patient undergoing lacrimal surgery nor the form of lacrimal surgery undertaken. This suggests that, unless the surgical approach will be modified in the light of the anatomical information furnished by DCG, DCG is not necessary. Lacrimal scintigraphy would provide sufficient information for the practical management of epiphora. Syringing of the lacrimal system correlates poorly with DCG in detecting obstruction.

Dacryocystorhinostomy↗
PubMed1988

Disease relapse in patients with stage I nonseminomatous germ cell tumor of the testis on active surveillance.

Thirty-six patients with apparent stage I nonseminomatous germ cell tumor (NSGCT) of the testis were treated by inguinal orchidectomy and intensive follow-up only. Assessment included measurement of serum alpha fetoprotein (alpha FP) and beta human chorionic gonadotropin (beta HCG) (tumor markers) and chest x-ray monthly for 1 year, then twice monthly for 1 year, with computed tomographic (CT) scans of abdomen and chest repeated three times monthly for the first year and six times monthly for the second year. Median follow-up was 36 months (range, 14 to 92 months). Relapse occurred in 12 patients (33.3%) at a median of 7 months (range, 2 to 28 months). Elevated markers were of limited importance in relapse detection, confirming the need for close clinical and radiological follow-up. Of nine histological factors examined in the primary tumor only the presence of lymphatic invasion was associated with a significantly higher relapse rate. All patients were treated at relapse with cisplatin-based chemotherapy. Four underwent surgery in addition, two before and two after chemotherapy. Eleven were rendered disease-free, but four had a second relapse. One patient has died, one is alive with disease, and ten are disease-free. Chemotherapy failed to cure six patients who had relapsed but bulk of disease was not a factor. Despite the good overall result reported here, optimal postorchidectomy management of apparent stage I disease remains to be defined.

Adolescent↗